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Introduction: Microsoft Kinect V2® (Kinect) is a peripheral device of Xbox® and acquires information such as depth, posture, and skeleton definition. In this study, we investigated whether Kinect can be used for human gait analysis. Methods: Ten healthy volunteers walked 20 trials, and each walk was recorded by a Kinect and infrared- and marker-based-motion capture system. Pearson’s correlation and overall agreement with a method of meta-analysis of Pearson’s correlation coefficient were used to assess the reliability of each parameter, including gait velocity, gait cycle time, step length, hip and knee joint angle, ground contact time of foot, and max ankle velocity. Hip and knee angles in one gait cycle were calculated in Kinect and motion capture groups. Results: The coefficients of correlation for gait velocity (r = 0.92), step length (r = 0.81) were regarded as strong reliability. Gait cycle time (r = 0.65), minimum flexion angle of hip joint (r = 0.68) were regarded as moderate reliability. The maximum flexion angle of the hip joint (r = 0.43) and maximum flexion angle of the knee joint (r = 0.54) were regarded as fair reliability. Minimum flexion angle of knee joint (r = 0.23), ground contact time of foot (r = 0.23), and maximum ankle velocity (r = 0.22) were regarded as poor reliability. The method of meta-analysis revealed that participants with small hip and knee flexion angles tended to have poor correlations in maximum flexion angle of hip and knee joints. Similar trajectories of hip and knee angles were observed in Kinect and motion capture groups. Conclusions: Our results strongly suggest that Kinect could be a reliable device for evaluating gait parameters, including gait velocity, gait cycle time, step length, minimum flexion angle of the hip joint, and maximum flexion angle of the knee joint.

Introduction: Trochanteric femoral fracture is one of the most common fractures in the elderly. Trochanteric femoral fracture with involvement of the lesser trochanter is considered unstable and recognized as having a poor prognosis. However, fixation of lesser trochanter fragment is scarce because of technical difficulties. In this study, we reported the simple surgical procedure and the effect of using nonabsorbable tape in lesser trochanter fixation. Methods: From January 2014 to December 2017, 114 patients treated with proximal intramedullary nailing for trochanteric fractures with the lesser trochanter fragment were reviewed. Among patients enrolled in this study, 73 were followed up until radiographic bone union, of which 26 were treated with lesser trochanter fragment banding (group B) and 47 without banding (group N). Radiographs and/or computed tomography images were used to evaluate bone union of the lesser trochanter fragment at three months postoperatively. Results: The bone union of the lesser trochanter fragment was achieved in 24 cases (92%) in group B and 30 cases (64%) in group N. Compared with group N, group B showed a significantly increased number of mild and moderate deformities but decreased number of severe deformity and nonunion (P < 0.001). Postoperative complications were not observed in both groups. Conclusions: From the viewpoint of increasing lesser trochanteric bone union ratio, fixation of the lesser trochanter fragment using nonabsorbable tape in the treatment of trochanteric fractures could be an effective procedure.

Purpose: Medial meniscus ramp lesions (MMRLs), lateral meniscus posterior root tears (LMPRTs), and anterolateral complex injuries (ALCIs) are major secondary stabiliser injuries associated with anterior cruciate ligament (ACL) injuries. This study aimed to investigate the effect of the number of secondary stabiliser injuries on knee instability in ACL injuries., Methods: Patients who underwent primary ACL reconstruction between January 2017 and May 2023 were enroled in this study. Exclusion criteria encompassed patients with other ligament injuries, a history of contralateral knee injury, hyperextension, flexion contracture and meniscus injuries other than MMRL or LMPRT. Ultimately, 158 patients (mean age: 25.3 years; 81 males and 77 females) were included in this study, and the presence of MMRL, LMPRT and ALCI was investigated. Patients were categorised into four groups based on the number of ACL and secondary stabiliser injuries: single (isolated ACL injury), dual, triad and tetrad. Subsequently, the groups were compared regarding pivot shift grade, quantitative rotational instability measured using an inertial sensor, and anterior tibial translation (ATT)., Results: Secondary stabiliser injuries identified included ALCI 85 (53.8%), MMRL 58 (36.7%) and LMPRT 23 (14.6%). The distribution of patients in the single, dual, triad and tetrad groups was 45 (28.5%), 68 (43.0%), 37 (23.4%) and 8 (5.1%), respectively. High-grade pivot shifts were observed in 33.3% (15 out of 45) of the single group, 63.2% (43 out of 68) of the dual group, 67.6% (25 out of 37) of the triad group, and 100% (8 out of 8) of the tetrad group. Quantitative evaluations using the inertial sensor revealed significantly lower acceleration in the isolated ACL injury group compared to the other groups (p < 0.05). No significant difference was observed in ATT measurements (n.s.)., Conclusion: The combination of secondary stabiliser injuries led to higher instability. Therefore, it is important to carefully diagnose these injuries and devise appropriate treatment plans, particularly in cases of high knee instability., Level of Evidence: Level III diagnostic., (© 2025 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Energy conversion efficiency of human gait can be evaluated by calculating the ratio of conversion of mechanical energy from vertical motion to horizontal motion of the center of gravity through the movement of the joints. Osteoarthritis (OA) of the knee joint impairs this energy conversion efficiency. Total knee arthroplasty is the standard treatment for knee OA. However, its effect on energy conversion efficiency is unclear. In this study, we investigated how energy conversion efficiency changed in the gait of patients with knee OA before and after surgery., Methods: Twelve patients with unilateral knee OA who underwent total knee arthroplasty were included. Ground walking was measured using a motion capture system (VICON®) before and 6 months after surgery. We calculated potential and kinetic energy from the coordinate change of the center of mass to obtain energy conversion efficiency. Other gait parameters such as gait speed, vertical movement distance of the body center, step length, hip joint angle, and trailing and leading limb angles were assessed., Results: Energy conversion efficiency on the operated side significantly improved from 41.4 ± 12.2% to 57.5 ± 9.2% 6 months after surgery. Other gait parameters on the operated side were significantly improved after surgery compared with before surgery. Step length on the operated and the non-operated sides and trailing limb angles on the non-operated side before surgery correlated to energy conversion efficiency, while at 6 months after surgery, gait speed and step length on the non-operated side correlated to energy conversion efficiency., Conclusion: Energy conversion efficiency was strongly improved postoperatively in patients with knee OA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Capsule repair plays an important role in total joint arthroplasty. However, no biomechanical studies have indicated the optimal suturing methods and materials in capsule repair. This study aimed to evaluate the effectiveness of the suturing methods (interrupted and continuous sutures) and materials (Vicryl and Stratafix) for capsule repair using porcine skin specimens., Methods: Three groups with eight porcine skin specimens were used as a surrogate for human capsules. The V-I group with 1-Vicryl interrupted sutures, V-C group with 1-Vicryl continuous sutures, and S group with 1-Stratafix continuous sutures were analyzed by tensile test to investigate the maximum failure load. Eight pieces of 1-Viclyl and nine pieces of 1-Stratafix were used to analyze the suture material's strength. Corrected maximum failure load was calculated by taking the ratio of the mean maximum tensile strengths of Vicryl and Stratafix sutures., Findings: The maximum failure loads were 275.52 ± 62.45 N, 465.81 ± 57.91 N, and 303.08 ± 37.16 N in V-I, V-C, and S groups, respectively. Regarding the suture material's strength, 1-Vicryl showed significantly higher maximum failure load than 1-Stratafix (47.37 ± 4.58 N vs 35.62 ± 4.35 N). When normalizing the influence of different suture materials on tensile strength, the corrected maximum failure load was 207.17 ± 46.96 N in V-I group and 350.27 ± 43.55 N in V-C group., Interpretation: Our findings showed that Stratafix, barbed continuous suture, could be an alternative option to conventional Vicryl suture for capsule repair., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We aimed to compare the clinical and surgical outcomes of cemented vs uncemented bipolar hemiarthroplasty in the treatment of femoral neck fractures in the elderly. Patients (n = 99) without preoperative cardiopulmonary problems undergoing bipolar hemiarthroplasty for femoral neck fracture between August 2015 and February 2019 were randomly divided into cemented (group C) and uncemented (group U) stem fixation groups. Mean operative time, mean intraoperative blood loss, and percentage of intraoperative use of vasopressors, pre- and postoperative activities of daily living (ADL), incidence of postoperative complications, and radiological evaluation of stem alignment were evaluated. A total of 99 patients were included (group C, n = 42; group U, n = 57). Group C had a significantly longer mean operative time (P < .001) and a significantly higher percentage of intraoperative vasopressor use as compared to group U (P < .05). In contrast, the amount of intraoperative blood loss was similar between the 2 groups (P = .30). Likewise, there was no statistically significant difference in pre- and postoperative ADL performance between the groups (P = .70 and .44, respectively). Postoperative computed tomography revealed that stem anteversion was higher in group C than in group U (P < .05). Cemented and uncemented stems were equivalent in terms of blood loss and postoperative complications in patients with femoral neck fractures. Uncemented stem showed advantages in reducing operative time and intraoperative vasopressor administration. Also, fixation method was not investigated in this study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

In most previous studies investigating return to preinjury level of sport (RTPS) after anterior cruciate ligament reconstruction (ACLR), whether patients continue aiming for RTPS not only before but also after ACLR was unclear because environmental and social factors were not considered. Herein, we aimed to evaluate factors associated with RTPS among athletes who desired to achieve RTPS even after ACLR, excluding patients who no longer desire this goal owing to environmental and social factors. Ninety-two patients who underwent primary double-bundle ACLR with a minimum 2-year follow-up and desired to achieve RTPS before surgery were retrospectively enrolled. Twelve (13%) patients who no longer desired to achieve RTPS after ACLR owing to environmental and social factors were excluded. Sixty-nine patients were included in the final cohort. At the final follow-up, the patients were split into two groups: those who achieved (R group) or did not achieve (N group) RTPS based on patient self-assessment. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm scores were also determined. The anterior tibial translation in the Lachman test and acceleration and external rotational angular velocity (ERAV) in the pivot shift test were measured at the hardware removal operation. Significant differences were observed for preinjury level of sports between the groups ( p  < 0.05). The rate of RTPS in competitive athletes was lower than that in recreational athletes (20/46: 43% vs. 16/22: 73%; p =.037). Lysholm score, KOOS symptom, pain, and quality of life showed higher values in the R group than in the N group ( p  < 0.050). Acceleration was significantly lower in the R group than in the N group ( p  = 0.028). Competitive level of sports is a risk factor for failure to achieve RTPS. The postoperative functional outcomes in the group that achieved RTPS showed more favorable results. These results provide important information to enable the surgeons to consider the appropriate surgical plan for competitive athletes who desire to achieve RTPS after ACLR., Competing Interests: None declared., (Thieme. All rights reserved.)

