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There are various techniques used for tendon lengthening, of which Z-lengthening and sliding-lengthening are the most frequently performed. In patients with cerebral palsy, tendon lengthening may often be necessary at multiple sites. However, they can cause various complications, such as inaccurate extension, overextension, and a lack of tendon continuity. We modified the sliding-lengthening technique with a locking mechanism to address these issues. This technical note aims to describe the surgical technique and pitfalls associated with the modified sliding-lengthening approach and suture locking mechanism. The tendon was exposed and stabilized using sterilized spitz tubes and was then threaded so that each loop length was equivalent to the amount of tendon extension. Symmetrical hemisection of both ends of the tendon was performed, and the tendon was carefully extended to create a tense loop. The modified sliding-lengthening technique with the locking suture mechanism may be an advantageous method that accurately addresses extension volume, prevents hyperextension, and maintains tendon continuity, even when smaller incisions are used.

Ken Takata, Kentaro Uchida, Shotaro Takano, Manabu Mukai, Gen Inoue, Hiroyuki Sekiguchi, Jun Aikawa, Masayuki Miyagi, Dai Iwase, Masashi Takaso Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, JapanCorrespondence: Kentaro UchidaDepartment of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-Ku Kitasato, Sagamihara City, Kanagawa, 252-0374, JapanTel/Fax +81-042-778-9217Email kuchida@med.kitasato-u.ac.jpPurpose: Obesity is associated with the risk of developing knee osteoarthritis (KOA). Furthermore, synovial basic fibroblast growth factor (bFGF) is linked to the severity of KOA. We previously demonstrated that bFGF and mast cell (MC) marker expression were elevated in the synovial tissues (ST) of KOA patients with obesity. However, it remains unclear whether MCs contribute to bFGF expression and regulation.Patients and Methods: Radiographically diagnosed KOA patients (n=249) were assigned to groups based on the body mass index (BMI) classifications used by the World Health Organization: normal-weight (NW, BMI < 25 kg/m2, n=95), overweight (OW, BMI ≥ 25 and < 30, n=109) and obese (OB, ≥ 30 kg/m2, n=45). BFGF expression in the ST was examined using quantitative polymerase chain reaction and compared across the BMI groups. Additionally, BFGF and interleukin (IL) 13 expression were examined in freshly extracted MC-rich (THY-1-, CD3-, CD14-, and CD19-) and MC-poor (THY-1+, CD3+, CD14+, or CD19+) fractions from ST. Moreover, regulation of BFGF expression by IL-13 was studied in CD14-negative (fibroblast-rich) and CD14-positive (M&phis;-rich) and cells in culture.Results: BFGF expression was significantly higher in OB than in NW patients. Furthermore, although IL13 was significantly higher in the MC-rich than the MC-poor fraction, BFGF expression was comparable. Recombinant human IL-13 stimulated expression of BFGF in synovial fibroblast cells.Conclusion: BFGF expression is higher in the ST of KOA patients with obesity. Increased numbers of MCs may contribute to the elevated BFGF expression through IL-13 in KOA patients with obesity.Keywords: obesity, mast cell, osteoarthritis, BFGF, IL13, synovial tissues

Obesity is a risk factor for knee osteoarthritis (KOA). Neuromedin U (NMU) and NMU receptors (NMUR1 and NMUR2) are associated with obesity-related disorders and found in mast cells (MCs), which are elevated in osteoarthritis. However, NMU/NMUR expression was not examined in the synovial membrane (SM) or synovial MCs of obese osteoarthritis patients. We compared expression of NMU, NMUR1, NMUR2, and the mast cell (MC) marker, CPA3, in the SM of KOA patients categorized as normal weight (NW; BMI < 25 kg/m2, n = 79), overweight (OW; BMI ≥ 25 and

Purpose The mechanisms governing evidence that obesity is a risk factor for osteoarthritis (OA) are not well understood. We previously reported an increase in mast cell (MC) marker expression in the osteoarthritic synovial membrane (SM) of patients with obesity. We hypothesized that an enzyme produced by MC, β-tryptase, may be increased in the SM of obese patients with knee OA and contribute to synovial inflammation. This study investigated the expression of the β-tryptase encoding gene, TPSB2, in the SM of obese patients with knee OA and β-tryptase-mediated regulation of IL-1β in synovial cells. Patients and Methods A total of 216 patients radiographically diagnosed with knee OA were grouped according to the World Health Organization's body mass index classifications: normal weight (NW

