Yuichiro Matsui

Accelerated development of aging-associated and instability-induced osteoarthritis in osteopontin-deficient mice

OBJECTIVE To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions. METHODS Both instability-induced and aging-associated OA models were generated using OPN-deficient (OPN-/-) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage. RESULTS OPN deficiency exacerbated both aging-associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA. CONCLUSION OPN plays a pivotal role in the progression of both instability-induced and aging-associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss.

Interruption of Glycosphingolipid Synthesis Enhances Osteoarthritis Development in Mice

OBJECTIVE Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. GSL expression is decreased in the articular cartilage of humans with osteoarthritis (OA). This study was undertaken to determine the functional role of GSLs in cartilage metabolism related to OA pathogenesis in mice. METHODS We generated mice with knockout of the chondrocyte-specific Ugcg gene, which encodes an initial enzyme of major GSL synthesis, using the Cre/loxP system (Col2-Ugcg(-/-) mice). In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of GSLs on the cartilage degradation process. RESULTS Although Col2-Ugcg(-/-) mice developed and grew normally, OA changes in these mice were dramatically enhanced with aging, through the overexpression of matrix metalloproteinase 13 and chondrocyte apoptosis, compared to their wild-type (WT) littermates. Col2-Ugcg(-/-) mice showed more severe instability-induced pathologic OA in vivo and interleukin-1α (IL-1α)-induced cartilage degradation in vitro. IL-1α stimulation of chondrocytes from WT mice significantly increased Ugcg messenger RNA expression and up-regulated GSL metabolism. CONCLUSION Our results indicate that GSL deficiency in mouse chondrocytes enhances the development of OA. However, this deficiency does not affect the development and organization of cartilage tissue in mice at a young age. These findings indicate that GSLs maintain cartilage molecular metabolism and prevent disease progression, although GSLs are not essential for chondrogenesis of progenitor and stem cells and cartilage development in young mice. GSL metabolism in the cartilage is a potential target for developing a novel treatment for OA.

Predictive factors of long head of the biceps tendon disorders—the bicipital groove morphology and subscapularis tendon tear

BACKGROUND Disorders of the long head of the biceps (LHB) tendon contribute to anterior shoulder pain. Although LHB tendon disorders are associated with rotator cuff disease, distinguishing between biceps and rotator cuff pathology is difficult. The objective was to identify the predictors of LHB tendon disorders associated with a supraspinatus tear. METHODS In 55 patients (average age, 65 years) undergoing arthroscopic rotator cuff repair, bicipital groove morphology were assessed using computed tomography, and subscapularis tear and bicipital groove effusion were assessed using magnetic resonance imaging, retrospectively. The LHB tendon was evaluated arthroscopically according to the Lafosse classification. Univariate and multivariate ordinal logistic regression analyses were conducted for injury grade with all covariates. RESULTS The arthroscopic evaluation of the LHB tendon showed that there were 23 shoulders classified as grade 0, 15 as grade 1, and 17 as grade 2. Univariate logistic regression analysis showed that the width and depth, a medial spur of the bicipital groove, and a subscapularis tear were significantly associated with LHB tendon disorders. Multivariate ordinal logistic regression analysis identified a medial spur and subscapularis tear as significant predictors of LHB tendon disorders. CONCLUSIONS The preoperative computed tomography and magnetic resonance images, notably the presence of a spur on the bicipital groove or a subscapularis tear, were useful for identifying LHB tendon disorders. When these are found in preoperative images, the clinician should evaluate the patient for the presence of an LHB tendon disorder as a pain generator.

Down‐regulation of cathepsin K in synovium leads to progression of osteoarthritis in rabbits

OBJECTIVE The hypothesis of this study was that synovial factors playing a pivotal role in the pathogenesis of osteoarthritis (OA) and thus gene expression in the synovium would be altered at the initial stage of OA. The aims of this study were to identify the candidate genes in synovium related to OA initiation, to evaluate cartilage degeneration after knockdown of the gene using small interfering RNA (siRNA) gene silencing in the knee joints at the initial stage of OA, and to determine the potential role of the knocked-down gene in OA initiation. METHODS Genes overexpressed in synovium at the initial stage of disease in a rabbit model of anterior cruciate ligament transection (ACLT)-induced OA were identified using the suppression subtractive hybridization technique and differential screening. Candidate gene expression in the synovium of the knees of rabbits with OA was manipulated with electroporation-assisted siRNA transduction 4 times before and after operation. Four weeks after surgery, histologic analysis was performed. RESULTS Cathepsin K gene and protein expression was significantly up-regulated in synovium at the initial stage of OA in rabbits. Down-regulation of cathepsin K in synovium at the initial stage of OA significantly accelerated cartilage degeneration. CONCLUSION These results indicate that cathepsin K plays a protective role in cartilage degeneration at the initial stage of OA. We believe that the current results obtained from models of the early phase of OA will provide useful information for developing a novel strategy to prevent disease progression.