Gallein is a known Gβγ subunit inhibitor, but its function in bone metabolism, especially in osteoblasts, and its molecular mechanism remains to be elucidated. Osteoprotegerin (OPG), which is secreted from osteoblasts, binds to nuclear factor kB receptor activator (RANK) ligand (RANKL) as a decoy receptor, prevents RANKL-RANK binding, and inhibits bone resorption. IL-6 is not only a bone resorption factor but also as a bone metabolism regulator. Prostaglandin F2α (PGF2α) promotes p44/p42 MAPK, p38 MAPK and stress-activated protein kinase/JNK phosphorylation in osteoblast-like MC3T3-E1 cells. In MC3T3-E1 cells, activated p44/p42 and p38 MAPKs promote IL-6 secretion and activated p44/p42 and p38 MAPKs and JNK promote OPG secretion. The present study aimed to investigate the effect and mechanism of gallein on PGF2α-induced OPG and IL-6 secretion using an osteoblastic MC3T3-E1 cell line. It was found that gallein significantly increased PGF2α-induced OPG and IL-6 secretion in the MC3T3-E1 cell. By contrast, fluorescein, which is a gallein-like compound that does not bind to Gβγ, did not affect PGF2α-induced OPG and IL-6 secretion. Gallein significantly improved the PGF2α-induced OPG and IL-6 mRNA expression levels. Gallein did not affect the PGF2α-activated phosphorylation of p44/p42 and p38 MAPKs and JNK. Gallein increased PGF2α-induced OPG and IL-6 secretion in osteoblasts, indicating that gallein may regulate bone remodeling via OPG/IL-6 in bone metabolism., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Gallein is known as an inhibitor of Gβγ subunits, but roles of gallein in bone metabolism have not been reported. Fibroblast growth factor 2 (FGF-2) increases angiogenesis and promotes bone regeneration during the early stages of fracture healing. Osteoprotegerin (OPG) secreted by osteoblasts, binds to the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) as a decoy receptor and prevents RANKL from binding to RANK, resulting in the suppression of bone resorption. Our previous report demonstrated that FGF-2 activates the phosphorylation of p38 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (JNK), and p44/p42 MAPK in osteoblast-like MC3T3-E1 cells. Additionally, FGF-2-activated phosphorylation of p38 MAPK and JNK but not p44/p42 MAPK is positively involved in OPG synthesis in these cells. This work aimed to investigate the effects of gallein on the FGF-2-elicited OPG synthesis in osteoblast-like MC3T3-E1 cells and the mechanism. Our findings demonstrated that gallein significantly increased the FGF-2-elicited OPG synthesis in MC3T3-E1 cells. By contrast, fluorescein, gallein-like compound that does not bind Gβγ, did not affect the FGF-2-elicited OPG synthesis. Gallein significantly enhanced the FGF-2-induced OPG mRNA expression levels. Gallein did not affect the FGF-2-activated phosphorylation of p38 MAPK and p44/p42 MAPK, but significantly increased the FGF-2-activated phosphorylation of JNK, while fluorescein did not affect JNK phosphorylation. SP600125, a specific JNK inhibitor, strongly inhibited gallein-induced enhancement of FGF-2-induced OPG synthesis and mRNA expression levels. Our results indicated that gallein increases the FGF-2-induced OPG synthesis due to the JNK activation in the osteoblast., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate the effects of ramp lesion (RL) and its repair on knee instability in patients with anterior cruciate ligament (ACL) injury by quantitatively assessing anteroposterior and rotational knee instability before and after ACL reconstruction., Methods: All primary double-bundle ACL reconstructions using hamstring autografts between 2016 and 2021 were evaluated retrospectively. Patients with RLs without other meniscal injuries were included in group R, whereas those with isolated ACL injuries constituted group C. RL was repaired using all-inside devices in all patients in group R. Knee instability, including the amount of anterior tibial translation (ATT), and the acceleration and external rotational angular velocity of the knee joint (ERAV) during the pivot-shift test were assessed at the time of surgery. The pivot-shift test grade was recorded., Results: A total of 73 patients were included in this study. Preoperatively, group R (n = 23) had significantly greater pivot-shift grades (P = .039), ATT (6.0 mm, group R; 4.5 mm, group C, P < .001), acceleration (6.8, 2.8; P = .037), and ERAV (3.9, 2.8; P = .001) than group C (n = 50). Intraoperatively, ATT (-1.0 mm, -1.0 mm; P < .001), acceleration (1.2, 1.1; P < .001), and ERAV (1.4, 1.2; P < .001) were significantly decreased compared with the preoperative values in both groups. No significant differences in these values were observed between groups R and C., Conclusions: ACL-injured knees accompanied by RLs exhibited significantly greater anteroposterior and rotatory instability than knees with isolated ACL injuries; increased knee instability can be effectively addressed by performing RL repair in conjunction with ACL reconstruction. The quantitative assessments employed-specifically measuring ATT, acceleration, and ERAV during the pivot-shift test-have allowed us to delineate these aspects of knee instability with greater precision., Level of Evidence: Level Ⅲ, retrospective comparative study., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and d-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD 2 , is expressed on osteoblasts. We previously reported that prostaglandin D 2 (PGD 2 ) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD 2 in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD 2 in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD 2 . Not fluorescein but gallein amplified the PGD 2 -stimulated releases of OPG and IL-6. Gallein enhanced the PGD 2 -upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD 2 -induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD 2 -stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation., Competing Interests: Declaration of competing interest The authors have declared that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Postoperative residual rotatory laxity remains despite improvement in surgical techniques for anterior cruciate ligament (ACL) reconstruction (ACLR)., Purpose: To evaluate factors associated with residual pivot shift after ACLR by quantitative measurement of the pivot shift before and after surgery., Study Design: Case-control study; Level of evidence, 3., Methods: A total of 97 patients who underwent primary double-bundle ACLR between June 2016 and March 2021 and underwent surgery to remove staples, with at least 12 months of follow-up evaluation, were enrolled. Quantitative measurements were performed under general anesthesia immediately before ACLR (preoperatively), after temporary fixation of the ACL graft (intraoperatively), and immediately before staple removal (postoperatively). The laxity of pivot shift was assessed using inertial sensors to measure acceleration and external rotational angular velocity (ERAV). Descriptive data were assessed for associations with postoperative acceleration and ERAV in a univariate analysis. A multiple linear regression analysis was performed to identify factors associated with postoperative acceleration and ERAV., Results: Anterior tibial translation, acceleration, and ERAV increased from intra- to postoperatively ( P < .05). Factors significantly associated with postoperative acceleration were age (β = -0.238; P = .021), lateral posterior tibial slope (PTS) (β = 0.194; P = .048), and preoperative acceleration (β = 0.261; P = .008). Factors significantly affecting postoperative ERAV were age (β = -0.222; P = .029), ramp lesions (β = 0.212; P = .027), and preoperative ERAV (β = 0.323; P = .001)., Conclusion: Greater preoperative laxity in the pivot shift was the factor having the most significant association with residual pivot shift after ACLR using quantitative measurements under general anesthesia. Younger age, higher lateral PTS, and concomitant ramp lesions were significant predictors of residual pivot shift. These findings can help pre- and intraoperative decision-making regarding whether an anterolateral structure augmentation should be added., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background: An unstable trochanteric femoral fracture is a serious injury, with a 1-year mortality rate of 5.4% to 24.9%, for which there is currently no standard treatment method. The lag screw insertion site is one of the primary contact areas between the cortical bone and an intramedullary nail. We hypothesized that a posterolateral fracture causes intramedullary nail instability when the posterolateral fracture line interferes with lag screw insertion. The purpose of the present study was to investigate the effect of posterolateral fracture line morphology on intramedullary nail stability by simulating unstable trochanteric femoral fractures with a posterolateral fracture fragment., Methods: Eighteen custom-made synthetic osteoporotic bone samples were used in the present study. Nine samples had a posterolateral fracture line interfering with the lag screw insertion hole (Fracture A), and the other 9 had a fracture line 10 mm away from the hole (Fracture B). Cyclic loading (750 N) was applied to the femoral head 1,500 times. Movement of the end cap attached to the intramedullary nail was recorded. The amplitudes of motion in the coronal plane (coronal swing motion), sagittal plane (sagittal swing motion), and axial plane (total swing motion) were evaluated. The change in the neck-shaft angle was evaluated on photographs that were made before and after the test. Medial cortical displacement was measured before and after the test., Results: Two Fracture-A samples were excluded because the amplitude of sagittal swing motion was too large. The mean values for coronal, sagittal, and total swing motion were 1.13 ± 0.28 mm and 0.51 ± 0.09 mm (p < 0.001), 0.50 ± 0.12 mm and 0.46 ± 0.09 mm (p = 0.46), and 1.24 ± 0.24 mm and 0.69 ± 0.11 mm (p < 0.001) for Fractures A and B, respectively. The mean neck-shaft angle change was -8.29° ± 2.69° and -3.56° ± 2.35° for Fractures A and B, respectively (p = 0.002). The mean displacement of the medial cortex was 0.38 ± 1.12 mm and 0.12 ± 0.37 mm for Fractures A and B, respectively (p = 0.57)., Conclusions: This study showed that an unstable trochanteric femoral fracture with a posterolateral fracture line that interferes with the lag screw insertion holes is a risk factor for increased intramedullary nail instability., Competing Interests: Disclosure: This study was funded by Teijin Nakashima Medical Co., Ltd. (the manufacturer of the intramedullary nails used in the study), and also partly supported by a Grant-in-Aid for Scientific Research (19K18471) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and a Grant-in-Aid for Research (2213035) from Nagoya City University. The Article Processing Charge for open access publication was funded by Teijin Nakashima Medical Co., Ltd. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A601)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Purpose: The aim of this study is to assess the dynamics of the tear site of meniscal ramp lesions, particularly considering knee flexion angles, and validate anchor fixation using an all-inside device., Methods: Eight Thiel-embalmed paired cadaveric knees with their whole bodies were used in this study. The ramp lesions were created arthroscopically, and ramp lesion dynamics were evaluated by gradually extending the knee from 90° of knee flexion. Changes in the gap and step-off (0: no step-off; 1: cross-sectional overlap exists; and 2: tibial articular surface exposed) were evaluated at 90°, 60°, 30°, and 10° of knee flexion. After dynamic evaluation, all-inside repairs of the ramp lesions using all-inside devices were conducted. Dissection was performed to confirm the position of anchor fixation., Results: As the knee was extended, the gap significantly decreased at all knee flexion angles. Similarly, the step-off grade decreased as the knee was extended, and the step-off completely disappeared in all cases when the knee was extended from 30° to 10°. The average knee flexion angle at which the gap and step-off completely disappeared was 22.5°. After suturing the ramp lesion, arthroscopic evaluation showed that the gap had disappeared and the step-off had been repaired in all cases. Anchor fixation locations were not found within the joint but were fixed to the semimembranosus tendon or its surrounding articular capsule. Overall, 31% (5/16) anchors were fixed to the attachment site of the semimembranosus tendon, whereas the remaining were fixed to the articular capsule, located peripherally to the semimembranosus tendon., Conclusion: Suturing with an all-inside device for ramp lesions is a good option, and the repair in knee extension was found to be reasonable, considering the dynamics of ramp lesions in this study., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: Proximal humeral fractures cause large intramedullary bone defects after humeral-head reduction. Hydroxyapatite/poly-L-lactide (HA/PLLA) materials are widely used for various fractures. However, the efficacy of endosteal strut using a HA/PLLA mesh tube (ES-HA/PLLA) with a locking plate for treating proximal humeral fractures was not reported. The purpose of this study is to examine the efficacy of ES-HA/PLLA with a proximal humeral locking plate in proximal humeral fractures., Methods: Seventeen patients with proximal humeral fractures treated using ES-HA/PLLA with a locking plate from November 2017 to November 2021 were evaluated. The range of motion of the shoulder and postoperative complications were assessed at the final follow-up. Radiographs were evaluated to assess bone union and loss of reduction by measuring humeral-head height (HHH) and humeral neck-shaft angle (NSA)., Results: The average flexion and external rotation of the shoulder at the final follow-up were 137° (range, 90-180°) and 39° (range, - 10 to 60°), respectively. All fractures were united. The average HHH and NSA just after the surgery and final follow-up were 12.5 mm and 11.6 mm and 129.9° and 127.4°, respectively. Two patients presented screw perforation of the humeral head. One patient underwent implant removal due to infection. Avascular necrosis of the humeral head was observed in one patient with arthritis mutilans., Conclusions: The use of ES-HA/PLLA with a proximal humeral locking plate resulted in bone union in all patients and prevented postoperative loss of reduction. ES-HA/PLLA is one of the treatment options for proximal humeral fractures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Heat shock protein 70 (HSP70) functions as an ATP‑dependent molecular chaperone under stress and is involved in protein homeostasis, folding and degradation. HSP70 inhibitors amplify TGF‑β‑stimulated VEGF synthesis in the mouse osteoblastic MC3T3‑E1 cell line. Basic fibroblast growth factor (bFGF) stimulates IL‑6 release via p38 MAPK in MC3T3‑E1 osteoblast‑like cells. In the present study, the effects of HSP70 on the bFGF‑stimulated release of IL‑6 was evaluated using MC3T3‑E1 osteoblast‑like cells. IL‑6 release and mRNA expression levels were analyzed using ELISA and reverse transcription‑quantitative PCR, respectively. Phosphorylation of p38 MAPK and HSP70 was assessed using western blotting. HSP70 inhibitor VER‑155008 significantly increased the bFGF‑stimulated release of IL‑6 in both MC3T3‑E1 osteoblastic cells and normal human osteoblasts. Furthermore, VER‑155008 significantly enhanced the mRNA expression levels of IL‑6 stimulated by bFGF. Western blotting demonstrated a significant increase in the bFGF‑stimulated phosphorylation of p38 MAPK in VER‑155008‑treated MC3T3‑E1 cells. A significant increase in the bFGF‑stimulated phosphorylation of p38 MAPK was also demonstrated in MC3T3‑E1 cells treated with YM‑08, another HSP70 inhibitor. VER‑155008 or YM‑08 did not significantly affect the expression of HSP70 with or without bFGF stimulation. Finally, the specific p38 MAPK inhibitor SB203580 markedly suppressed the enhancing effects of VER‑155008 on bFGF‑stimulated release of IL‑6. Taken together, these results indicated that HSP70 inhibitor amplified bFGF‑stimulated release of IL‑6 through p38 MAPK activation in the osteoblastic MC3T3‑E1 cell line.