Background. Previous studies suggest the presence of an association of vascular endothelial growth factor (VEGF) with osteoarthritis (OA) severity and pain in patients with knee OA. VEGF expression in human synovial fibroblasts (SFs) is induced by transforming growth factor-beta (TGFβ). However, the signaling pathway governing TGFβ-mediated regulation of VEGF in SFs has not been identified. Methods. OA patients who underwent total knee arthroplasty had their synovial tissue (SYT) extracted and the constituent SFs cultured. The cells were stimulated with culture medium (control), human recombinant TGFβ (hrTGFβ), hrTGFβ + ALK5 inhibitor SB505124, hrTGFβ + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or hrTGFβ + p38 inhibitor SB203580 for 6 h. VEGF mRNA expression in SFs was examined using real-time polymerase chain reaction and VEGF protein production in the cell supernatant was examined using enzyme-linked immunosorbent assay. Additionally, phosphorylated levels of SMAD2 and p38 were examined using western blotting. Results. ALK5 (SB505124) and TAK1 (5Z-oxozeaenol) inhibitors completely suppressed TGFβ-induced VEGF mRNA expression and VEGF protein production. Both SB505124 and 5Z-oxozeaenol also suppressed SMAD2 and p38 phosphorylation. The p38 inhibitor (SB203580) partially inhibited TGFβ-mediated VEGF mRNA and VEGF protein production. Conclusion. TGFβ-mediated regulation of VEGF expression and VEGF protein production in the SYT of OA patients occurs through both the canonical and noncanonical pathway.

Purpose: While research suggests that obesity is a risk factor for knee osteoarthritis (KOA), the mechanisms are not fully understood. Mast cell (MC) numbers are increased in the osteoarthritic synovium and in the adipose tissue of obese individuals. We hypothesized that MC numbers are increased in the synovium of obese KOA patients. This study investigated MC marker and MC-generated cytokine/growth factor expression in the synovium of obese KOA patients. Patients and methods: Patients radiographically diagnosed with KOA (male: 38, female: 132) were allocated to three groups based on their body mass index (BMI): normal (

Whether femoral varus derotational osteotomy (VDRO) alone or a combination of femoral and pelvic osteotomies should be performed for hip dislocation in nonambulatory children with cerebral palsy (CP) remains controversial. Few studies have reported radiographical results after the surgical treatment in nonambulatory children with CP. This study aimed to assess the results and determine predictors indicating progressive hip subluxation and redislocation after VDRO without pelvic osteotomy. We retrospectively analyzed 22 hips in 15 nonambulatory children with CP. All patients underwent VDRO without pelvic osteotomy and were followed up for at least 5 years. The mean follow-up period was 7.3 ± 1.9 years. In radiological assessments, we investigated migration percentage (MP), center-edge angle, neck-shaft angle, teardrop distance, break in Shenton's line (SL), sharp's angle, acetabular ridge angle (ARA), and the change ratio of MP (Change MP). We classified patients with an MP of

Background There are many reports of Achilles tendon lengthening procedures for equinus deformity of the ankle. We previously modified an Achilles tendon lengthening to prevent overextension with a locking mechanism suture before performing a sliding lengthening. The purpose of this study was to compare the biomechanical properties of the locking mechanism suture with sliding lengthening (L-SL) and Z-lengthening (ZL) using a rabbit model. Methods Thirty-six male Japanese white rabbits were assigned to two groups - half undergoing the L-SL technique and half undergoing the ZL technique on the flexor hallucis longus (FHL) tendon. Six rabbits in each group were sacrificed at one week, three weeks, and six weeks postoperatively and evaluated, while five rabbits underwent radiographical and biomechanical evaluation and one underwent histological evaluation. Results In extension length, L-SL was significantly lower than ZL one week postoperatively. In the L-SL group, elongation one week postoperatively was significantly lower than that three and six weeks postoperatively. In the ultimate failure load, L-SL was significantly higher than ZL one and three weeks after lengthening. In the L-SL group, the ultimate failure load one week postoperatively was significantly lower than that three and six weeks postoperatively. In the ZL group, there were significant differences at all time points. Conclusion L-SL had higher mechanical property in vivo.

