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Background: In comparison to static spacers, articulating spacers have been shown to result in a similar infection eradication rate in two-stage revision of periprosthetic knee infections. However, the optimal construct for articulating spacers has not been identified yet. The aim of this study was to present a preliminary result of treatment for periprosthetic knee infection using a novel computer-aided design (CAD)-articulating spacer. Methods: We retrospectively reviewed 32 consecutive cases of chronic periprosthetic knee infection occurring from January 2015 to December 2015. In these cases, we used an antibiotic-loaded, optimized CAD-articulating spacer based on the retrieved knee prosthesis. Evaluation included infection eradication rate, the Hospital of Special Surgery (HSS) knee score, range of motion (ROM), and spacer-related mechanical complications. All cases were regularly followed-up for 2 years minimum. Results: Twenty-eight of 32 patients (87.5%) had infection eradication; 18 patients (56.3%) received reimplantation successfully. The mean interval between spacer insertion and reimplantation was 8.8 months (range 4.0–12.5 months). The mean HSS knee score and ROM significantly increased during each interval (p < 0.0001 for both). The mean HSS knee scores were 31.2 (range 20–48) at initial visit, 65.4 (range 60–78.8) at 1 month after spacer insertion, and 84.2 (range 78–90) at 3 months after reimplantation (p < 0.0001). The mean ROM were 72.0° (range 15–100°), 85.6° (range 35–110°), and 102.0° (range 80–122°), respectively (p = 0.002). Two (6.3%) spacer-related mechanical complications occurred. Conclusions: The CAD-articulating spacer in two-staged revision of periprosthetic knee infection significantly controlled infection, improved clinical outcomes, increased ROM, and decreased mechanical complications in the preliminary study. Further larger clinical studies are needed to confirm the findings presented here. [ABSTRACT FROM AUTHOR]

Background. Cholangitis is the infectious disease involving the biliary tract, which may induce systemic inflammation. Bone loss is a well-known sequelae after systemic inflammatory disease, and one grave complication after osteoporosis is hip fracture. We want to know whether cholangitis can contribute to increased risk of hip fracture. Methods. All the patients diagnosed with cholangitis since January 1, 2001, to December 31, 2009, were assessed. All the subjects with cancer history, traumatic accident, and previous fracture were excluded. We selected the controls without cholangitis and matched the controls to cholangitis patients by age, sex, osteoporosis, and the use of steroid for more than 30 days by approximately 1:4 ratio. Results. There were 2735 subjects in the cholangitis cohort and 10915 in the noncholangitis cohort. There were 101 hip fractures in the cholangitis cohort with the incidence density of 7.58 per 1000 person-years. As for the noncholangitis cohort, 366 individuals suffered from hip fracture with the incidence density of 5.86 per 1000 person-years. The risk of hip fracture was higher in the cholangitis cohort with a 1.29-fold increased risk than the noncholangitis cohort (hazard ratio = 1.29, 95% confidence interval = 1.03-1.61). The association between cholangitis and the hip fracture was more prominent among subjects less than 65 years (hazard ratio = 2.65, 95% confidence interval =1.30-5.39) and the subjects without comorbidities (hazard ratio = 3.01, 95% confidence interval = 1.42-6.41). Conclusions. Cholangitis is associated with higher risk for hip fracture, especially among young subjects free from medical comorbidities. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is a well-established modality for the treatment of advanced knee osteoarthritis (OA). However, the detrimental effects of intramedullary reaming used in conventional TKA for distal femur cutting are of concern. Avoiding intramedullary reaming with the use of computer-assisted navigation TKA can not only provide superior prosthetic alignment, but also mitigate perioperative blood loss and the dissipation of marrow emboli. We quantified local and systemic concentrations of inflammation markers for both techniques. Forty-four participants undergoing computer-assisted navigation and 53 receiving conventional TKA for advanced knee OA were recruited between 2013/02/08 and 2015/12/09. Blood samples were collected from all participants at baseline then again at 24 and 72 hours postoperatively and analyzed by ELISA for interleukin 6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-β1); these markers were also measured in Hemovac drain fluid collected at 24 and 72 hours. Serum levels of IL-6, IL-10, TNF-α and TGF-β1(unit for all markers: pg/mL) were increased from baseline by smaller increments in the navigation TKA cohort compared with the conventional TKA group at 24 hours (17.06 vs 29.39, p = 0.02; 0.51 vs 0.83, p = 0.16; –0.04 vs 0.36, p < 0.01 and –48.18 vs 63.24, p< 0.01, respectively) and at 72 hours (12.27 vs 16.87, p = 0.01; –0.40 vs 0.48, p < 0.01; 0.58 vs 0.98, p = 0.07 and –55.16 vs 63.71, p < 0.01, respectively). IL-10 levels in drainage fluids collected 24 hours after TKA were also significantly lower in the navigation group versus the conventional TKA group (8.55 vs 12.32, p < 0.01). According to our evidence, the merits of computer-assisted navigation TKA are augmented by low levels of inflammation markers. [ABSTRACT FROM AUTHOR]

Abstract: Background: Concomitant ipsilateral femoral shaft and neck fractures present a challenge to the orthopaedic surgeon, and no consensus has yet emerged on the optimal treatment method. We report the results of a retrospective study of 43 patients with these complex fractures who were treated at a single Level 1 trauma centre. Patients and methods: The study participants consisted of 28 males and 15 females with a mean age of 43 years. The mean follow-up period was 48 months. Four different treatment methods were used: (1) antegrade reamed intramedullary nailing of the shaft with cancellous screw fixation of the neck, (2) dynamic hip screw (DHS) fixation of the neck and low-contact dynamic compression plate (LCDCP) fixation of the shaft, (3) cancellous screw fixation of the neck and LCDCP fixation of the shaft, and (4) reconstruction nailing of both shaft and neck. Results: No statistically significant differences in amount of blood loss, duration of surgery, total complication rate, nor clinical results were found among the four treatment methods. For femoral neck fracture, however, the complication rate of cannulated screw with antegrade intramedullary nailing fixation was 11 times that of DHS with LCDCP fixation. Conclusions: Antegrade nail with screw fixation is not a recommended treatment method in patients with ipsilateral femoral shaft and neck fractures. [Copyright &y& Elsevier]

Abstract: It has been shown that ultrasound (US) stimulation accelerates fracture healing in the animal models and in clinical studies. However, the precise molecular events generated by US in chondrocytes have not been clarified well. Here we found that US stimulation transiently increased the surface expression of α2, α5, β1 or β3 but not α3 or α4 integrins in human chondrocytes, as shown by flow cytometric analysis. US stimulation increased prostaglandin E2 formation as well as the protein and mRNA levels of cyclooxygenase-2 (COX-2). At the mechanistic level, anti-integrin β1 and β3 antibodies or β1 and β3 integrin small interference RNA attenuated the US-induced COX-2 expression. Integrin-linked kinase (ILK) inhibitor (KP-392), Akt inhibitor, NF-κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited the potentiating action of US. US stimulation promotes kinase activity of ILK, phosphorylation of Akt. In addition, US stimulation also induces IKKα/β phosphorylation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation at Ser276, p65 and p50 translocation from the cytosol to the nucleus, and κB-luciferase activity. The binding of p65 to the NF-κB element, as well as the recruitment of p300 and the enhancement of p50 acetylation on the COX-2 promoter was enhanced by US. Taken together, our results provide evidence that US stimulation increases COX-2 expression in chondrocytes via the integrin/ILK/Akt/NF-κB and p300 signaling pathway. [Copyright &y& Elsevier]