Resveratrol is a natural polyphenol found in grapes and beneficial for human health. Resveratrol regulates basic fibroblast growth factor (bFGF)-induced osteoprotegerin synthesis through Akt pathway in osteoblast-like MC3T3-E1 cells. In this study, we investigated resveratrol effects on bFGF-induced macrophage colony-stimulating factor (M-CSF) synthesis in MC3T3-E1 cells. bFGF significantly stimulated release and mRNA expression of M-CSF, which was reduced by resveratrol and SRT1720, sirtuin 1 (SIRT1) activator. Inauhzin, SIRT1 inhibitor, reversed inhibitory effects of resveratrol on bFGF-induced mRNA expression of M-CSF. Deguelin, Akt inhibitor, and LY294002, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced bFGF-induced M-CSF synthesis. Inauhzin reversed inhibitory effects of resveratrol on bFGF-induced Akt phosphorylation. Suppressive effect of resveratrol on bFGF-induced osteoprotegerin mRNA expression was confirmed in the identical samples using in experiment of M-CSF mRNA expression. Therefore, resveratrol reduces bFGF-induced M-CSF synthesis in addition to osteoprotegerin synthesis by inhibiting PI3-kinase/Akt pathway and suppressive effects are mediated through SIRT1 activation in osteoblasts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Patients with Parkinson's disease have a high dislocation rate after total hip arthroplasty (THA). This study describes a case with severe Parkinson's disease who developed rapidly destructive coxarthrosis (RDC) and underwent THA using a dual mobility cup after a levodopa-carbidopa intestinal gel (LCIG) infusion., Case Presentation: The patient is a 59-year-old female with a ten-year history of Parkinson's disease, which was first treated with oral levodopa. The patient developed RDC of the right hip joint. However, THA was difficult owing to Parkinson's disease and its treatment side effects, such as wearing-off, dyskinesia, and freezing of the gait, Thus, LCIG was initiated, and improvement in wearing-off and dyskinesia was observed. Two months after the LCIG therapy, the disease was controlled well. THA was subsequently performed using a dual mobility cup to prevent postoperative dislocation. Postoperatively, LCIG therapy was continuously administered to carefully manage the disease, which was controlled well with no increase in wearing-off and dyskinesia after surgery. At 1 year after surgery, the walking speed, stride length, and the Harris hip score improved compared to preoperatively. The UPDRS III motor score improved to eight without signs of wearing-off or dyskinesia. The Hoehn-Yahr scale was II in the "on" period and remained unchanged 1 year after surgery. The patient could walk without a cane and had satisfactory functional outcomes., Conclusion: This case proved that LCIG treatment performed preoperatively, followed by THA using a dual mobility cup, and strict management of Parkinson's disease could result in a satisfactory clinical course without recurrence of wearing-off and dyskinesia. Similar procedures may benefit other patients with Parkinson's disease who have previously been deemed unsuitable for THA., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

We describe the wiring technique and evaluate the radiographic and clinical outcomes of treatment with a pin and wire system (PWS) for comminuted patella fractures. From June 2013 to October 2018, 33 patients with comminuted patella fractures were treated using a PWS. Open reduction and internal fixation was performed with multiple pins and a wire. All patients were allowed full weight bearing without a brace. Radiographs were obtained to evaluate bone union, implant breakage, back-out of pins, and intra-articular gaps and step-off. Clinical outcomes and postoperative complications were assessed at final follow-up examination. All fractures were united. Thirteen cable wires in 13 patients were partially broken without displacement of fracture at an average of 7.4 months (range, 1-19 months) postoperatively. The average preoperative, postoperative, and final follow-up intra-articular gap and step-off were 11.7 mm, 0.5 mm, and 0.03 mm and 6.6 mm, 0.4 mm, and 0.2 mm, respectively. The average postoperative pin displacement was 0.1 mm (range, 0-0.8 mm). Deep infection was not observed after the surgery. The implant removal rate was 21% (7 of 33). Among these, the symptomatic implant removal rate was 9% (3 of 33). Additionally, 3 of 7 patients with implant removal had broken wires. The average flexion and extension of knee joints were 139.7° (range, 120°-150°) and -0.9° (range, -10° to 0°), respectively. A PWS prevents back-out of the pins and reduces intra-articular gaps and step-off distances to acceptable levels, even if the cable wire is partially broken. Therefore, a PWS is a good treatment option for comminuted patella fractures. [ Orthopedics . 2023;46(5):291-296.].