Introduction The coronavirus disease 2019 (COVID-19) epidemic beginning December 2019 in China has now become a worldwide pandemic. With the need to develop an approach to manage orthopaedic surgeries, we aimed to evaluate the most current data on all the surgical cases in our department including the results of the reverse-transcriptase polymerase chain reaction (RT-PCR) assay for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods The monthly number of surgical cases from 2016 were reviewed, and compared the numbers of surgical cases both in elective and emergency surgery during the pandemic with the pre-pandemic period. The results of RT-PCR for SARS-CoV-2 in 94 orthopaedic surgery cases from May 13 to June 30, 2020, and clinical signs/symptoms, and laboratory data of 48 consecutive cases within a month from May 13 were also evaluated. Results The mean monthly number of surgeries from January to May 2020 was significantly lower than the mean number in 2019 (73.8 vs 121.9, respectively, p=0.01). The proportion of emergency surgeries in all surgeries performed in May 2020 was 35.5%, which is significantly more than the mean rate of 20.4% in 2019 (p=0.04). Hip arthroplasties and spine surgeries showed the greatest reduction, at greater than 80% and 65%, respectively. Although none of the 94 patients were positive for SARS-CoV-2, 66.7% showed signs/symptoms typical of COVID-19. The most frequent signs/symptoms were production of nasal mucus (25.5%), followed by dry cough (19.1%); and fatigue, headache, and dizziness (17.0% each). The incidence of abnormal values, which are commonly noted in COVID-19 patients, were eosinopaenia 37.5%; lymphopaenia 18.8%; thrombocytopaenia 8.3%; and elevated prothrombin time 10.4%. Conclusions Our results show that our RT-PCR negative patients showed signs/symptoms and abnormal laboratory values typical of COVID-19, indicating surgeons should be aware of these abnormalities in patients and the need to rule out COVID-19 before proceeding with surgery.

Upregulation of inflammatory cytokines and various growth factors is a significant contributor to discogenic low back pain. The aim of this study was to investigate possible regulation of pain-related molecules by macrophages and the role of macrophage-derived molecules in injured intervertebral disc (IVD)s. C57BL/6J mice were used in this study. We characterized the expression profiles of genes for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) in both intact and injured IVDs. We examined whether macrophage depletion, induced by systemic injection of clodronate-laden liposomes, affected the expression of these molecules in injured IVDs. The effect of TNF-alpha on cultured F4/80-CD11b-cells in injured IVDs was investigated. Expression of TNF-alpha and IL-1beta was significantly increased in injured IVDs, but decreased by macrophage depletion. Expression of NGF and VEGF was also significantly increased, but by contrast was not decreased by macrophage depletion. TNF-alpha treatment of F4/80-cells from injured IVDs upregulated NGF, VEGF, cyclooxygenase (COX)-2, and microsomal prostaglandin E synthase-1 (mPGES1). IVD injury upregulated inflammatory cytokines and various growth factors. Macrophages in the injured IVDs produced inflammatory cytokines, but not growth factors. Macrophage-derived inflammatory cytokines regulate growth factors and pain-related molecules. These findings demonstrate further complexity in the pathogenesis of discogenic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Kosuke Murata,1 Kentaro Uchida,1 Shotaro Takano,1 Shintaro Shoji,1 Dai Iwase,1 Gen Inoue,1 Jun Aikawa,1 Yuji Yokozeki,1 Hiroyuki Sekiguchi,2 Masashi Takaso11Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan; 2Shonan University of Medical Sciences Research Institute, Chigasaki City, Kanagawa 253-0083, JapanPurpose: While research has identified diabetes mellitus (DM) as a risk factor for knee osteoarthritis (KOA), the underlying mechanisms are not fully understood. Studies suggest that Toll-like receptor 4 (TLR4) expression is elevated in osteoarthritic lesions of OA patients and in target tissues of insulin resistance such as adipose tissue and skeletal muscle in patients with DM. TLR4 is associated with inflammation and catabolic response via regulation of matrix metalloproteases (MMPs). We hypothesized that TLR4 and MMP expression may be increased in the synovial tissue (SYN) of KOA patients with diabetic pathology. We therefore investigated TLR and MMP expression in the SYN of KOA patients with and without high haemoglobin A1c concentrations.Patients and methods: A total of 171 patients radiographically diagnosed with KOA were grouped based on their HbA1c concentration (HbA1c ≥6.5 and HbA1c

Ankle sprains are the most common lower extremity injuries associated with sports activity. Although ligament repair techniques are popular, reconstruction methods using free tendons are considered when the ligament remnant is insufficiently strong, when high-demand athletes sustain repeat ankle sprains, or in revision cases after repair. Recently, some arthroscopic reconstruction techniques have been reported. The distal fibular end is thin; therefore, surgeons must be careful while drilling the fibular tunnel. This report indicates the safe creation method of an anatomical fibular tunnel during anatomical arthroscopic reconstruction of the anterior talofibular ligament and calcaneofibular ligament. This also provides a stronger reconstruction using a 2-strand tendon graft for the anterior talofibular ligament substitute, which is thought to have less risk for postoperative graft failure.