Nerve sheath ganglion is a relatively rare clinical entity commonly found in the peroneal nerve in the lower limb or the ulnar nerve in the upper extremity. It is rarely found in the tibial nerve. The occurrence of a nerve sheath ganglion in a patient's tibial nerve has been identified. The initial presentation of the tumor mass has been very similar to that of a Baker's cyst, namely a soft undulating popliteal mass. Yet, the case also presented symptoms and signs of tibial nerve compressive neuropathy. We present here a rare case of nerve sheath ganglion of the tibial nerve. Clinical courses of the patient were reviewed, and relevant issues were discussed with a thorough literature review. [ABSTRACT FROM AUTHOR]

Articular cartilage is the primary structure in joints which is responsible for withstanding compressive loading; however, it is possible that cartilage also experiences localized tensile loading under various loading and boundary conditions. To date, little is known as to whether chondrocyte functions are dependent on the loading variation, especially when loading is switched from compression to tension. The purpose of this study is to examine the metabolism of chondrocytes under both compressive and tensile loadings in vitro. Our results suggest that synthesis of both collagen II and aggrecan is regulated differently by compression and tension at the mRNA level. Tensile loading significantly inhibited the mRNA expression of both collagen II and aggrecan. Since poor content of collagen II and proteoglycan has been considered a detrimental factor in the integrity of cartilage matrix, cartilage degradation and the possible formation of osteoarthritis may be the consequence of loading patterns switching from compression to tension. [ABSTRACT FROM AUTHOR]

Abstract: A retrospective study was performed to evaluate the use of an AO reconstruction plate in open reduction and internal fixation for non-union of the mid-shaft clavicle, examining the relationship between the position of the scapula and final functional results and whether perioperative variables such as clavicular reconstruction ratio and period of non-union influence the position of the scapula. From January 1998 to January 2005, data on 21 people with symptomatic non-union of the mid-shaft clavicle were collected; 17 non-unions were atrophic and 4 were hypertrophic. Initially, treatment was conservative with a figure-of-eight bandage in 19 cases, and cerclage wire fixation in 2 cases. The follow-up period was 65.7 (24–108) months. Outcome analyses included standard clinical follow-up, plain radiography, the Constant–Murley scoring and subjective assessment. All non-unions united well in 13.6 (11–27) weeks. All patients were satisfied with their surgical results. Greater age and longer period of non-union resulted in a larger amount of scapular malposition, which related to poor functional results. [Copyright &y& Elsevier]

Abstract: Background: Use of functional knee braces has been suggested to provide protection and to improve kinetic performance of the knee in anterior cruciate ligament-injured patients. However, the efficacy of knee bracing in achieving these goals is still controversial. The purpose of this study was to examine the immediate effects of functional bracing on the three-dimensional kinetics of the knee in individuals with anterior cruciate ligament injuries during level walking. Methods: Fifteen anterior cruciate ligament-deficient and 15 anterior cruciate ligament-reconstructed subjects were each fitted with a DonJoy Goldpoint brace and walked at a self-selected pace, first without and then with the brace. Kinematic and kinetic data were measured and three-dimensional joint moments and angular impulses at the knee were calculated and compared between bracing conditions and between limbs. Findings: Functional knee bracing did not significantly affect the kinetics of the unaffected knees for either group. Bracing significantly increased the peak abductor moments in anterior cruciate ligament-deficient knees and reduced the bilateral kinetic asymmetry in the coronal plane. For the anterior cruciate ligament-reconstructed group, bracing increased peak moments and impulses of the abductors and extensors. It also reduced bilateral kinetic asymmetry in the sagittal and coronal planes. Interpretation: Effects of the knee brace were apparent in the coronal plane for both anterior cruciate ligament-deficient and anterior cruciate ligament-reconstructed patients, and in the sagittal plane for anterior cruciate ligament-reconstructed patients. Functional bracing can be recommended for anterior cruciate ligament-reconstructed patients to assist in achieving better bilateral kinetic symmetry during gait. For anterior cruciate ligament-deficient patients, apart from bracing, additional emphasis on the rehabilitative training for better kinetic knee performance in the sagittal plane is needed. [Copyright &y& Elsevier]

Autologous chondrocyte transplantation (ACT) is a promising method to treat chondral and osteochondral defects. This study introduced a modified method for cell culture in ACT. Porcine chondrocytes were cultured for 3 weeks under low hydrostatic pressure at 250 Pa. The results showed that the dry weight of the cartilage-like membrane in the loading group was 3.0 times more than the control group (no loading) ( p ), and cell numbers were significantly increased by 3.1 times ( p ) after a 3-week culture. Compared with the fresh tissue sample, the mRNA expression of collagen II was not statistically different and the mRNA of aggrecan was only slightly decreased by 19%. These data suggest that the hydrostatic pressure at this level significantly increased the cell numbers and biosynthesis of cultured chondrocytes. [ABSTRACT FROM AUTHOR]

Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07–1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00–1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0–26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2–67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42–5.56). Preventive measures for hip fracture might be warranted for PLA patients. [ABSTRACT FROM AUTHOR]

Surgical interventions for congenital scoliosis are challenging for spine surgeons. The coordination of 3-dimensional (3D), real-time, image-guided navigation with an ultrasonic bone cutter allows surgeons to localize the affected area of the spine accurately and remove the lesion without damaging soft tissue structures. The goal of this technical paper is to report a previously undescribed method of hemivertebrectomy that combines 3D, real-time, image-guided navigation and an ultrasonic bone cutter. We highlight the feasibility and safety of this method in spinal surgery. Three patients with congenital scoliosis were treated with this technique. We present three illustrative cases comprising hemivertebrectomies for congenital scoliosis. Intraoperative photos demonstrating the technique are also provided. All surgeries were completed without complications. The hemivertebrae were completely removed, and marked correction of congenital scoliosis was noted. We believe that the combination of 3D, real-time image navigation and an ultrasonic bone cutter improves hemivertebrectomy by increasing accuracy and avoiding dura laceration, major organ damage, or potential vessel damage. [ABSTRACT FROM AUTHOR]

Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07–1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00–1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0–26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2–67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42–5.56). Preventive measures for hip fracture might be warranted for PLA patients. [ABSTRACT FROM AUTHOR]

Background. Osteoporosis and fragility fracture are the major complications after liver transplantation (LT). The aim of the study was to determine the incidence and risk factors of hip fracture after LT. Methods. We conducted a retrospective population-based cohort study, enrolling the patients receiving LT between January 1999 and December 2010. Control subjects were randomly matched to every recipient by age and sex by 1 : 10 ratios. Results. During the follow-up period, 17 recipients (0.77%) and 70 (0.32%) control subjects suffered from hip fractures. The incident rates (per 10000 person-years) were 21.49 for recipients and 7.52 for controls (adjusted hazard ratio = 2.71; 95% confidence interval = 1.21–6.05). The cumulative incidence of hip fracture was significantly higher among the recipients (p < 0.0001). Among the recipients, the subjects aged >65 years at transplantation and with pretransplant steroid use are more susceptible to posttransplant hip fracture. Immunosuppressive agents did not significantly affect the risk of hip fracture among recipients. Conclusions. Liver transplantation is a risk factor for hip fractures. Aged >65 years at transplantation and pretransplant steroid use are risk factors for posttransplant hip fractures among the recipients. [ABSTRACT FROM AUTHOR]