Objective: Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL-6) is significantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL-6. Adolescent JIO is particularly challenging to treat and has poor outcome. This study determined if IL-6 receptor blockade prevents bone loss and improves the bone healing in adolescent JIO., Method: Adolescent mice (12-week-old) surgically induced with JIO were treated with either saline or MR16-1, an IL-6 receptor blocker., Results: Micro-CT assessment showed significantly increased bone volume ( p  ​< ​0.001, Cohen's d  ​= ​2.0) and trabecular bone thickness ( p  ​< ​0.001, d  ​= ​2.3) after the MR16-1 treatment. Histomorphometric assessment showed significantly increased osteoblast number ( p  ​< ​0.01, d  ​= ​2.3), bone formation rate ( p  ​< ​0.01, d  ​= ​4.3), and mineral apposition rate ( p  ​< ​0.01, d  ​= ​4.1) after the MR16-1 treatment. The number of osteoclasts was unchanged. Histologic assessment showed significantly increased revascularization ( p  ​< ​0.01) and restoration of the necrotic marrow with new hematopoietic bone marrow ( p  ​< ​0.01). Vascular endothelial growth factor (VEGF) expression was increased in the revascularized area and the articular cartilage, and in the cultured chondrocytes treated with IL-6 receptor inhibitor., Conclusion: IL-6 blockade in adolescent mice with JIO enhanced bone formation and revascularization. The findings suggest IL-6 receptor blocker as a potential medical therapy for adolescent JIO., Competing Interests: The author (H.K.) has received tocilizumab from Genentech Inc. for an unrelated research work. All other authors have no conflicts of interest (COI). Study data will be available upon request without COI., (© 2023 The Author(s).)

Oncostatin M produced by osteal macrophages plays a significant role in fracture healing. Osteoprotegerin (OPG) secreted by osteoblasts, binds to the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) as a decoy receptor and prevents RANKL from binding to RANK, resulting in bone resorption suppression. Interleukin-6 (IL-6) is a pro-inflammatory cytokine and generally regulates bone resorption. However, accumulating evidence suggests that IL-6 plays pivotal roles in bone formation. We previously showed that prostaglandin D 2 (PGD 2 ) induces OPG synthesis by activating p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. Furthermore, we demonstrated that PGD 2 stimulates IL-6 synthesis by activating p38 MAP kinase and p44/p42 MAP kinase in MC3T3-E1 cells. In the present study, we investigated whether oncostatin M affects PGD 2 -stimulated OPG and IL-6 synthesis in MC3T3-E1 cells through MAP kinase activation. The osteoblast-like MC3T3-E1 cells and normal human osteoblasts were treated with oncostatin M and subsequently stimulated with PGD 2 . Consequently, oncostatin M significantly increased the PGD 2 -stimulated OPG and IL-6 release in both cells. Oncostatin M significantly enhanced mRNA expression levels of OPG and IL-6 induced by PGD 2 similarly in both cells. Regarding the signaling mechanism, oncostatin M did not affect the phosphorylation of p38 MAP kinase, SAPK/JNK, and p44/p42 MAP kinase. Our results suggest that oncostatin M upregulates the PGD 2 -stimulated OPG and IL-6 synthesis in osteoblasts and therefore affects bone remodeling. However, OPG and IL-6 synthesis are not mediated through p38 MAP kinase, p44/p42 MAP kinase, or SAPK/JNK pathways., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hydroxyapatite (HA) augments are used to treat trochanteric femoral fractures. However, the efficacy of HA augmentation has not been fully described in trochanteric femoral fracture surgery. In total, 85 patients were enrolled in the present study; all had trochanteric femoral fractures between January 2016 and October 2020, 45 with HA (HA group) and 40 without HA (N group). The intraoperative lag screw insertion torque was directly measured and the amount of lag screw telescoping with and without HA augmentation after surgery was analyzed. Maximum lag screw insertion torque (max-torque), bone mineral density in the opposite femoral neck (n-BMD), tip apex distance (TAD) of the lag screw, radiographic findings including fracture union, the amounts of lag screw telescoping and occurrence of complications were evaluated. A total of 12 patients were excluded if they were aged under 60 years old, had ipsilateral surgery and disorders in the hip joint, TAD of the lag screw ≥26 mm on postoperative radiographs and had measurement errors. A total of 73 fractures could be analyzed: HA group (n=36) and N group (n=37). Max-torque/n-BMD ratios were higher in the HA group compared with in the N group (7.23±2.71 vs. 5.93±1.91 g/cm 2 ·N·m; P=0.04). The amounts of lag screw telescoping in the HA group were smaller compared with the N group (1.41±2.00 vs. 2.58±2.34; P=0.05). Evaluation of screw insertion torque showed maximum screw insertion torque correlated well with n-BMD in both groups, HA (R=0.57; P<0.01) and N group (R=0.64; P<0.01). No correlation was found between maximum screw insertion torque and TAD in both groups, HA (R=-0.10; P=0.62) and N group (R=0.02; P=0.93). All fractures were radiographically united without any complications. These results support the effectiveness of HA augmentation, indicating higher resistance against rotational instability and reduced lag screw telescoping in trochanteric femoral fracture treatment., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Concomitant anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction has been reported as an effective technique for providing rotational control of the knee. However, the intraoperative risk of collision with an ACL tunnel during the drilling for the femoral ALL tunnel has been described. The purpose of this study was to investigate the various femoral drilling procedures to avoid tunnel collisions during combined double-bundle ACL and ALL reconstruction. Nine cadaveric knees were used in this study. ACL drilling was performed through the anteromedial portal to footprints of the posterolateral bundle at 120° (PL120) and 135° (PL135) knee flexion and the anteromedial bundle at 120° (AM120) and 135° (AM135) knee flexion. ALL drilling was performed at 0° (Cor0-ALL) and 30° (Cor30-ALL) coronal angles using a Kirschner wire (K-wire). The distance between the ALL footprint and ACL K-wire outlets, axial angles of ALL K-wires colliding with ACL K-wires, and distances from the ALL footprint to the collision point were measured. From these values, the safe zone, defined as the range of axial angles in which no collisions or penetrations occurred, was identified by simulation of tunnels utilized for reconstruction grafts in each drilling procedure. The point-to-point distance from the ALL footprint to the K-wire outlet was significantly greater in the AM120 than the AM135 (13.5 ± 3.1, 10.8 ± 3.2 mm; p  = 0.048) and in the PL135 than the PL120 (18.3 ± 5.5, 16.1 ± 6.5 mm; p  = 0.005) conditions, respectively. During an ACL drilling combination of PL135/AM120, a safe zone of > 45° in Cor30-ALL was identified. With a narrow safe zone during the PL135/AM120 combination only, the risk of femoral tunnel collisions in combined double-bundle ACL and ALL reconstruction is high. AM drilling at 120° and PL drilling at > 135° knee flexion, combined with ALL drilling at 30° coronal angle and > 45° axial angle, may reduce this risk., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Oncostatin M produced by osteal macrophages, a cytokine that belongs to the interleukin-6 family, is implicated in bone fracture healing. Macrophage colony-stimulating factor (M-CSF) secreted from osteoblasts plays an important role in osteoclastogenesis. We have previously reported that tumor necrosis factor-α (TNF-α), a potent bone resorptive agent, stimulates the activation of p44/p42 mitogen-activated protein (MAP) kinase, Akt, and p70 S6 kinase in osteoblast-like MC3T3-E1 cells, and induces the synthesis of M-CSF at least in part via Akt., Objective: In the present study, we investigated whether oncostatin M affects the TNF-α-induced M-CSF synthesis in MC3T3-E1 cells and the underlying mechanisms., Methods: Clonal osteoblast-like MC3T3-E1 cells were treated with oncostatin M or rapamycin and then stimulated with TNF-α. M-CSF release was assessed by ELISA. M-CSF mRNA expression level was assessed by real-time RT-PCR. Phosphorylation of Akt, p44/p42 MAP kinase, and p70 S6 kinase was detected by Western blot analysis., Results: Oncostatin M dose-dependently reduced the TNF-α-stimulated M-CSF release. The expression of M-CSF mRNA induced by TNF-α was significantly suppressed by oncostatin M. Rapamycin, an inhibitor of mTOR/p70 S6 kinase, had little effect on the M-CSF release by TNF-α. Oncostatin M significantly reduced the TNF-α-induced phosphorylation of Akt and p44/p42 MAP kinase. However, the p70 S6 kinase phosphorylation by TNF-α was not affected by oncostatin M., Conclusion: These results strongly suggest that oncostatin M attenuates TNF-α-stimulated synthesis of M-CSF in osteoblasts, and the inhibitory effect is exerted at a point upstream of Akt and p44/p42 MAP kinase but not p70 S6 kinase.