Background The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. Methods IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. Results CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. Conclusions CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway.

Upregulation of inflammatory cytokines and various growth factors is a significant contributor to discogenic low back pain. The aim of this study was to investigate possible regulation of pain-related molecules by macrophages and the role of macrophage-derived molecules in injured intervertebral disc (IVD)s. C57BL/6J mice were used in this study. We characterized the expression profiles of genes for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) in both intact and injured IVDs. We examined whether macrophage depletion, induced by systemic injection of clodronate-laden liposomes, affected the expression of these molecules in injured IVDs. The effect of TNF-alpha on cultured F4/80-CD11b-cells in injured IVDs was investigated. Expression of TNF-alpha and IL-1beta was significantly increased in injured IVDs, but decreased by macrophage depletion. Expression of NGF and VEGF was also significantly increased, but by contrast was not decreased by macrophage depletion. TNF-alpha treatment of F4/80-cells from injured IVDs upregulated NGF, VEGF, cyclooxygenase (COX)-2, and microsomal prostaglandin E synthase-1 (mPGES1). IVD injury upregulated inflammatory cytokines and various growth factors. Macrophages in the injured IVDs produced inflammatory cytokines, but not growth factors. Macrophage-derived inflammatory cytokines regulate growth factors and pain-related molecules. These findings demonstrate further complexity in the pathogenesis of discogenic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Summary Nerve growth factor (NGF) functions to modulate osteoarthritis (OA)-associated pain. Although recent studies suggest that tumour necrosis factor (TNF)-α and interleukin (IL)-1β mediate NGF activity in human synovial fibroblasts, the regulation of NGF expression in human synovial macrophages remains unclear. Here, we examined the role of macrophages in the production and regulation of synovial (SYN) NGF in osteoarthritic knee joints by examining the mRNA expression of TNF-α and IL-1β in freshly isolated CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction) in synovial tissue from OA patients by quantitative polymerase chain reaction. We also examined the effects of IL-1β and TNF-α on NGF mRNA expression in cultured CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction). In addition, to examine the contribution of macrophages to NGF, TNF-α and IL-1β expression, we injected clodronate liposomes systemically into STR/Ort mice, an osteoarthritis animal model, to deplete macrophages. TNF-α and IL-1β mRNA levels in CD14-positive cells from the SYN of OA patients was significantly higher than that in CD14-negative cells, while NGF expression did not differ markedly between the two cell fractions. In addition, treatment of human cultured CD14-positive and -negative cells with IL-1β and TNF-α enhanced NGF mRNA and protein levels. Expression of NGF, IL-1β and TNF-α was also reduced significantly in STR/Ort mice upon macrophage depletion. These findings suggest that IL-1β and TNF-α regulate NGF expression and production in synovial macrophages and fibroblasts in osteoarthritic joints.

Shotaro Takano*, Kentaro Uchida*, Gen Inoue, Atsushi Minatani, Masayuki Miyagi, Jun Aikawa, Dai Iwase, Kenji Onuma, Manabu Mukai, Masashi Takaso Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Japan *These authors contributed equally to this work Background: Recent studies suggest that the vasodilatory neuropeptide calcitonin gene-related peptide (CGRP) is localized in the synovial tissue and may be involved in the pathology of hip and knee osteoarthritis (OA). However, the regulation and relationship between pain and CGRP expression levels in the synovial tissue of human OA patients are not fully understood.Methods: Synovial tissues were harvested from 74 participants with radiographic knee OA (unilateral Kellgren/Lawrence grades 3–4) during total knee arthroplasty. CGRP-expressing cells in the resected tissue were identified by immunohistochemical analyses. To examine CGRP expression levels, CD14-positive (CD14+) (macrophage-rich cell fraction) and CD14-negative (CD14−; fibroblast-rich cell fraction) cells were isolated from the synovial tissue. To investigate the involvement of prostaglandin E2 (PGE2) in the regulation of CGRP expression, cultured CD14− and CD14+ cells were stimulated with PGE2. In addition, CGRP expression levels in the synovial tissue of OA patients with strong/severe (visual analog scale [VAS]≥6) and mild/moderate pain (VAS