Background. The pedicle screw is one of the main tools used in spinal deformity correction surgery. Robotic and navigated surgeries are usually used, and they provide superior accuracy in pedicle screw placement than free-hand and fluoroscopy-guided techniques. However, their high cost and space limitation are problematic. We provide a new solution using 3D printing technology to facilitate spinal deformity surgery. Methods. A workflow was developed to assist spinal deformity surgery using 3D printing technology. The trajectory and profile of pedicle screws were determined on the image system by the surgical team. The engineering team designed drill templates based on the bony surface anatomy and the trajectory of pedicle screws. Their effectiveness and safety were evaluated during a preoperative simulation surgery. The surgery consisted in making a pilot hole through the drill template on a computed tomography- (CT-) based, full-scale 3D spine model for every planned segment. Somatosensory evoke potential (SSEP) and motor evoke potential (MEP) were used for intraoperative neurophysiological monitoring. Postoperative CT was obtained 6 months after the correction surgery to confirm the screw accuracy. Results. From July 2015 to November 2016, we performed 10 spinal deformity surgeries with 3D printing technology assistance. In total, 173 pedicle screws were implanted using drill templates. No notable change in SSEP and MEP or neurologic deficit was noted. Based on postoperative CT scans, the acceptable rate was 97.1% (168/173). We recorded twelve pedicle screws with medial breach, six with lateral breach, and five with inferior breach. Medial breach (12/23) was the main type of penetration. Lateral breach occurred mostly in the concave side (5/6). Most penetrations occurred above the T8 level (69.6%, 16/23). Conclusion. 3D printing technology provides an effective alternative for spinal deformity surgery when expensive medical equipment, such as intraoperative navigation and robotic systems, is unavailable. [ABSTRACT FROM AUTHOR]

Background. Osteonecrosis of the femoral head (ONFH) contributes to 45% of total hip replacements (THRs) annually in Taiwan. Nontraumatic ONFH (NONFH) is multifactorial; no effective Western medicine is available to delay the disease process. This population-based cohort study investigated the association of traditional Chinese medicine (TCM) therapy with risk of THR in patients with NONFH. Methods. This retrospective study was conducted using claims data from all insured residents covered by the National Health Insurance from 2000 to 2010. We enrolled 1,680 newly diagnosed ONFH patients who had not undergone THR, before or within 6 months after diagnosis of ONFH; these patients did not exhibit hip fracture or dislocation before the endpoint. In total, 595 propensity score-matched pairs were selected from among 1,028 TCM users and 652 non-TCM users. The association between TCM use and risk of THR was analyzed using a Cox proportional hazard model. Kaplan-Meier and log rank tests were performed to plot the cumulative incidence of THR. Results. The mean follow-up periods were 5.00 years and 3.57 years for TCM and non-TCM cohorts, respectively. Compared to the non-TCM cohort, the TCM cohort had fewer patients undergoing THR surgery (25.4% vs. 18.2%, adjusted hazard ratio: 0.60, p<0.0001). The risk of reduction was noted in the group aged 30–59 years (adjusted hazard ratio: 0.56, p<0.0001), but there was no association with gender nor socioeconomic status. There was a significantly lower cumulative incidence of THR in TCM users (p<0.0001). Shu-Jing-Huo-Xue-Tang and Yan Hu Suo were the most frequently prescribed formula and single herb, respectively. Conclusions. NONFH patients using TCM had a lower risk of THR; the risk of reduction was noted in the group aged 30–59 years but was not associated with gender nor socioeconomic status. TCM might be useful in conservative treatment for NONFH. [ABSTRACT FROM AUTHOR]

Repairing damaged articular cartilage is particularly challenging because of the limited ability of cartilage to perform self-repair. Intra-articular injections of N-acetylglucosamine (GlcNAc) comprise a method of repairing full-thickness articular cartilage defects in the rabbit knee joint model. To date, the effects of administration of GlcNAc and hyaluronic acid (HA) have been investigated only in the context of osteoarthritis treatment. Therefore, we evaluated the therapeutic effects of using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants and intra-articular injections of GlcNAc or HA in a rabbit model of osteochondral regeneration to investigate whether they have the potential for inducing osteochondral regeneration when used alone or simultaneously. Twenty-four rabbits were randomized into one of four groups: the scaffold-only group (PLGA), the scaffold with intra-articular injections of GlcNAc (PLGA+G) group, twice per week for four weeks; the scaffold with intra-articular injections of HA group (PLGA+HA) group, once per week for three weeks; and the scaffold with intra-articular injections of GlcNAc and HA (PLGA+G+HA) group, once per week for three weeks. Knees were evaluated at 4 and 12 weeks after surgery. At the end of testing, only the PLGA+G+HA group exhibited significant bone reconstruction, chondrocyte clustering, and good interactions with adjacent surfaces at 4 weeks. Additionally, the PLGA+G+HA group demonstrated essentially original hyaline cartilage structures that appeared to have sound chondrocyte orientation, considerable glycosaminoglycan levels, and reconstruction of the bone structure at 12 weeks. Moreover, the PLGA+G+HA group showed organized osteochondral integration and significantly higher bone volume per tissue volume and trabecular thickness. However, there were no significant differences between the PLGA+G and PLGA+HA groups except for gap formation on subchondral bone in the PLGA+G group. This study demonstrated that PLGA implantation combined with intra-articular injections of GlcNAc and HA allowed for cartilage and bone regeneration and significantly promoted osteochondral regeneration in rabbits without supplementation of exogenous growth factors. And the combination of this two supplements with PLGA scaffold could also prolong injection interval and better performance than either of them alone for the reconstruction of osteochondral tissue in the knee joints of rabbits. [ABSTRACT FROM AUTHOR]

Purposes: To propose a new model‐based tracking method for measuring three‐dimensional (3D) dynamic joint kinematics using a clinical alternating biplane x‐ray imaging system; and to quantify in vitro its errors in measuring ankle and knee motions at different motion speeds. Methods: A new model‐based tracking method based on motion component partition and interpolation (MCPI) was developed for measuring 3D dynamic joint kinematics based on a clinical alternating biplane x‐ray imaging system. Two detectors of the biplane imaging system placed perpendicular to each other were operated to collect alternating fluoroscopic images of the targeted joint during tasks. The CT data of the joint were also acquired for the reconstruction of volumetric and surface models of each of the associated bones. The CT‐based models of the bones were first registered to the alternating images using a model‐to‐single‐plane fluoroscopic image registration method, and the resulting bone poses were then refined using a two‐level optimization with motion component partition and model vertex trajectory interpolation. The MCPI method was evaluated in vitro for measurement errors for an ankle and a knee specimen moving at different speeds against a standard reference provided by a highly accurate motion capture system. The positional and rotational errors of the measured bone poses were quantified in terms of the bias, precision, and root‐mean‐squared errors (RMSE), as well as the mean target registration error (mTRE), a final mTRE less than 2.5 mm indicating a successful registration. Results: The new method was found to have RMSE of bone pose measurements of less than 0.18 mm for translations and 0.72° for rotations for the ankle, and 0.33 mm and 0.74° for the knee with a high successful registration rate (>97%), and did not appear to be affected by joint motion speeds. Given the same alternating fluoroscopic images, the MCPI method outperformed the typical biplane analysis method assuming zero time offset between the two fluoroscopic views. The differences in performance between the methods were increased with increased joint motion speed. With the accurate bone pose data, the new method enabled talocrural, subtalar, and tibiofemoral kinematics measurements with submillimeter and subdegree accuracy, except for an RMSE of 1.04° for the internal/external rotation of the talocrural joint. Conclusions: A new model‐based tracking method based on MCPI has been developed for measuring dynamic joint motions using an alternating biplane x‐ray imaging system widely available in medical centers. The MCPI method has been demonstrated in vitro to be highly accurate in determining the 3D kinematics of the bones of both the ankle joint complex and the knee. The current results suggest that the MCPI method would be an effective approach for measuring in vivo 3D kinematics of dynamic joint motion in a clinical setting equipped with an alternating biplane x‐ray imaging system. [ABSTRACT FROM AUTHOR]