Background: Forged unsintered hydroxyapatite and poly l-lactic acid ( F-u-HA/PLLA) screw is bioactivite, bioabsorbable, and radiopaque with high mechanical strength. Its efficacy has been previously demonstrated in the treatment of lateral humeral condylar, lateral tibial condylar, ankle, and patellar fractures. However, studies on its efficacy in treatment of calcaneal fractures is lacking. This study aimed to compare the postoperative results of F-u-HA/PLLA screw fixation and locking plate fixation for intra-articular calcaneal fractures., Methods: From January 2013 to December 2019, 47 closed intra-articular fractures treated with either F-u-HA/PLLA screws (group S, 18 feet in 17 patients) or locking plates (group P, 29 feet in 28 patients) in a single trauma center were retrospectively reviewed. The sinus tarsi approach was used in both groups. The time to bone union, step-off, varus deformity, Bohler's angle, and width and height of the calcaneus were assessed after surgery. Ankle joint range of motion (ROM) and postoperative complications were also assessed., Results: All fractures were successfully treated. The Kaplan-Meier curves of the two groups showed similar trends. The log-rank test showed no significant difference in the time to bone union between the two groups (p = 0.48). In the Cox proportional hazards model adjusted for preoperative width and Bohler's angle, the hazard ratio for bone union was not statistically significant (HR: 1.13, 95%CI: 0.50-2.56, p = 0.78). Other variables included step-off (group S: 2.0 vs group P: 2.2 mm, p = 0.84), varus deformity (2.0° vs. 3.0°, p = 0.7), Gissane's angle (103.5° vs 104.0°, p = 0.84), width (38.0 vs 34.8 mm, p = 0.12), height (42.1 vs 44.0 mm, p = 0.07), and ankle ROM degrees (dorsal flexion, 20.0° vs. 20.0°, p = 0.13; plantar flexion 40.0° vs 40.0°, p = 0.56), which were not significantly different between groups P and S. The Bohler's angle was smaller in group S than in group P (20.5° vs 27.0°, p < 0.01). No skin necrosis or infection was observed in either group., Conclusion: Postoperative results of F-u-HA/PLLA screw fixation using the sinus tarsi approach for intra-articular calcaneal fractures were as good as those of locking plate fixation., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Published by Elsevier Ltd.)

The Revelation Hip System is a cementless stem with a lateral flare concept. Stable fixation is achieved by fitting the stem to the medullary cavity of the proximal lateral femoral cortex. Patients who have undergone total hip arthroplasty using the Revelation Hip System show good postoperative clinical and radiographic outcomes. However, to the best of our knowledge, no study has reported the relationship between stem fitting and clinical or radiological outcomes after the surgery. In the present study, we investigated the relationship between stem fitting and clinical or radiological outcomes after total hip arthroplasty (THA) using the Revelation Hip System. In this study, 28 hips of 26 patients who were treated with the Revelation Hip System for osteoarthritis, osteonecrosis of the femoral head, rheumatoid arthritis, and rapidly destructive coxarthropathy and were followed up for > 5 y were enrolled. These patients were divided into two groups, including the rest fit group (11 hips, group R) and the control group (17 hips, group C), according to the results of the density mapping analysis. In group R, the lateral side of the stem fits on the medullary cavity of the proximal lateral femoral cortex, while in group C, the lateral side of the stem did not fit. Radiographic results showed no significant differences between the groups in terms of stem alignment, subsidence, and stress shielding around the cup. The incidence of stress shielding around the stem in zone 7 was not significant but tended to be higher in group R than in group C (p = 0.052). Clinical outcomes showed no significant differences between group R and group C in terms of the Harris hip score, the Japanese Orthopaedic Association (JOA) score, and the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ) total score. However, pain complaints that were assessed by patient-reported outcomes using the 36-Item Short Form Health Survey (SF-36) bodily pain and vitality subscales and the JHEQ pain subscale were significantly higher in group R than in group C at the final follow-up. These results suggest that some patients had pain complaint even if the stems were inserted as per the concept after THA with the Revelation Hip System.Trial Registration911., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E1 (PGE1) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE1-stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation. The osteoblast-like MC3T3-E1 cells were treated with HSP70 inhibitors-VER-155008 and YM-08-, PD98059, SB203580 or SP600125 and then stimulated with PGE1. IL-6 synthesis was evaluated using an IL-6 enzyme-linked immunosorbent assay kit. IL-6 mRNA expression was measured by real-time RT-PCR. The phosphorylation of p38 MAPK was evaluated by Western blotting. We found that VER-155008, an HSP70 inhibitor, enhanced the PGE1-stimulated IL-6 release and IL-6 mRNA expression. YM-08, another HSP70 inhibitor, also enhanced PGE1-stimulated IL-6 release. PD98059, a p44/p42 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, upregulated PGE1-stimulated IL-6 release. On the other hand, SB203580, a p38 MAPK inhibitor, suppressed PGE1-stimulated IL-6 release. YM-08 stimulated the PGE1-induced phosphorylation of p38 MAPK. SB203580 suppressed the amplification by YM-08 of the PGE1-stimulated IL-6 release. Our results suggest that HSP70 inhibitors upregulate the PGE1-stimulated IL-6 synthesis through p38 MAPK in osteoblasts and therefore affect bone remodeling., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kuroyanagi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Meniscal ramp lesion (RL) is the peripheral lesion of the posterior horn of the medial meniscus (PHMM) associated with anterior cruciate ligament (ACL) tear. The purpose of this study was to evaluate the accuracy of pre-operative magnetic resonance imaging (MRI) evaluation in diagnosing RL and to identify whether the difficulty in diagnosis differs depending on the location of RL., Methods: ACL-injured patients undergoing ACL reconstruction from January 2017 to January 2019 were enrolled. A methodical arthroscopic exploration to identify RL was conducted intra-operatively using three steps, namely, the anterior visualization step, the inter-condylar visualization step, and the posteromedial step. The location of the RLs was evaluated and classified into two types as follows: Red-red zone (RR) - a meniscal tear of the red-red zone of the PHMM. Menisco-capsular junction (MCJ) - a lesion at the menisco-capsular junction of the PHMM, which is more peripheral than RR. Furthermore, the accuracy of 1.5-T MRI evaluation to diagnose RL by two testers using sagittal proton-density fat-saturated images was calculated., Results: Of the 81 patients enrolled, 11 had RL: 5 cases each were at the MCJ and RR, and 1 case was at both locations. The sensitivity of MRI for detecting RL was 27.3-45.5%, whereas the specificity was 84.3-95.7% in total. The sensitivity of MRI in detecting RL at the RR and MCJ was 40.0-80.0%, 0-20.0%, respectively. The intra-observer reliability of the MRI evaluation was moderate (κ coefficient: 0.40-0.46), while the inter-observer reliability was fair to moderate (κ coefficient: 0.27-0.41)., Conclusions: A low sensitivity of the MRI in detecting RL at the MCJ was observed, and the reliability of the MRI evaluation for diagnosis of RL was not high. Therefore, methodical arthroscopic exploration is essential to diagnose RL even when it is not suspected on pre-operative MRI., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Background: We have demonstrated that epidermal growth factor (EGF)-induced migration of osteoblast-like MC3T3-E1 cells is mediated through p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase, stress-activated protein kinase/ c- Jun N-terminal kinase (SAPK/JNK), and Akt.The molecular chaperone heat shock protein 90 (HSP90) is abundantly expressed in osteoblasts. However, the role of HSP90 in osteoblast migration remains obscure., Objective: In this study, we investigated the effect of HSP90 inhibitors on the EGF-induced migration of MC3T3-E1 cells and the mechanism., Methods: Clonal osteoblast-like MC3T3-E1 cells were treated with the HSP90 inhibitors geldanamycin or onalespib and then stimulated with EGF. Cell migration was evaluated using the transwell cell migration assay and wound-healing assay. The viability of MC3T3-E1 cells was analyzed using the Cell Counting Kit-8. The phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, SAPK/JNK, Akt, and protein kinase-like endoplasmic reticulum kinase (PERK) was evaluated by western blot analysis., Results: EGF-induced migration was significantly suppressed by geldanamycin and onalespib, evaluated by both transwell cell migration assay and wound-healing assay. Geldanamycin and onalespib did not significantly alter cell viability. Geldanamycin and onalespib markedly reduced the EGF-induced phosphorylation of p44/p42 MAP kinase, but not p38 MAP kinase or Akt. By contrast, geldanamycin and onalespib increased the EGF-induced phosphorylation of SAPK/JNK. PERK phosphorylation was not significantly affected by geldanamycin or onalespib., Conclusion: Our results strongly suggest that HSP90 inhibitors reduce the EGF-induced osteoblast migration through the p44/p42 MAP kinase.

Background: Heat shock protein (HSP) 90 functions as a molecular chaperone and is constitutively expressed and induced in response to stress in many cell types. We have previously demonstrated that transforming growth factor-β (TGF-β), the most abundant cytokine in bone cells, induces the expression of HSP27 through Smad2, p44/p42 mitogen-activated protein kinase (MAPK), p38 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in mouse osteoblastic MC3T3-E1 cells. This study investigated the effects of HSP90 on the TGF-β-induced HSP27 expression and the underlying mechanism in mouse osteoblastic MC3T3-E1 cells., Methods: Clonal osteoblastic MC3T3-E1 cells were treated with the HSP90 inhibitors and then stimulated with TGF-β. HSP27 expression and the phosphorylation of Smad2, p44/p42 MAPK, p38 MAPK, and SAPK/JNK were evaluated by western blot analysis., Result: HSP90 inhibitors 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib significantly enhanced the TGF-β-induced HSP27 expression. TGF-β inhibitor SB431542 reduced the enhancement by 17-DMAG or onalespib of the TGF-β-induced HSP27 expression levels. HSP90 inhibitors, geldanamycin, onalespib, and 17-DMAG did not affect the TGF-β-stimulated phosphorylation of Smad2. Geldanamycin did not affect the TGF-β-stimulated phosphorylation of p44/p42 MAPK or p38 MAPK but significantly enhanced the TGF-β-stimulated phosphorylation of SAPK/JNK. Onalespib also increased the TGF-β-stimulated phosphorylation of SAPK/JNK. Furthermore, SP600125, a specific inhibitor for SAPK/JNK, significantly suppressed onalespib or geldanamycin's enhancing effect of the TGF-β-induced HSP27 expression levels., Conclusion: Our results strongly suggest that HSP90 inhibitors upregulated the TGF-β-induced HSP27 expression and that these effects of HSP90 inhibitors were mediated through SAPK/JNK pathway in osteoblasts., (© 2022. The Author(s).)