Background The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure. Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. To date, however, the expression levels of CGRP in the IPFP of human knee OA patients have not been examined. Methods IFFP and synovial (SYN) tissues were harvested from 100 individuals with radiographic knee OA (unilateral Kellgren/Lawrence [K/L] grades 2–4) during total knee arthroplasty and subjected to immunohistochemical analysis for CGRP localization. In addition, the messenger RNA (mRNA) expression levels of CGRP and cyclooxygenase-2 (COX-2) in the collected tissues were evaluated and compared using real-time PCR analysis of total RNA extracts. CGRP and COX-2 mRNA expression were also compared among individuals with K/L grades 2–4. Results CGRP-positive cells were detected in the capillaries within the IPFP and lining layer of SYN tissue. The expression levels of CGRP in the IPFP were positively correlated with COX-2 and were significantly higher than those in SYN tissue. CGRP expression in tissue from the KL4 group was twofold higher than that from the KL2 group. Conclusions The IPFP of knee OA patients produces relatively high levels of CGRP, which may be regulated by COX-2 at the transcriptional level. Further studies are needed to determine if CGRP levels are directly linked to OA pathology.

Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin- (IL-) 1β and AM in cultured synovial cells were also examined. CD11c+ macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side. AM expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1β treatment. Synovial macrophages also highly expressed RAMP3 compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited IL-1β expression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages.

To investigate the role of macrophages as a regulator and producer of nerve growth factor (NGF) in the synovial tissue (ST) of osteoarthritis (OA) joints, the gene expression profiles of several inflammatory cytokines in the ST, including synovial macrophages and fibroblasts, of OA mice (STR/Ort) were characterized. Specifically, real-time polymerase chain reaction analysis was used to evaluate the expression of tumor necrosis factor- (TNF-)α, interleukin- (IL-) 1β, IL-6, and NGF in CD11b+ and CD11b– cells isolated from the ST of a murine OA model. The effects of TNF-α, IL-1β, and IL-6 on the expression of NGF in cultured synovial cells were also examined. The expression of TNF-α, IL-1β, IL-6, and NGF in the ST of STR/Ort was higher than that in C57/BL6J mice. Compared to the CD11b– cell fraction, higher expression levels of TNF-α, IL-1β, and IL-6 were detected in the CD11b+ cell fraction, whereas no differences in the expression of NGF were detected between the two cell fractions. Notably, TNF-αupregulated NGF expression in synovial fibroblasts and macrophages and IL-1βupregulated NGF expression in synovial fibroblasts. IL-1βand TNF-αmay regulate NGF signaling in OA joints and be suitable therapeutic targets for treating OA pain.

Patients who undergo surgical repair of intercondylar eminence fracture may have postoperative problems despite good reduction. We used arthroscopy to evaluate the outcomes after surgery to repair intercondylar eminence fractures.Ten patients (8 men and 2 women; average age at the time of surgery 27.9 +/- 10.0 years, range from 14 to 50 years) with fracture of the tibial intercondylar eminence underwent an arthroscopic reduction and internal fixation with non-absorbable sutures. Preoperative radiological examination showed that there were one Meyer's type-II, eight type-IIIA and one type-IIIB fractures. Clinical symptoms and physical findings for all the patients were evaluated 1 year postoperatively. Radiographic assessment and the Lysholm rating scale were also utilized. Second-look arthroscopy was performed after 1 year when removing the implant. Arthroscopy was used to assess the appearance of the surface of the anterior cruciate ligament (ACL), check for the existence of cyclops and look for interposition of tissue in the lateral and medial joint spaces.One year after the surgery, all ten patients achieved bony union and had negative Lachman and anterior drawer tests. The average Lysholm knee score was 94.5 +/- 7.2 points (range 100-75 points). Arthroscopy showed an irregular surface on the ACL in two of the ten patients, cyclops in two patients, interposition in the lateral joint space in two patients and interposition in the medial joint space in one patient. In the two cases seen with an irregular surface, the ACL was covered with droopy fibrous tissue, but the substance of the ACL was intact. The two patients who had cyclops showed loss of knee extension (5~10 degrees), which was regained by subsequent resection of the cyclops. One patient who had an interposition into the lateral joint space complained of catching, which was released by resection of the interposing tissue.Arthroscopic refixation of the intercondylar eminence fracture provided bony union and a good clinical outcome. Cyclops syndrome is one of the causes of loss of knee extension, and soft tissue in the medial or lateral compartment is one of the causes of catching of knee after surgical repair of intercondylar eminence fracture. Cyclops syndrome, which may occur following ACL reconstruction, is one of the causes of loss of knee extension after surgical repair of intercondylar eminence fracture. In patients who have knee complaints, such as catching and loss of knee extension, a second-look arthroscopy is useful for identifying and correcting the problem.