Chemokine C-C motif ligand 4 (CCL4) gene is a chemokine-encoding gene, and the polymorphism of CCL4 gene has been shown to predict risk of various diseases. We want to investigate whether the single nucleotide polymorphisms (SNPs) of the CCL4 gene can predict the risk of rheumatoid arthritis (RA). Between 2007 and 2015, we recruited 217 patients diagnosed with RA and 371 control participants. Comparative genotyping of the rs1634507, rs10491121, and rs1719153 SNPs was performed. When compared with participants with the A/A genotype of rs1719153, those with the A/T genotype were less likely to develop RA, as were those with the A/T+T/T genotype. The protective effect of the T-containing genotype was even more prominent among females. Those with A/T in rs1719153 were 56% less likely to develop RA compared with females with A/A; a similar protective effect was seen for females with the A/T+T/T genotype compared with those with A/A. The GTEx database revealed that patients carrying the T/T genotype had lower levels of CCL4 gene expression than those carrying the A/A genotype. These results indicate that the nucleotide T over the rs1719153 is associated with decreased CCL4 gene expression and decreased risk for RA. [ABSTRACT FROM AUTHOR]

Soft tissue artefacts (STA) are a major error source in skin marker-based measurement of human movement, and are difficult to eliminate non-invasively. The current study quantified in vivo the STA of skin markers on the thigh and shank during cycling, and studied the effects of knee angles and pedal resistance by using integrated 3D fluoroscopy and stereophotogrammetry. Fifteen young healthy adults performed stationary cycling with and without pedal resistance, while the marker data were measured using a motion capture system, and the motions of the femur and tibia/fibula were recorded using a bi-plane fluoroscopy-to-CT registration method. The STAs with respect to crank and knee angles over the pedaling cycle, as well as the within-cycle variations, were obtained and compared between resistance conditions. The thigh markers showed greater STA than the shank ones, the latter varying linearly with adjacent joint angles, the former non-linearly with greater within-cycle variability. Both STA magnitudes and within-cycle variability were significantly affected by pedal resistance ( p < 0.05). The STAs appeared to be composed of one component providing the stable and consistent STA patterns and another causing their variations. Mid-segment markers experienced smaller STA ranges than those closer to a joint, but tended to have greater variations primarily associated with pedal resistance and muscle contractions. The current data will be helpful for a better choice of marker positions for data collection, and for developing methods to compensate for both stable and variation components of the STA. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis of painful cemented vertebrae resulting from failed PV is not clearly defined in literature. This report evaluates the effectiveness of modified dynamic radiographs in diagnosing painful cemented vertebrae resulting from failed PV.Methods: From January 2011 to June 2015, 345 patients with a total of 399 VCFs underwent PV at our institution. Among the 345 patients, 27 patients underwent repeated PV at the cemented vertebrae because of persisting or recurrent pain after vertebroplasty. The prevertebroplasty examinations included routine radiographs, modified dynamic radiographs, and MRI. Kyphotic angles and the anterior vertebral body height (AVBH) were measured. The image findings in routine radiographs, modified dynamic radiographs, and MRI were compared. Finally, a visual analog scale was used to measure the outcome.Results: The patients ranged in age from 67 to 90 years. MRI revealed a moderate amount of fluid (definite diagnosis of refracture) in the cemented vertebrae in seven patients, bone edema without fluid in nine patients, and bone edema with minimal fluid in ten patients. The rate of diagnosis of painful cemented vertebrae according to MRI was 27% (7/26). The difference in the kyphotic angle between sitting and supine cross-table lateral radiographs was -9.36° ± 5.20° (P < 0.001). The difference in AVBH was 8.08 ± 3.21 mm (P < 0.001). All 27 patients were confirmed to have dynamic mobility according to the modified dynamic radiographs.Conclusions: When the diagnosis of painful cemented vertebrae is questionable, modified dynamic radiographs can help diagnose painful cemented vertebrae resulting from failed PV. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is manifested by synovial inflammation and cartilage destruction that is directly linked to synovitis, joint swelling and pain. In the light of the role of synovium in the pathogenesis and the symptoms of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms and progression of OA. Transforming growth factor beta 1 (TGF-β1), a secreted homodimeric protein, possesses unique and potent anti-inflammatory and immune-regulatory properties in many cell types. Heme oxygenase 1 (HO-1) is an inducible anti-inflammatory and stress responsive enzyme that has been proven to prevent injuries caused by many diseases. Despite the similar anti-inflammatory profile and their involvement in the pathogenesis of arthritic diseases, no studies have as yet explored the possibility of any association between the expression of TGF-β1 and HO-1. Methodology/Principal findings: TGF-β1-induced HO-1 expression was examined by HO-1 promoter assay, qPCR, and Western blotting. The siRNAs and enzyme inhibitors were utilized to determine the intermediate involved in the signal transduction pathway. We showed that TGF-β1 stimulated the synthesis of HO-1 in a concentration- and time-dependent manner, which can be mitigated by blockade of the phospholipase (PLC)γ/protein kinase C alpha (PKC)α pathway. We also showed that the expression of miRNA-519b, which blocks HO-1 transcription, is inhibited by TGF-β1, and the suppression of miRNA 519b could be reversed via blockade of the PLCγ/PKCα pathway. Conclusions/Significance: TGF-β1 stimulated the expression of HO-1 via activating the PLCγ/PKCα pathway and suppressing the downstream expression of miRNA-519b. These results may shed light on the pathogenesis and treatment of OA. [ABSTRACT FROM AUTHOR]

Background: Clinical success of total ankle arthroplasty depends heavily on the available information on the morphology of the bones, often obtained from measurements on planar radiographs. The current study aimed to evaluate the intra-rater, inter-rater and inter-session reliability and the validity of radiograph-based measurements of ankle morphology, and to quantify the effects of examiner experience on these measurements. Methods: Twenty-four fresh frozen ankle specimens were CT scanned, data of which were used to reconstruct 3D volumetric bone models for synthesizing 2D radiographs. Two orthopaedic surgeons with different levels of clinical experience identified twenty landmarks five times on each of the synthesized sagittal and coronal radiographs and repeated the test on a subsequent day within 5 days. The landmarks were used to calculate fourteen morphological parameters. The two-way mixed-effects (ICC3,1), two-way random-effects (ICC2,k) and two-way random-effects (ICC3,k) models were used, respectively, to assess the intra-rater, inter-rater and inter-session reliability of measurements. The validity of the measurements for each examiner was assessed by comparing them with gold standard values obtained from the 2D radiographs projected from the 3D volumetric models using Pearson's correlation analysis and Bland and Altman plots, and the differences were defined as the measurement errors. Results: Most of the morphological parameters were of good to very good intra-rater, inter-session and inter-rater reliability for both examiners (ICC > 0.61). Experience appeared to affect the inter-rater and inter-session reliability, the senior examiner showing greater inter-session ICC values than the junior examiner. Most of the tibial parameters had moderate to excellent correlations with the corresponding gold standard values but were underestimated by both examiners, in contrast to most of the talar parameters that were overestimated and had only poor to fair correlations. Conclusions: Most of the morphological parameters of the ankle can be estimated from radiographs with good to very good intra-rater, inter-session and inter-rater reliability, for both clinically experienced and less experienced examiners. Clinical experience helped increase the reliability of repeated evaluations after a longer interval, such as in a follow-up assessment. It is suggested that critical clinical decisions based on repeated morphology measurements should be made by more experienced surgeons or after appropriate training. [ABSTRACT FROM AUTHOR]