Objectives: We aimed to examine the psychosocial characteristics of patients with rheumatoid arthritis (RA) by remission status and determine the impacts of social support on severity of depressive symptoms., Methods: We enrolled RA patients aged 40-79 years who visited university hospitals' outpatient clinics. Severity of depressive symptoms (Beck Depression Inventory-II), physical disability (Health Assessment Questionnaire), and support were evaluated. Furthermore, RA disease activity was evaluated by 28-point Disease Activity Score (DAS28) calculation. The independent impacts of instrumental and emotional social support on depressive symptoms by remission status defined as DAS28 score < 2.6 were estimated by multivariable regression analysis., Results: This study included 360 RA patients. In the remission group, emotional support showed a statistically significant negative impact on depressive symptoms, whereas instrumental support had an extremely limited contribution to severity of depressive symptoms. In the non-remission group, instrumental support showed a negative tendency of impact on severity of depressive symptoms, whereas emotional support had a wide range of influence., Conclusions: Favourable association between emotional support and depressive symptoms is confirmed only among RA patients in remission status. The influence of emotional support in non-remission patients and that of instrumental support regardless of remission status are inconclusive., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Incretins including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted from the small intestine after oral food ingestion, are currently well-known to stimulate insulin secretion from pancreatic β-cells and used for the treatment of type 2 diabetes mellitus. We have previously reported that prostaglandin F 2α (PGF 2α ) stimulates the synthesis of interleukin-6 (IL-6) and osteoprotegerin in osteoblast-like MC3T3-E1 cells, and that IL-6 and osteoprotegerin release are mediated through the p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathways. In the present study, we investigated the effects of incretins including GLP-1 and GIP, on the PGF 2α -induced synthesis of IL-6 and osteoprotegerin and examined the detailed mechanism in osteoblast-like MC3T3-E1 cells. We found that GIP and GLP-1 significantly stimulated the PGF 2α -induced synthesis of IL-6 in osteoblast-like MC3T3-E1 cells. In addition, GIP and GLP-1 significantly enhanced the PGF 2α -induced mRNA expression levels of IL-6. On the other hand, GIP and GLP-1 markedly stimulated the PGF 2α -induced synthesis of osteoprotegerin. However, the phosphorylation of p44/p42 MAP kinase, p38 MAP kinase, or JNK induced by PGF 2α was not affected by GIP or GLP-1. Therefore, these results strongly suggest that incretins enhance the PGF 2α -induced synthesis of IL-6 and osteoprotegerin in osteoblast-like MC3T3-E1 cells. However, these syntheses are not mediated through p44/p42 MAP kinase, p38 MAP kinase, or JNK pathways., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Age at onset is one of the most important predictors of outcome following ischemic osteonecrosis (ON). Currently, there is no well-established animal model to study the effects of age on the repair process following ischemic ON. The purpose of this study was to further advance a murine model of ischemic ON using four age groups of mice to determine the effects of aging on revascularization and bone repair following ischemic ON. Ischemia was surgically induced in the distal femoral epiphysis of four age groups of skeletally immature and mature mice; juvenile (5 weeks), adolescent (12 weeks), adult (22 weeks), and middle age (52 weeks). Mice were euthanized at 2 days or 4 weeks post-ischemia surgery to evaluate the extent of ON, revascularization, and bone repair. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining showed extensive cell death in the epiphysis of all four age groups at 2 days post-ischemia surgery. At 4 weeks, the juvenile mice followed by the adolescent mice had significantly greater revascularization and repair of the necrotic marrow space, increased osteoblast and osteoclast numbers, and increased bone formation rates compared to the adult and middle-age mice. Faster revascularization and bone healing were observed in the skeletally immature mice compared to the skeletally mature mice following ischemic ON. The findings resemble the clinical observation of aging on bone repair following ischemic ON. The mouse model may serve as a useful tool to investigate the mechanisms underlying the age-related impairment of bone repair in adolescent and adult ON and to develop novel therapeutic strategies., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Hydroxyapatite (HA) augments are frequently used in orthopedic surgery. However, the effectiveness of HA augments on the treatment of intertrochanteric femoral fractures remains unknown. This study aimed to investigate whether the use of HA tubes affects the intraoperative insertion torque of the lag screw during intertrochanteric femoral fracture surgery., Methods: From January 2016 to October 2020, 58 patients with intertrochanteric femoral fractures were included and divided into the HA treatment group (HA group, n = 29) and non-HA treatment group (N group, n = 29). Patients with intertrochanteric femoral fractures were treated using the Gamma3 nail system® with or without two HA tubes. HA tubes were inserted into the femoral head through the lag screw hole before the insertion of the lag screw. The mean and maximum intraoperative insertion torques of the lag screw, bone mineral density (BMD) of the uninjured opposite side femoral neck, and tip apex distance (TAD) of the lag screw on postoperative radiographs were assessed. To assess the loss of reduction after the surgery, we investigated the amounts of telescoping of the lag screw and the changes in the neck shaft angle., Results: The mean and maximum insertion torques were correlated with BMD in the HA and N groups, respectively. The mean and maximum insertion torques were not correlated with TAD in the HA and N groups, respectively. The mean torque/BMD ratio was significantly higher in the HA group than in the N group (p = 0.03). There were no significant differences in the maximum torque/BMD ratio between HA and N groups (p = 0.06), while the maximum torque/BMD ratio tended to be higher in the HA group than in the N group. The amounts of telescoping of the lag screw in the HA group were significantly lower than that in the N group (p = 0.04), while there were no significant differences in the changes in the neck shaft angle between two groups (p = 0.32)., Conclusion: Our results strongly suggest that the use of HA tubes increases the intraoperative lag screw insertion torque/BMD ratio and may improve the lag screw fixation by strengthening the bone/metal thread interface in the treatment of intertrochanteric femoral fractures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest with the contents of this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Olive oil polyphenols, which possess cytoprotective activities like anti-oxidant and anti-inflammatory effects, could modulate osteoblast functions. The aim of this study is to elucidate the effects and the underlying mechanisms of hydroxytyrosol and oleuropein on the tumor necrosis factor-α (TNF-α)-induced macrophage colony-stimulating factor (M-CSF) and interleukin-6 (IL-6) synthesis in osteoblasts., Methods: Osteoblast-like MC3T3-E1 cells were pretreated with hydroxytyrosol, oleuropein, deguelin, PD98059 or wedelolactone, and then stimulated by TNF-α. The levels of M-CSF and IL-6 in the conditioned medium were determined with ELISA. The mRNA expression levels of M-CSF or IL-6 were determined with real-time RT-PCR. The phosphorylation levels of Akt, p44/p42 mitogen-activated protein (MAP) kinase or NF-κB in the cell lysates were determined with Western blot analysis., Results: Hydroxytyrosol and oleuropein attenuated the TNF-α-stimulated M-CSF release. Deguelin, an inhibitor of Akt, significantly suppressed the TNF-α-stimulated M-CSF release, which failed to be affected by the MEK1/2 inhibitor PD98059 or the IκB inhibitor wedelolactone. Hydroxytyrosol and oleuropein suppressed the TNF-α-induced phosphorylation of Akt and p44/p42 MAP kinase. Hydroxytyrosol and oleuropein attenuated the TNF-α-stimulated IL-6 release. Hydroxytyrosol suppressed the TNF-α-induced mRNA expressions of M-CSF and IL-6. Hydroxytyrosol or oleuropein failed to affect the cell viability., Conclusion: Our present findings strongly suggest that olive oil polyphenols hydroxytyrosol and oleuropein down-regulates TNF-α signaling at the points upstream of Akt and p44/p42 MAP kinase in osteoblasts, leading to the attenuation of M-CSF and IL-6 synthesis., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: To investigate the clinical and psychosocial backgrounds of frailty in rheumatoid arthritis (RA) patients., Methods: Patients with RA between 40 and 79 years of age who visited university hospitals in an urban area were recruited. Well-validated self-reported questionnaires were used to evaluate patient physical function (Health Assessment Questionnaire, HAQ), depressive symptoms (Beck Depression Inventory-II, BDI-II), and frailty (Kihon Checklist). A 28-point Disease Activity Score (DAS-28) was calculated to evaluate RA disease activity., Results: A total of 375 RA patients, 323 of whom were women, were enrolled (average age: 65.2 ± 9.7 years; average disease duration: 16.6 ± 11.9 years). The prevalence rates of frailty, working-age (40-64 years), young-old (65-74 years), and old-old (≥75 years) patients were 18.5, 28.8, and 36.6%, respectively. Higher age and longer disease duration were associated with frailty. Multivariable logistic regression analysis revealed that HAQ, DAS-28, and BDI-II scores were independently associated with frailty in RA patients., Conclusion: Frailty is common, even among working-age RA patients. Physical function, disease activity, and depressive symptoms were independently associated with frailty. A multidisciplinary intervention approach, along with adequate pharmacological therapy, may promote successful aging in patients with RA.