Summary Recent studies have reported that calcitonin gene-related peptide (CGRP) contributes to joint pain. However, regulation of the CGRP/CGRP receptor signalling in osteoarthritis (OA) is not fully understood. To investigate the regulation of CGRP/CGRP receptor signalling by macrophages in the synovial tissue (ST) of OA joints, we characterized the gene expression profiles of CGRP and CGRP receptors in the ST of OA mice (STR/Ort). In addition, we examined whether macrophage depletion by the systemic injection of clodronate-laden liposomes affected the expression of CGRP and CGRP receptors in ST. CD11c+ macrophages in the ST of STR/Ort and C57BL/6J mice were analysed by flow cytometry. Real-time polymerase chain reaction (PCR) was used to evaluate the expression of interleukin (IL)-1β, CGRP, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in F4/80+ and F4/80− cells. The effects of IL-1β on the expression of CGRP and CLR by cultured synovial cells were also examined. The percentage of CD11c+ macrophages in the ST of STR/Ort was higher than that in C57/BL6J mice. Notably, the F4/80+ cell fraction expressed IL-1β highly, whereas the F4/80− cell fraction expressed CGRP, CLR, and RAMP1 highly. In addition, expression of the IL-1β and CLR genes was increased in ST, but was decreased upon macrophage depletion, and the IL-1β treatment of cultured synovial cells up-regulated CLR. Taken together, the present findings suggest that synovial macrophages are the major producers of IL-1β and regulators of CLR in OA mice. Therefore, macrophages and IL-1β may be suitable therapeutic targets for treating OA pain.

Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016.

Background To repair fractures with large bone defects or gaps, demineralized allogenic bone matrix (DBM) is often applied to the fracture site. However, studies have shown that the use of DBM alone has limited efficacy for repairing fractures. In the present study, we developed an allogenic demineralized bone powder (DBP) with basic fibroblast-derived growth factor containing a polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) from Clostridium histolyticum collagenase (ColH) and investigated the stimulatory effects of bFGF-PKD-CBD combined with allogenic DBP on bone growth in a mouse femur fracture model. Methods DBP mixed with either phosphate-buffered saline (PBS) (DBP/PBS), 0.58 nmol basic fibroblast growth factor (bFGF) (0.58 nmol DBP/bFGF), 0.058 nmol bFGF-PKD-CBD (0.058 nmol DBP/bFGF-PKD-CBD), or 0.58 nmol bFGF-PKD-CBD (0.58 nmol DBP/bFGF-PKD-CBD) was grafted into fracture sites. Results bFGF-PKD-CBD/DBP composite accelerates callus formation in a bone fracture model in mice and clearly showed that the composite also increases bone mineral density at fracture sites compared to bFGF/DBP. In addition, bFGF-PKD-CBD/DBP increased callus volume and bone mineral content to similar levels in fractures treated with a tenfold higher amount of bFGF at 4 weeks. Conclusions Our results suggest that bFGF-PKD-CBD/DBP may be useful for promoting fracture healing in the clinical setting.

Osteochondral allografting is a promising option for the treatment of large cartilage defects. However, because the cell viability of osteochondral tissues (OCTs) gradually reduces during storage at 4°C, methods for maintaining the cell viability of fresh OCTs are needed to improve transplantation outcomes. Here, we evaluated whether the supplementation of preservation solution with one of three different molecular weight forms of hyaluronic acid (HA) improved the viability of rat OCTs during long-term cold storage. The supplementation of University of Wisconsin (UW) solution with 800 kDa significantly improved the cell viability of OCT after 14 days at 4°C compared to nonsupplemented UW solution. In contrast, UW solution supplemented with either 1900 or 6000 kDa HA did not markedly improve the cell viability of the OCT. Real-time PCR analysis revealed that the levels of matrix metalloproteinases 2, 3, and 9 were significantly decreased in OCT stored in UW solution supplemented with 800 kDa HA. Although further studies in human OCT are warranted, these findings demonstrate that the use of 800 kDa HA in place of serum may be a suitable approach for the long-term preservation of osteochondral allografts designated for the repair of large cartilage defects in the clinical setting.