Background: Robot-based joint-testing systems (RJTS) can be used to perform unconstrained laxity tests, measuring the stiffness of a degree of freedom (DOF) of the joint at a fixed flexion angle while allowing the other DOFs unconstrained movement. Previous studies using the force-position hybrid (FPH) control method proposed by Fujie et al. (J Biomech Eng 115(3):211-7, 1993) focused on anterior/posterior tests. Its convergence and applicability on other clinically relevant DOFs such as valgus/varus have not been demonstrated. The current s1tudy aimed to develop a 6-DOF RJTS using an industrial robot, to propose two new force-position hybrid control methods, and to evaluate the performance of the methods and FPH in controlling the RJTS for anterior/posterior and valgus/varus laxity tests of the knee joint.Methods: An RJTS was developed using an industrial 6-DOF robot with a 6-component load-cell attached at the effector. The performances of FPH and two new control methods, namely force-position alternate control (FPA) and force-position hybrid control with force-moment control (FPHFM), for unconstrained anterior/posterior and valgus/varus laxity tests were evaluated and compared with traditional constrained tests (CT) in terms of the number of control iterations, total time and the constraining forces and moments.Results: As opposed to CT, the other three control methods successfully reduced the constraining forces and moments for both anterior/posterior and valgus/varus tests, FPHFM being the best followed in order by FPA and FPH. FPHFM had root-mean-squared constraining forces and moments of less than 2.2 N and 0.09 Nm, respectively at 0° flexion, and 2.3 N and 0.14 Nm at 30° flexion. The corresponding values for FPH were 8.5 N and 0.33 Nm, and 11.5 N and 0.45 Nm, respectively. Given the same control parameters including the compliance matrix, FPHFM and FPA reduced the constraining loads of FPH at the expense of additional control iterations, and thus increased total time, FPA taking about 10 % longer than FPHFM.Conclusions: The FPHFM would be the best choice among the methods considered when longer total time is acceptable in the intended clinical applications. The current results will be useful for selecting a force-position hybrid control method for unconstrained laxity tests using an RJTS. [ABSTRACT FROM AUTHOR]

Functional performance of total knee replacement (TKR) is often assessed using skin marker-based stereophotogrammetry, which can be affected by soft tissue artifacts (STA). The current study aimed to compare the STA and their effects on the kinematics of the knee between twelve patients with TKR and twelve healthy controls during sit-to-stand, and to assess the effects of STA on the statistical between-group comparisons. Each subject performed the sit-to-stand task while motions of the skin markers and the knees were measured by a motion capture system integrated with a three-dimensional fluoroscopy technique. The bone motions measured by the three-dimensional fluoroscopy were taken as the gold standard, with respect to which the STA of the markers were obtained. The STA were found to affect the calculated segmental poses and knee kinematics between the groups differently. The STA resulted in artefactual posterior displacements of the knee joint center, with magnitudes significantly greater in TKR than controls (p<0.01). The STA-induced knee external rotations in TKR were smaller than those in controls with mean differences of 2.3-3.0°. These between-group differences in the STA effects on knee kinematics in turn concealed the true between-group differences in the anterior-posterior translation and internal/external rotation of knee while leading to false significant between-group differences in the abduction/adduction and proximal-distal translation. [ABSTRACT FROM AUTHOR]

Background: Although various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached. Glucosamine (GlcN) is widely used as a nutritional supplement. However, the clinical- evidence-based outcome of GlcN administration remains controversial. N-acetyl-D-glucosamine (GlcNAc), a derivative of GlcN, shows chondroprotective activity and mediates the activation of articular chondrocytes. Therefore, we investigated the effect of intra-articular administration of GlcNAc in rabbits' knee joints with experimental full-thickness articular cartilage (FTAC) defects.Methods: Twelve male adult New Zealand white rabbits, providing 24 knees, were used in this study. FTAC defects were created in the high-weight-bearing area of the medial femoral condyles of bilateral knees. All rabbits were randomly allocated to analysis at postsurgical week 4 or postsurgical week 12. In the week 4 group, rabbits' knees (six per group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 3 weeks, beginning 1 week postoperatively. In the week 12 group, the rabbits' knees (six in each group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 4 weeks, beginning 1 week postoperatively. Rabbits were sacrificed at 4 or 12 weeks after surgery for macroscopic, histological and radiological examinations of the knee joints.Results: All rabbits had no systemic or local adverse effects. The saline and GlcNAc groups showed visible differences in healing of the FTAC defect at the end of testing. At week 4, the GlcNAc group had a higher level of collagen type II (COL II) and showed up-regulated production of transforming growth factor (TGF)-β2 and TGF-β3, suggesting the involvement of endogenous growth factors. At week 12, the GlcNAc group displayed formation of hyaline-like cartilage regeneration with mature chondrocytes (SOX9+), robust glycosaminoglycan (GAG) content, and positive COL II content in both the adjacent cartilage and reparative sites. However, the saline group demonstrated mainly fibrocartilage scar tissue, indicating COL I expression. Furthermore, the GlcNAc group had significantly higher bone volume per tissue volume and higher trabecular thickness than the saline group.Conclusions: Intra-articular GlcNAc may promote the repair of experimental FTAC defects in the rabbit knee joint model. [ABSTRACT FROM AUTHOR]

Background context Absence or inadequate filling of cement in the fractured vertebrae can cause unsatisfactory results in a vertebroplasty. Repeated needle insertion can reduce the incidence of recollapse at the cemented vertebrae. However, when inserting the second needle in the usual method, it takes the same time and radiation exposure as the first needle. Purpose To report a Kirschner wire-guided technique for inserting a second needle into inadequately filled vertebrae in vertebroplasty that can make the procedure simple, effective, and, most importantly, reduce the radiation exposure. Study design Description of a modified surgical technique with retrospective data analysis. Patient sample From January 2012 to December 2012, 87 percutaneous vertebroplasties were performed in our department to treat painful osteoporotic compression fractures. Seven adult patients (five women, two men; mean age: 75.7 years) had inadequate cement filling in the treated vertebrae that required the insertion of a second needle. Outcome measures Back pain was measured using the visual analog scale (VAS). The post-vertebroplasty anterior vertebral height and local kyphotic angle were used as the radiologic parameters. Intraoperative procedure time and fluoroscopy shots and postoperative complication were also evaluated. Methods The stylus of the first needle was inserted into the trocar to push the cement out of the trocar. The stylus was removed, a small diameter K-wire was inserted into the trocar, and the trocar was then removed. A second (new) trocar was inserted into the vertebral body following the track of the K-wire. When the new trocar reached the posterior 1/4 of the vertebral body, the K-wire was removed, the stylus was inserted, and the new needle was advanced to the anterior third of the vertebra. Cement was then injected into the new area until the filling was adequate. Results The immediate post-vertebroplasty anterior vertebral height was 23.31±1.95 mm, changed to 22.20±3.72 mm at final follow-up. The VAS decreased from a mean of 8.4 before vertebroplasty to 1.6 at the final follow-up. The follow-up duration ranged from 6 to 15 months (mean 12.6 months). There was no case of recollapse of the cemented vertebrae and no procedure-related complications. The procedure time of historical controls was 153.5 seconds, which reduced to 47.9 seconds by using this technique. The fluoroscopy shots of historical controls were 9.7 shots, which reduced to 2 shots by using this technique. Conclusions This report suggests that Kirschner wire-guided technique for inserting a second needle during vertebroplasty could make the procedure simple, effective, and, most importantly, reduce the procedure time and radiation exposure. [ABSTRACT FROM AUTHOR]