Purpose: High-grade pivot shift in the anterior cruciate ligament (ACL) injured knee is a risk factor for postoperative residual pivot shift. Procedures in addition to ACL reconstruction such as anterolateral ligament (ALL) reconstruction have been performed for patients with a high-risk of residual pivot shift. The aim of this study was to investigate the effect of the addition of ALL reconstruction to primary double-bundle ACL reconstruction in patients with preoperative high-grade pivot shift to improve stability as evaluated by quantitative measurement., Methods: Patients with ACL injuries who showed preoperative grade 3 subjective pivot shift and who underwent primary double-bundle ACL reconstruction combined with ALL reconstructions were retrospectively enrolled. Anterior tibial translation (ATT) in the Lachman test, and acceleration and external rotational angular velocity (ERAV) in the pivot shift were measured as quantitative values. Quantitative values before surgical intervention for ACL-injured knees (ACLD) and uninjured contralateral knees (intact), after temporary fixation of the isolated ACL grafts (ACLR), and subsequently after temporary fixation of both ACL and ALL grafts (ACLR + ALLR) were measured with the patient under general anaesthesia., Results: In total, 18 patients were included. The ATT was lower in ACLR and ACLR + ALLR than in intact (P = .008 and .005), while there was no significant difference between ACLR and ACLR + ALLR (P > .05). The acceleration of ACLR + ALLR was lower than that for ACLR (P = .008), while there was no significant difference between intact and ACLR or ACLR + ALLR (P > .05). The ERAV of ACLR was higher than that of intact (P < .001), while that of ACLR + ALLR was lower than that of ACLR (P < 0.001), and there was no significant difference in ERAV between intact and ACLR + ALLR (P > 0.05)., Conclusion: According to quantitative assessment of the pivot shift, the addition of ALL reconstruction to primary double-bundle ACL reconstruction improved residual knee instability and restored knee stability during surgery. Combination of ALL reconstruction with primary double-bundle ACL reconstruction was effective for patients with ACL injuries exhibiting a preoperative grade 3 subjective pivot shift., Level of Evidence: IV., (© 2021. The Author(s).)

Background: Forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide (F-u-HA/PLLA) implants are widely used in surgeries because they possess high mechanical strength, bioactivity, and radio-opacity. We previously reported that F-u-HA/PLLA implants were useful for treating lateral tibial condylar, lateral humeral condylar, and ankle fractures. The study aim was to investigate the efficacy of F-u-HA/PLLA cannulated screws and FiberLoop® for treating transverse patellar fractures., Methods: From April 2013 to February 2019, 15 patients with transverse patellar fractures were treated with F-u-HA/PLLA cannulated screws and FiberLoop® as follows: Open reduction and internal fixation (ORIF) were performed with two F-u-HA/PLLA cannulated screws and a temporary fixation Kirshner wire (K-wire). Three No. 2 FiberLoops® were inserted into these two screw holes and the K-wire hole for temporary fixation. All patients were allowed to full weight-bearing gaits using a knee brace. Knee range of motion exercise was initiated on postoperative day 1. Knee flexion was restricted to ≤90° for 1 month postoperatively. Radiograph was performed to evaluate fracture healing, screw breakage, reduction loss, and screw radio-opacity. Clinical outcomes and postoperative complications were assessed., Results: The average follow-up was 16.0 months. All fractures were successfully united. Screw breakage, reduction loss, osteolysis, and radiolucent zones around the screws were not observed at the final radiographic follow-up. All F-u-HA/PLLA screw shadows were observed during the follow-up. The average range of flexion and extension were 132.0° and -2.7°, respectively. No patients experienced deep infection episodes, late aseptic tissue reactions, or foreign body reactions postoperatively. No patients complained of pain at the final follow-up. All patients returned to their pre-injury work level and activities of daily living., Conclusion: Our results strongly suggest that ORIF with F-u-HA/PLLA screws and FiberLoop® could be an alternative treatment option for transverse patellar fractures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest with the contents of this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells., Methods: MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting., Results: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation., Conclusions: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

Resveratrol is a natural polyphenol with beneficial antioxidant properties. It suppresses the migration of osteoblast-like MC3T3-E1 cells induced by epidermal growth factor, via SIRT1-mediated inhibition of SAPK/JNK and Akt. Moreover, insulin-like growth factor-I (IGF-I) stimulates the migration involving the pathways of p44/p42 mitogen-activated protein (MAP) kinase and Akt. Therefore, we investigated the effects of resveratrol on IGF-I-induced cell migration. Resveratrol and SRT1720, an activator of SIRT1, suppressed IGF-I-induced migration. Inauhzin, a SIRT1 inhibitor, significantly rescued the inhibition of IGF-I-induced cell migration by resveratrol. Resveratrol inhibited IGF-I-induced phosphorylation of p44/p42 MAP kinase but not Akt. SRT1720 inhibited IGF-I-induced phosphorylation of p44/p42 MAP kinase. Furthermore, PD98059, p44/p42 MAP kinase inhibitor, alone suppressed IGF-I-induced osteoblast migration, but did not affect the suppressive effect of resveratrol when administered concomitantly. These findings strongly suggest that resveratrol suppresses IGF-I-induced osteoblast migration via SIRT1 activation at least partially by attenuating the p44/p42 MAP kinase pathway.

Background: The pivot-shift test is an important indicator of functional outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR). Preoperative instability as indicated by the pivot-shift test is associated with residual instability after ACLR. Few studies have used quantitative means to evaluate the pivot shift after ACLR., Purpose: To investigate the relationship between preoperative and residual instability and to identify the risk factors for residual instability by using quantitative measurements of the pivot shift., Study Design: Case-control study; Level of evidence, 3., Methods: A total of 91 patients undergoing primary double-bundle ACLR were retrospectively enrolled. Quantitative measurements of instability for ACL-deficient knees (ACLD) and uninjured contralateral knees (intact) preoperatively, as well as ACLR knees intraoperatively, were performed under general anesthesia using the pivot-shift test, with inertial sensors to measure acceleration and external rotational (ER) angular velocity. The ratios of intact to ACLD (ACLD/I) and intact to ACLR (ACLR/I) were measured. Patients who showed an ACLR/I of >1 were classified into the residual instability group, and those with an ACLR/I of ≤1 were classified into the noninstability group. Regarding demographic, surgical, and quantitative measurement factors, between-group comparisons and multivariate logistic regression were conducted for predictors of residual instability. Receiver operating characteristic curves were used to evaluate the correlations between ACLD/I and ACLR/I and the cutoff value of ACLD/I in predicting residual instability., Results: The predictive factors for intraoperative residual instability included female sex (odds ratio [OR], 0.3 [95% CI, 0.1-0.9]; P = .034) and ACLD/I for acceleration (OR, 1.6 [95% CI, 1.2-2.1]; P < .001), and ACLD/I for ER angular velocity (OR, 1.9 [95% CI, 1.2-3.1]; P = .013). Correlations between ACLD/I and ACLR/I were moderate with respect to both acceleration ( r = 0.435; P < .001) and ER angular velocity ( r = 0.533; P < .001). The cutoff points for ACLD/I were 4.9 for acceleration (sensitivity, 65.1%; specificity, 85.7%; area under the curve [AUC], 0.76) and 2.4 for ER angular velocity (sensitivity, 80.0%; specificity, 50.0%; AUC, 0.74)., Conclusion: Greater preoperative instability was a risk factor for residual instability as measured intraoperatively by a quantitatively evaluation in the pivot shift during ACL reconstruction. Quantitative measurements of instability during the pivot shift mechanism under general anesthesia may enable surgeons to predict postoperative residual instability., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Osteoprotegerin (OPG) synthesized by osteoblasts is currently considered a crucial regulator to suppress the formation and function of osteoclasts. We previously showed that the synthesis of OPG is stimulated by prostaglandin F 2α (PGF 2α ) in the involvement of p38 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c- Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK in osteoblast-like MC3T3-E1 cells. We also found that Rho-kinase is involved in the signaling of PGF 2α upstream of p38 MAPK in these cells. Tramadol is widely used to treat chronic pain, such as low back pain associated with osteoporosis. We investigated whether or not tramadol affects the OPG release induced by PGF 2α in osteoblast-like MC3T3-E1 cells. The levels of OPG in the conditioned medium were measured by an enzyme-linked immunosorbent assay. The mRNA expression of OPG was determined with real-time reverse transcription polymerase chain reaction. The phosphorylation of target protein was determined with a Western blot analysis. PGF 2α induced the release and the mRNA expression of OPG, which tramadol significantly enhanced. Morphine, a selective μ-opioid receptor (MOR) agonist, also enhanced the PGF 2α -induced OPG release. In addition, naloxone, a MOR antagonist, suppressed the enhancement by tramadol or morphine of the PGF 2α -induced OPG synthesis. Tramadol upregulated the phosphorylation of SAPK/JNK and p38 MAPK stimulated by PGF 2α but not that of p44/p42 MAPK or myosin phosphatase targeting protein (MYPT), a substrate of Rho-kinase. The inhibitors of both p38 MAPK and SAPK/JNK, SB203580 and SP600125, respectively, reduced the tramadol amplification of OPG release stimulated by PGF 2α . The present results strongly suggest that tramadol enhances the synthesis of OPG stimulated by PGF 2α through MOR in osteoblasts, and that the amplifying effect is exerted at upstream of p38 MAPK and SAPK/JNK but downstream of Rho-kinase., (© 2020 The Author(s).)