Background Once articular cartilage is destroyed, the intrinsic reparative ability is poor. Therefore, various techniques have been developed to repair articular defects. Many kinds of scaffolds have been used for cultured chondrocyte transplantation. In this study, we developed a sponge consisting of type II collagen. We investigated the influence of three-dimensional culture on the maintenance of the chondrocyte phenotype and on the redifferentiation of dedifferentiated chondrocytes. Methods Chondrocytes were isolated from the rib cartilage of rats and were cultured in plastic dishes for a week (P0). The cells were then dissociated with trypsin and subcultured for another 2 weeks (P1). Primary isolated chondrocytes were cultured in the type II collagen sponges for 3 weeks (S1). We compared the gene expression of S1 for chondrogenic markers with the expression of P0 and P1 by reverse transcription-polymerase chain reaction (RT-PCR). The cells were then dissociated with trypsin and subcultured for another 2 weeks (P1) and then another 6 weeks (P3). Cells of P1 were subsequently cultured in type II collagen sponges for 4 weeks (P1r). At each time point, gene expression of chondrogenic markers was examined by RT-PCR. Results Gene expression of COL2A1, COL10A1, and aggrecan in S1 was the same as in P0. Gene expression of COL10A1 and aggrecan in P1r was higher than in P1 and P3. Gene expression of COL1A1, COL2A1, and SOX9 in P1r was lower than in P1 and P3. Gene expression of ALP and osteocalcin in P1r was detected. Conclusions These results show that culture in type II collagen sponges could maintain the chondrocyte phenotype; however, dedifferentiated chondrocytes differentiated to hypertrophic chondrocytes. These finding suggest that the complex of cells and scaffolds with primary cells was more useful than that with dedifferentiated chondrocytes in laboratory and clinical application.

Background: Low back pain (LBP) is the most commonly reported injury in Olympic class sailing, accounting for up to 53% of all injuries. Despite the propensity for LBP in sailors, there has been limited investigation of risk factors associated with seasonal LBP incidence. Musculoskeletal screening has proven effective in identifying risk factors for seasonal injury in athletic populations, although no such research has been reported in sailors. The aim of this study was to determine whether musculoskeletal screening could predict seasonal LBP in this population. Methods: A 12-month (October 2011–2012) retrospective analysis of injury surveillance data was performed for members of the Australian Sailing Team, state representative sailing teams, and Australian Sailing Team invitees (age 16–30 years, N=22). Musculoskeletal screening, incorporating various mobility, stability and strength tests, was undertaken at the start of the sailing season. Recorded seasonal injury data were classified according to the Orchard Injury Classification System Version 10 to determine the incidence of LBP. Logistic regression analysis was performed in order to identify any screening measures predictive of LBP. Results: An injury incidence rate of 2.7 (injury requiring treatment) and 0.5 (injury resulting in modified/lost participation) per athlete were recorded, with the lumbar spine accounting for the main site of injury (28% and 36%, respectively). In terms of athlete disability, LBP accounted for the highest number of days of modified participation (average 28 days), and the second highest number of days of lost participation (average 16 days). Over the 12-month review period 75% of LBP occurred in the second six monthsof the season.Nosignificantlypredictive relationshipswere observed between any of the musculoskeletal screening measures and LBP incidence. However, increasing age was significantly (p=0.03) associated with increased risk of LBP, with an OR of 1.46 (95% CI 1.04–2.04). Discussion: Currentmusculoskeletal screeningprotocols donot adequately assess the risk of seasonal LBP in Olympic class sailors. Given that older Olympic class sailors are more at risk of experiencing seasonal LBP, and potential disability throughmodified or lost participation, coaches and sportsmedicine support staff should implement appropriate intervention strategies that limit the risk of seasonal LBP to these individuals. Consideration should be given to age-specific lumbar spine functioning, particularly in the second half of the season when athletes are engaged in significant international travel and competition. Future research should focus on identifying suitable musculoskeletal screening protocols that can predict seasonal LBP in Olympic class sailing.