Osteochondral lesions in weight-bearing joints often fail to heal due to their poor intrinsic repair capacity and may lead to severe complications such as osteoarthritis. This study investigated the chondrogenesis, osteogenesis, and regenerative potential of an injectable, thermoresponsive chitosan-graft-poly(N-isopropylacrylamide) (CS-g–PNIPAAm, or CSPN) hydrogel combined with infrapatellar fat pad-derived mesenchymal stem cell (IFPSC) and platelet-rich plasma (PRP) with regard to osteochondral regeneration. CSPN hydrogels were prepared and characterized using several procedures. Optimal CSPN hydrogel (CSPN hydrogel with 67% of PNIPAAm, or CSPN05) was examined following a biochemical assay and animal implantation. PRP incorporated CSPN05 hydrogel, CSPN05-PRP, was fabricated. We found that rabbit IFPSCs (rIFPSCs) cultured in the CSPN05-PRP hydrogel (rIFPSC–CSPN05–PRP) enhanced the expression of chondrogenic and osteogenic genes after 1, 3, 5, and 7 days of culture and significantly increased sulfated glycosaminoglycan content, alkaline phosphatase activity, and mineralization after 5 and 7 days of culture compared with PN and CSPN05. In addition, PRP induced the expression of specific signaling molecules for chondrogenesis and osteogenesis in its signaling pathway. A preliminary in vivo study showed that rIFPSC-CSPN05–PRP could effectively regenerate the osteochondral defect at 4 weeks. Thus, the combination of IFPSC, the CSPN hydrogel, and PRP can synergistically enhance chondrogenic and osteogenic gene expression, cartilage- and bone-specific extracellular matrix production, hyaline cartilage regeneration, and mineralized osseous tissue formation. CSPN scaffolds with PRP show potential as biomaterial by providing mechanical support for cell growth and inducing stem cells to differentiate into osteochondral lineages for application in regenerative medicine. [Display omitted] [ABSTRACT FROM AUTHOR]

Background/Objective: Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved. Methodology/Principal Findings: In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses. Treatment with nicardipine inhibited microglial cell migration. Nicardipine also significantly inhibited LPS plus IFN-γ-induced release of nitric oxide (NO), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, nicardipine also inhibited microglial activation by peptidoglycan, the major component of the Gram-positive bacterium cell wall. Notably, nicardipine also showed significant anti-neuroinflammatory effects on microglial activation in mice in vivo. Conclusion/Significance: The present study is the first to report a novel inhibitory role of nicardipine on neuroinflammation and provides a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Long-term alendronate therapy may lead to atypical femoral fractures in a very few patients. However, the management protocol to optimize fracture healing remains undetermined. The purpose of this study was to describe the time to union of atypical femoral fractures after surgical nailing in patients on long-term alendronate therapy, with continuation of alendronate or discontinuation of alendronate, and administration of bone-forming agents. Findings: From January 2004 to December 2011, the records of patients at our institution on long-term alendronate therapy for more than 36 months and sustaining atypical femoral fractures that had undergone surgical nailing, with continuation of alendronate or discontinuation of alendronate and administration of bone-forming agents were reviewed. During the 8-year study period, we treated 10 atypical femoral fractures with surgical nailing in 7 consecutive osteopenic or osteoporotic patients on long-term alendronate therapy for more than 36 months. There were no post-operative complications or needs for revision surgery. All fractures achieved union during follow-up. Mean union time was 23.5 months (range, 18-31 months) for 6 fractures with continuation of alendronate after surgery, and 4.5 months (range, 4-5 months) for 4 fractures with discontinuation of alendronate and administration of bone-forming agents after surgery. Conclusions: Discontinuation of alendronate and administration of bone-forming agents after surgical nailing may promote union of atypical femoral fractures in patients on long-term alendronate therapy. [ABSTRACT FROM AUTHOR]

Resistin is originally reported as an adipose tissue-specific hormone and is thought to represent a link between obesity and insulin-resistant diabetes. Adipokines exert energy-regulation and has been reported to have neuroprotective effect like leptin, adiponectin, and ghrelin. However, the role of resistin in neuroprotective effect has not been explored. 6-hydroxydopamine (6-OHDA), one of the most investigated Parkinson's disease neurotoxins, is widely used to study mechanisms of cell death in dopaminergic neurons. In the present study, our results show that treatment of resistin protects 6-OHDA-induced cell death in dopaminergic-like MES23.5 cells. Resistin also antagonizes 6-OHDA-induced apoptotic cell death measured by fluorescence-activated cell sorter (FACS) analysis and Hochest 33342 staining. Furthermore, treatment of resistin also dramatically reduces 6-OHDA-mediated ROS production and mitochondria transmembrane potential dissipation. Moreover, expression of 6-OHDA-induced apoptotic markers, such as Bcl-2 degradation, Bax expression, PARP degradation and caspase 3 activity increase, are all attenuated by resistin treatment. Our results also show that resistin induces up-regulation of heat shock protein (Hsp) 32 (heme oxygenase-1, HO-1) and Hsc (heat shock cognate) 70. The protective effect of resistin on 6-OHDA-induced cell death is abolished by HO-1 inhibitor zinc protoporphyrin IX and HSP inhibitor KNK437. These results suggest the neuroprotective effects of resistin against 6-OHDA-induced cell death with the underlying mechanisms of inhibiting oxidative stress and apoptosis. Therefore, we suggest that resistin may provide a useful therapeutic strategy for neurodegenerative diseases such as Parkinson's disease. J. Cell. Physiol. 228: 563-571, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Background: Diabetes is an independent risk factor of osteoarthritis (OA). Angiogenesis is essential for the progression of OA. Here, we investigated the intracellular signaling pathways involved in high glucose (HG)-induced vascular endothelial growth factor (VEGF) expression in human synovial fibroblast cells. Methods: HG-mediated VEGF expression was assessed with qPCR and ELISA. The mechanisms of action of HG in different signaling pathways were studied using Western blotting. Knockdown of proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the VEGF promoter. Results: Stimulation of OA synovial fibroblasts (OASF) with HG induced concentration- and time-dependent increases in VEGF expression. Treatment of OASF with HG increased reactive oxygen species (ROS) generation. Pretreatment with NADPH oxidase inhibitor (APO or DPI), ROS scavenger (NAC), PI3K inhibitor (Ly294002 or wortmannin), Akt inhibitor, or AP-1 inhibitor (curcumin or tanshinone IIA) blocked the HG-induced VEGF production. HG also increased PI3K and Akt activation. Treatment of OASF with HG increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the VEGF promoter. Conclusions: Our results suggest that the HG increases VEGF expression in human synovial fibroblasts via the ROS, PI3K, Akt, c-Jun and AP-1 signaling pathway. General significance: We link high glucose on VEGF expression in osteoarthritis. [Copyright &y& Elsevier]