Purpose: The purpose of this study was to investigate the biomechanical function of the anterolateral structures (ALS) of the knee regarding rotational stability, and to attempt to verify the effectiveness of anterolateral ligament (ALL) reconstruction concomitant with double-bundle anterior cruciate ligament (ACL) reconstruction by quantifying the pivot shift test (PST) using an inertial sensor., Methods: Six knees of the fresh-frozen cadavers were evaluated during the following phases: (1) [Intact]; (2) ACL-deficient [ACL-D]; (3) ACL-reconstructed [ACL-R]; (4) ACL-reconstructed + ALS-deficient [ACL-R + ALS-D]; and (5) combined ACL and ALL reconstructed [ACL-R + ALL-R]. We evaluated knee rotational instability during each phase using the PST. We used an inertial sensor to calculate tibial external rotational angular velocity (ERAV) and tibial acceleration. Data were analyzed using repeated-measures analysis of variance; statistical significance was accepted as P < 0.05., Results: Relative to [Intact], [ACL-D] caused a significant increase in ERAV and acceleration. However, there was no difference in these parameters between [ACL-R] and [Intact]. [ACL-R + ALS-D] increased ERAV significantly compared with [ACL-R], and there was a significant difference between ERAV during [ACL-R + ALS-D] and [Intact]. However, ERAV was significantly reduced during [ACL-R + ALL-R] compared with [ACL-R + ALS-D], and there was no significant difference in ERAV or acceleration between [ACL-R + ALL-R] and [Intact]., Conclusions: ALS controlled rotational instability in cooperation with the ACL in a cadaveric model. In cases of combined injury of ACL and ALS, concomitant ACL and ALL reconstruction may restore knee stability comparable with the intact state., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Incretins, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), secreted from enteroendocrine cells after food ingestion, are currently recognized to regulate glucose metabolism through insulin secretion. We previously demonstrated that platelet-derived growth factor-BB (PDGF-BB) induces the migration of osteoblast-like MC3T3-E1 cells through mitogen-activated protein (MAP) kinases, including p38 MAP kinase. In the present study, we investigated whether or not incretins affect the osteoblast migration. The PDGF-BB-induced cell migration was significantly reinforced by GLP-1, GIP or cAMP analogues in MC3T3-E1 cells and normal human osteoblasts. The upregulated migration by GLP-1 or cAMP analogues was suppressed by H89, an inhibitor of protein kinase A. The amplification by GLP-1 of migration induced by PDGF-BB was almost completely reduced by SB203580, a p38 MAP kinase inhibitor in MC3T3-E1 cells and normal human osteoblasts. In addition, GIP markedly strengthened the PDGF-BB-induced phosphorylation of p38 MAP kinase. Exendin-4, a GLP-1 analogue, induced Rho A expression and its translocation from cytoplasm to plasma membranes in osteoblasts at the epiphyseal lines of developing mouse femurs in vivo. These results strongly suggest that incretins accelerates the PDGF-BB-induced migration of osteoblasts via protein kinase A, and the up-regulation of p38 MAP kinase is involved in this acceleration. Our findings may highlight the novel potential of incretins to bone physiology and therapeutic strategy against bone repair.

Heat shock protein (HSP) 90 that is ubiquitously expressed in various tissues is a major molecular chaperone. We have previously demonstrated that prostaglandin D 2 (PGD 2 ), a bone remodeling factor, elicits the expression of HSP27, a small HSP, through stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of HSP90 in the PGD 2 -stimulated HSP27 induction and the underlying mechanism in MC3T3-E1 cells. Onalespib, an inhibitor of HSP90, significantly enhanced the PGD 2 -stimulated HSP27 induction. In addition, geldanamycin, another HSP90 inhibitor, potentiated the HSP27 induction. Both onalespib and geldanamycin markedly amplified the PGD 2 -induced phosphorylation of SAPK/JNK and p38 MAP kinase. SP600125, an inhibitor of SAPK/JNK, and SB203580, an inhibitor of p38 MAP kinase, suppressed the amplification by onalespib of the PGD 2 -stimulated HSP27 induction. These results strongly suggest that HSP90 plays a negative role in the HSP27 induction stimulated by PGD 2 in osteoblasts, and that the inhibitory effect of HSP90 is mediated through the regulation of SAPK/JNK and p38 MAP kinase., (Copyright © 2019. Published by Elsevier Inc.)

Heat shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone in a variety of cells including osteoblasts. We previously showed that insulin-like growth factor-I (IGF-I) elicits migration of osteoblast-like MC3T3-E1 cells through the activation of phosphatidylinositol 3-kinase/Akt and p44/p42 mitogen-activated protein (MAP) kinase. In the present study, we investigated the effects of HSP70 inhibitors on the IGF-I-elicited migration of these cells and the mechanism involved. The IGF-I-stimulated osteoblast migration evaluated by a wound-healing assay and by a transwell cell migration was significantly reduced by VER-155008 and YM-08, which are both HSP70 inhibitors. VER-155008 markedly suppressed the IGF-I-induced phosphorylation of p44/p42 MAP kinase without affecting that of Akt. In conclusion, our results strongly suggest that the HSP70 inhibitor reduces the IGF-I-elicited migration of osteoblasts via the p44/p42 MAP kinase., Competing Interests: The authors declare that they have no conflicts of interest.

Legg-Calvé-Perthes disease (LCPD) is a childhood form of ischemic osteonecrosis of the femoral head which can produce a permanent femoral head deformity and early osteoarthritis. The femoral head deformity results from increased bone resorption and decreased bone formation during repair and remodeling of the necrotic femoral head. A recent study showed that a pro-inflammatory cytokine, interleukin-6 (IL-6), is significantly elevated in the synovial fluid of patients with LCPD. We hypothesized that IL-6 elevation decreases bone formation during the repair process following ischemic osteonecrosis and that IL-6 depletion will increase new bone formation. To test this hypothesis, we surgically induced ischemic osteonecrosis in the wild-type (n = 29) and IL-6 knockout (KO) mice (n = 25). The animals were assessed at 48 h, 2 weeks and 4 weeks following the induction of ischemic osteonecrosis using histologic, histomorphometric and micro-CT methods. IL-6 immunohistochemistry showed high expression of IL-6 in the osteonecrotic side of the wild-type mice at 48 h and 4 weeks following ischemic osteonecrosis, but not in the IL-6 KO mice. We also confirmed an undetectable level of IL-6 expression in the primary osteoblasts of the IL-6 KO mice compared to the readily detectable level in the wild-type mice. Furthermore, we confirmed that IL-6 deletion did not affect the extent of bone necrosis in the IL-6 KO mice compared to the wild-type mice by performing histologic and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assessments at 2 weeks following the induction of ischemia. Both groups had the same extent of ischemic osteonecrosis and absence of repair at 2 weeks. At 4 weeks, the necrotic epiphyses showed a significant increase in the extent of revascularization in the IL-6 KO mice compared to the wild-type mice (p = 0.001). In addition, a significantly greater recovery of the hematopoietic bone marrow was observed in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice (p < 0.01). Vascular endothelial growth factor (VEGF) immunohistochemistry showed regionally increased staining in the areas of repair in the osteonecrosis side of IL-6 KO mice compared to the wild-type mice at 4 weeks following ischemic osteonecrosis. Micro-CT assessment of the wild-type mice at 4 weeks showed a significant decrease in the percent bone volume (p < 0.01) in the osteonecrotic side compared to the control side. In contrast, IL-6 KO mice showed significantly increased bone volume in the osteonecrotic side compared to the osteonecrotic side of WT mice (p < 0.001). No significant difference in the bone volume percentage was found between the control side of the wild-type and the IL-6 KO mice. Histomorphometric analysis at 4 weeks revealed increased osteoblast number/bone surface (p < 0.001), bone formation rate (BFR) (p = 0.0001), and mineral apposition rate (MAR) (p < 0.0001) in the osteonecrotic side of the IL-6 KO mice compared to the wild-type mice. The number of osteoclast/bone surface was also increased in the IL-6 KO mice compared to the wild-type mice (p < 0.0001). No significant difference was observed between the control side of the wild-type and IL-6 KO mice with regards to the number of osteoblast or osteoclast/bone surface, BFR, and MAR. We next obtained primary osteoblasts from IL-6 KO mice and showed they expressed a significantly higher level of RANKL/OPG than wild-type mice (p = 0.001) in hypoxia culture condition. Taken together, the findings indicate that IL-6 deletion stimulates revascularization and new bone formation following ischemic osteonecrosis. This study provides new evidence that therapeutic strategies to block IL-6 may be beneficial for bone healing following ischemic osteonecrosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide (F-u-HA/PLLA) devices possess high mechanical strength, bioactivity, and radio-opacity. The aim of this study was to assess the efficacy of F-u-HA/PLLA screws in the treatment of lateral tibial condylar fractures. From January 2005 to December 2010, a total of 7 patients with displaced closed lateral tibial condylar fractures (Schatzker type II) were treated using F-u-HA/PLLA screws. Open reduction and internal fixation was performed using 2 or 3 F-u-HA/PLLA screws. After surgery, weight bearing was not allowed for 6 weeks. Range of motion exercise was initiated after removal of the plaster splint. Radiographs were evaluated for fracture healing, joint depression, and the radioopacity of F-u-HA/PLLA screws. Clinical outcomes and postoperative complications were also assessed. Average follow-up was 44 months. All fractures were successfully healed. Average values for joint depression were 4.7 mm (range, 2-9 mm) preoperatively, 0.4 mm (range, 0-1 mm) postoperatively, and 0.4 mm (range, 0-1 mm) at final follow-up. Whole shadows of F-u-HA/PLLA screws were observed during the follow-up period. Breakage of screws, osteolysis, and a radiolucent zone around the screws were not observed at final follow-up. Average knee flexion and extension were 134° (range, 110° to 150°) and -1° (range, -10° to 0°), respectively. No patient had wound infection, late aseptic tissue response, or foreign body reaction postoperatively. None of the patients reported pain at final follow-up. These results suggest that F-u-HA/PLLA screws could be an alternative option for the treatment of lateral tibial condylar fractures. [Orthopedics. 2018; 41(3):e365-e368.]., (Copyright 2018, SLACK Incorporated.)