Objective Thrombin is a key factor involved in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA). The aim of this study was to investigate the intracellular signaling pathways involved in thrombin-induced CCL2 expression in human osteoblasts. Methods Thrombin-mediated CCL2 expression was assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The mechanisms of action of thrombin in different signaling pathways were studied using Western blotting. Knockdown of protease-activated receptor (PAR) protein was achieved by small interfering RNA (siRNA) transfection. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the CCL2 promoter. Transient transfection was used to examine activator protein 1 (AP-1) activity. Results Stimulation of human primary osteoblasts and MG-63 cells with thrombin induced CCL2 expression. PAR-1-specific siRNA (but not other PAR siRNA) was involved in thrombin-mediated up-regulation of CCL2. Thrombin-mediated CCL2 production was attenuated by the thrombin inhibitor PPACK, the protein kinase Cδ (PKCδ) inhibitor rottlerin, the c-Src inhibitor PP2, epidermal growth factor receptor (EGFR) inhibitor AG-1478, MEK inhibitors PD98059 and U0126, or AP-1 inhibitors curcumin and tanshinone IIA. Stimulation of cells with thrombin increased PKCδ, c-Src, EGFR, MEK, and ERK activation. Treatment of osteoblasts with thrombin also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the CCL2 promoter. Conclusion Our results suggest that the interaction between thrombin and PAR-1 increases CCL2 expression in human osteoblasts via the PKCδ/c-Src/ EGFR transactivation/MEK/ERK/c-Jun/AP-1 pathway. [ABSTRACT FROM AUTHOR]

The nephroblastoma overexpressed (NOV) gene, also called CCN3, regulates differentiation of skeletal mesenchymal cells. Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and bone formation, but the effects of CCN3 on BMP expression and bone formation in cultured osteoblasts are largely unknown. Here we found that CCN3 increased BMP-4 expression and bone nodule formation in cultured osteoblast. Monoclonal antibodies for α5β1 and αvβ5 integrins, and inhibitors of integrin-linked kinase (ILK), p38, and JNK, all inhibited CCN3-induced bone nodule formation and BMP-4 up-regulation of osteoblasts. CCN3 stimulation increased the kinase activity of ILK and phosphorylation of p38 and JNK. Inhibitors of activator protein-1 (AP-1) also suppressed bone nodule formation and BMP-4 expression enhanced by CCN3. Moreover, CCN3-induced c-Jun translocation into the nucleus, and the binding of c-Jun to the AP-1 element on the BMP-4 promoter were both inhibited by specific inhibitors of the ILK, p38, and JNK cascades. Taken together, our results provide evidence that CCN3 enhances BMP-4 expression and bone nodule formation in osteoblasts, and that the integrin receptor, ILK, p38, JNK, and AP-1 signaling pathways may be involved. J. Cell. Physiol. 227: 2531-2541, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Patients with un-relieved pain after vertebroplasty due to re-collapse of the cemented vertebrae have been reported. Here we report a technique of vertebroplasty that can reduce the incidence of re-collapse at the cemented vertebrae. Materials and methods: Between March 2002 and September 2008, 134 patients with 205 painful vertebral compression fractures underwent vertebroplasty in our institutes. The indication of using this technique was unfilled area more than 25% of the vertebral body height in lateral radiograph. The vertebroplasty procedure was performed according to the technique described by Jensen. If the unfilled area were more than 25% of the vertebral body height in lateral radiograph, another needle would be inserted aiming at the unfilled area. As outcome measurement, a visual analog scale with 10 divisions and plain radiographs (to measure the anterior vertebral body height of cemented vertebrae) were used. Results: Thirteen vertebrae were treated with this technique. The mean age was 74.4years. The immediate post-vertebroplasty anterior vertebral height was 24.92±3.59mm, changed to 23.52±3.54mm at final follow-up. The visual analog scale decreased from a mean of 8.7 before vertebroplasty to 2.3 at final follow-up. The follow-up duration ranged from 15 to 38 months (mean 18.5 months). There was no case of re-collapse of the cemented vertebrae, and no procedure-related complications. Conclusion: In the treatment of vertebral compression fractures by percutaneous vertebroplasty, repeat needle insertion to the unfilled area may be helpful to decrease the incidence of re-collapse of cemented vertebrae if the unfilled area is more than 25% of the vertebral body height in lateral radiograph. [Copyright &y& Elsevier]

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN3, also called nephroblastoma overexpressed gene (NOV), regulates proliferation and differentiation of cancer cells. However, the effect of CCN3 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). αvβ3 or αvβ5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase (PI3K) inhibitors (Ly294002 and wortmannin) and Akt inhibitor inhibited the CCN3-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. CCN3 stimulation increased the phosphorylation of focal adhesion kinase (FAK), PI3K, and Akt. In addition, NF-κB inhibitors also suppressed the cell migration and MMP-13 expression enhanced by CCN3. Moreover, CCN3 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-13 promoter. Taken together, our results indicate that CCN3 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the αvβ3/αvβ5 integrin receptor, FAK, PI3K, Akt, p65, and NF-κB signal transduction pathway. J. Cell. Physiol. 226: 3181-3189, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Osteosarcoma is characterized by a high malignant and metastatic potential. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin synthase, has been implicated in tumor metastasis. Nephroblastoma overexpressed gene (NOV), also called CCN3, was regulated proliferation and differentiation of cancer cells. However, the effect of NOV on migration activity and COX-2 expression in human osteosarcoma cells is mostly unknown. Here we found that NOV increased the migration and expression of COX-2 in human osteosarcoma cells. αvβ5 monoclonal antibody (mAb), integrin-linked kinase (ILK) and Akt inhibitor reduced the NOV-enhanced the migration and COX-2 up-regulation of osteosarcoma cells. NOV stimulation increased the ILK kinase activity and phosphorylation of Akt. In addition, c-Jun siRNA also antagonized the NOV-mediated migration and COX-2 expression. Moreover, NOV enhanced the AP-1 binding activity and promoter activity. Taken together, these results suggest that the NOV acts through αvβ5 integrin to activate ILK and Akt, which in turn activates c-Jun and AP-1, resulting in the activations of COX-2 and contributing the migration of human osteosarcoma cells. [Copyright &y& Elsevier]

Abstract: The current study aimed to quantify the soft tissue artifacts of selected markers on the thigh and shank, and their effects on the calculated joint center translations, angles and moments of the knee during sit-to-stand. Ten patients with total knee replacements rose from a chair under simultaneous surveillance of a motion capture system, a force-plate and a fluoroscopy system. The “true” poses of the thigh and shank were defined by those of the femoral and tibial components obtained using a three-dimensional fluoroscopy method. The soft tissue artifacts of the skin markers were calculated as their movement relative to the underlying prosthesis components. The joint center translations, angles and moments at the knee were also calculated separately using skin markers and the registered prosthesis poses. Considerable soft tissue artifacts were found, leading to significantly underestimated flexion and internal rotation angles, and extensor moments, but overestimated joint center translations and adduction. The current study provides accurate data of the kinematics and kinetics of total knee replacements during sit-to-stand. The effects of soft tissue artifacts on the calculated joint center translations, angles and moments were also quantified for the first time in the literature. The results may help in developing guidelines for using skin markers and in establishing databases in the biomechanical assessment of sit-to-stand in patients with total knee replacements. [Copyright &y& Elsevier]

Female athletes are more likely to sustain an anterior cruciate ligament (ACL) injury. Knee laxity, hyperextension and limb dominance have been suggested as possible factors contributing to the knee injury. The aims of this study were to investigate the physiological anterior knee laxity between the dominant and non-dominant limb and in healthy young females with and without hyperextension knees. Forty-two healthy young females, 21 with hyperextension knees, were recruited voluntarily for this study. The subjects were tested with KT-2000 knee ligament arthrometer at both knees with flexion 30 degrees to obtain the anterior tibial displacements at loadings of 45, 67, 89 and 134 N. The initial and terminal stiffnesses were further calculated and analyzed to demonstrate the differences in the characteristics of knee laxity between limbs and groups. The results showed that there was no significant displacement difference between hyperextension and non-hyperextension groups. However, different physiological anterior laxities were illustrated for the different limbs and groups. The non-dominant side of the hyperextension group had significantly smaller terminal stiffness than that of the non-hyperextension group. The dominant side of the hyperextension group had larger laxity than the non-dominant side in the higher loading conditions. These findings may explain hyperextension knees are at greater risk of sustaining an ACL injury. [ABSTRACT FROM AUTHOR]

We retrospectively analysed 106 consecutive traumatic humeral shaft fractures over a five-year period. The mechanism of injury, age, gender, fracture types, associated injury and the presence of injury to the radial nerve were reviewed. The incidence was about 10 per 100,000 per year; most were closed fractures in young males which had been sustained as a result of traffic accidents. The age-gender distribution was characterised by gradually increased incidence from the fifth decade in women, while it reached a peak at the third decade and decreased after the fifth decade in men. The results revealed different epidemiological features from previous studies. The epidemiology differs between ethnicity and country, and updating the epidemiological features of humeral shaft fractures may provide information for appropriate treatment programmes. This study documents the epidemiology of humeral shaft fracture in Taiwan, probably for the first time in this Asian community. [ABSTRACT FROM AUTHOR]

Abstract: CCL5 (previously called RANTES) is in the CC-chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. Besides, integrins are the major adhesive molecules in mammalian cells. Here we found CCL5 increased the migration and cell surface expression of αvβ3 integrin in human lung cancer cells (A549 cells). CCL5 stimulation increased phosphorylation of the p85α subunit of phosphatidylinositol 3-kinase (PI3K) and serine 473 of Akt. Also, we found that PI3K inhibitor (Ly294002) or Akt inhibitor suppressed CCL5-induced migration activities and integrin expression of A549 cells. Transfection of cells with p85 or Akt mutant also reduced CCL5-mediated cancer migration. In addition, treatment of A549 cells with CCL5 induced IκB kinase α/β (IKK α/β) phosphorylation, IκB phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity. Furthermore, the CCL5-mediated increases in p65 Ser536 phosphorylation were inhibited by Ly294002 and Akt inhibitor. Taken together, our results suggest that CCL5 acts through PI3K/Akt, which in turn activates IKKα/β and NF-κB, resulting in the activation of αvβ3 integrin and contributing to the migration of human lung cancer cells. [Copyright &y& Elsevier]

Abstract: Measurement of the changes of the three-dimensional (3D) motion and surface kinematics of the knee under different external loading conditions is essential for the understanding and evaluation of the function of the joint, as well as for relevant clinical applications. Knee extension exercise (KEE) has been applied extensively in the rehabilitation programs of patients with various knee disorders. This study measured the 3D knee kinematics of eight normal subjects during active knee extension for unloaded and loaded conditions using a voxel-based method for the registration of fluoroscopic images with CT bone data. The knee kinematics during unloaded conditions were found to be similar to previous findings. A mass of 5kg at the ankle did not affect the joint angles but significantly altered the lateral contact positions during knee extension, especially at knee flexion angles higher than 75°, and also reduced the asymmetry of the surface kinematics between the medial and lateral condyles. The results of the current study may be useful for knee replacement design and for developing guidelines for the use of KEEs for the rehabilitation of patients with knee disorders. [Copyright &y& Elsevier]

Abstract: Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA) in synovial tissues. We investigated the signaling pathway involved in IL-6 production caused by thrombin in synovial fibroblasts. Thrombin caused concentration- and time-dependent increases in IL-6 production. By using pharmacological inhibitors or activators or genetic inhibition by the protease activated receptor (PAR), siRNA revealed that the PAR1 receptor but not other PAR receptors is involved in thrombin-mediated up-regulation of IL-6. Thrombin-mediated IL-6 production was attenuated by thrombin inhibitor (PPACK), phospholipase C inhibitor (U73122), protein kinase Cα inhibitor (Ro320432), Src inhibitor (PP2), NF-κB inhibitor (PDTC), IκB protease inhibitor (TPCK), or NF-κB inhibitor peptide. Stimulation of synovial fibroblasts with thrombin activated IκB kinase α/β (IKK α/β), IκBα phosphorylation, IκBα degradation, p65 phosphorylation at Ser276, p65 and p50 translocation from the cytosol to the nucleus, and κB-luciferase activity. Thrombin-mediated an increase of IKK α/β activity, κB-luciferase activity and p65 and p50 binding to the NF-κB element was inhibited by PPACK, U73122, Ro320432 and PP2. The binding of p65 and p50 to the NF-κB elements, as well as the recruitment of p300 and the enhancement of p50 acetylation on the IL-6 promoter was enhanced by thrombin. Our results suggest that thrombin increased IL-6 production in synovial fibroblasts via the PAR1 receptor/PI-PLC/PKCα/c-Src/NF-κB and p300 signaling pathway. [Copyright &y& Elsevier]

2-Methoxyestradiol (2ME) is an endogenous metabolite with estrogen receptor-independent anti-tumor activity. The current study seeks to determine the mechanism of anti-tumor activity of 2ME on human chondrosarcoma. 2ME caused a time- and dose-dependent cytotoxity in chondrosarcoma cells, while primary chondrocytes were minimally affected. Cells accumulated in G0/G1 phase in response to 2ME and DAPI stain indicated an induction of apoptosis. Bax, Cytochrome C, and Caspase-3 protein expression were increased, while p53 expression was decreased. A higher Bax/Bcl-2 ratio followed 2ME treatment. 2ME has a potentially promising role as a systemic therapy of chondrosarcoma when the mechanism of action is better delineated. Published by Wiley Periodicals, Inc. J Orthop Res 25:1106-1114, 2007 [ABSTRACT FROM AUTHOR]

Female athletes are two to eight times more likely to suffer a knee or ankle ligament injury than male athletes, and sex hormones have been considered to play an important role in the injury. Because ligaments are always under mechanical loading during sports, mechanical force is also a critical factor in ligament injuries. In this study, the effects of estrogen and mechanical loading on the gene expression of three major components of ligament—collagen type I, type III, and biglycan—in primary cultured porcine anterior cruciate ligament (ACL) fibroblasts were investigated individually and collectively using reverse transcript-polymerase chain reaction (RT-PCR). The results revealed that cyclic tensile loading alone increased the messenger RNA expression of collagen I but did not affect that of collagen III and biglycan, and estrogen alone increased the gene expression of collagen I and III but not of biglycan. However, combined administration of estrogen and cyclic loading inhibited the mRNA expression of all the three genes. These results suggested that the inhibition of the gene expression of major extracellular matrix component molecules caused by the combined effects of estrogen and mechanical loading, unique to females, might be responsible for the increased incidence of ligaments injury in female athletes. [Copyright &y& Elsevier]

The purpose of this study was to examine whether mechanical tensile forces affect estrogen regulation of collagen synthesis of anterior cruciate ligament fibroblasts at the mRNA level. Estrogen was studied at three physiologic levels, 10−11, 10−10, and 10−9 M. The results revealed that estrogen alone stimulated Type I and III collagen synthesis at the mRNA level, and application of mechanical force decreased the expression of collagen Type I and III genes at all tested estrogen levels. These findings suggest that estrogen may directly regulate ligament structure and function by alteration of Type I and III collagen synthesis. This regulation is dependent on mechanical loading. [Copyright &y& Elsevier]