Clinical and Radiological Results of Radiolunate Arthrodesis for Rheumatoid Arthritis: 22 Wrists Followed for an Average of 7 Years

PURPOSE To evaluate the clinical and radiological results of radiolunate (RL) arthrodesis for rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs and/or biologicals with an average of 7 years of follow-up. In addition, we compared the results in advanced stages with those in less advanced stages in patients with comparatively low disease activity of RA. METHODS This study included RL arthrodesis for 22 wrists in 19 patients with comparatively low disease activity of RA. The mean follow-up period was 7 years (range, 2-16 y). Fourteen wrists with Larsen classification grade III and 8 wrists with grade IV were included in this study. The range of motion was calculated, and clinical scores were graded using the Mayo wrist score and the Stanley classification. The carpal height ratio (CHR) and ulnar translation (UT) were determined from the radiographs. RESULTS All wrists achieved radiographic fusion. Clinical scores were markedly improved, although there was a decrease in flexion. The Larsen grade did not deteriorate during follow-up. CHR and UT improved immediately after operation and remained good through the final follow-up. Although the flexion/extension range of motion of the grade IV wrists was smaller than that of the grade III wrists at follow-up, both groups obtained good clinical results. CONCLUSIONS Our results for RL arthrodesis were clinically and radiologically better than those of previous reports. Control of the disease activity of RA could theoretically be a factor in obtaining good long-term clinical and radiographic outcomes. RL arthrodesis is our recommended procedure for the RA wrist even in the advanced stage. LEVEL OF EVIDENCE Therapeutic IV.

Bizarre parosteal osteochondromatous proliferation (Nora’s lesion) affecting the distal end of the ulna: a case report

BackgroundBizarre parosteal osteochondromatous proliferation (BPOP), first described by Nora et al. in 1983 and therefore termed “Nora’s lesion”, is a rare lesion that occurs in the short bones of the hands and feet and eventually presents as a parosteal mass. Reports of BPOP in the long bones are very rare. A benign disease, BPOP does not become malignant, although a high rate of recurrence following surgical resection is reported. Because of its atypical imaging findings and histopathological appearance, a BPOP might be misdiagnosed as a malignant tumor such as an osteochondroma with malignant transformation, a parosteal osteosarcoma, or a periosteal osteosarcoma.Case presentationA 58-year-old woman complained of left ulnar wrist pain at the time of her initial presentation. Plain x-rays showed ectopic calcifications in and around the distal radioulnar joint, which supported the diagnosis of subacute arthritis with hydroxyapatite crystal deposition. She was initially given a wrist brace and directed to follow-up, but her persistent pain required the administration of corticosteroid injections into the distal radioulnar joint. Increasing ulnar wrist joint pain and limited forearm pronation and wrist flexion necessitated computed tomography and contrast-enhanced magnetic resonance imaging. BPOP was diagnosed based on the preoperative imaging studies, and a resection of the lesion was performed along with the decortication of the underlying the cortical bone to reduce recurrence rates. The diagnosis of BPOP was confirmed by pathologic examination. Two years after surgery, the patient has no subsequent pain complaints and an improved range of motion.ConclusionsBPOP affecting the distal end of the ulna is exceedingly rare. Because BPOP was diagnosed primarily based upon preoperative imaging findings in our patient, decortication of the underlying cortical bone was performed to reduce recurrence rates. Further careful follow-up in these patients is essential, despite the non-recurrence of the lesion.

Blood Flow Changes in Subsynovial Connective Tissue on Contrast-Enhanced Ultrasonography in Patients With Carpal Tunnel Syndrome Before and After Surgical Decompression: Blood Flow in Subsynovial Tissue in Carpal Tunnel Syndrome

Although qualitative alteration of the subsynovial connective tissue in the carpal tunnel is considered to be one of the most important factors in the pathophysiologic mechanisms of carpal tunnel syndrome (CTS), little information is available about the microcirculation in the subsynovial connective tissue in patients with CTS. The aims of this study were to use contrast‐enhanced ultrasonography (US) to evaluate blood flow in the subsynovial connective tissue proximal to the carpal tunnel in patients with CTS before and after carpal tunnel release.

Autologous Osteochondral Mosaicplasty for Centrally and Laterally Located, Advanced Capitellar Osteochondritis Dissecans in Teenage Athletes: Clinical Outcomes, Radiography, and Magnetic Resonance Imaging Findings:

Background: Autologous osteochondral mosaicplasty (ie, mosaicplasty) results in satisfactory clinical outcomes and reliable return to play for patients with large or unstable lesions due to osteochondritis dissecans (OCD) of the humeral capitellum. However, the association between the healing of the reconstructed cartilage and clinical outcomes remains unclear. Purpose: To evaluate the efficacy of mosaicplasty in teenage athletes through use of clinical scores and imaging. The secondary purpose was to compare the clinical outcomes with images of centrally and laterally located lesions. Study Design: Case series; Level of evidence, 4. Methods: This study analyzed 22 elbows (all male patients; mean age, 13.5 ± 1.2 years) with capitellar OCD managed with mosaicplasty. Patients were divided into 2 groups according to the location of the lesions: central (10 patients) and lateral (12 patients). Evaluation was performed through use of the clinical rating system of Timmerman and Andrews, plain radiographs, and magnetic resonance imaging (MRI; the cartilage repair monitoring system of Roberts). The mean follow-up period was 27.5 months (range, 24-48 months). Results: Lateral lesions were significantly larger than central lesions (147.1 ± 51.9 mm2 vs 95.5 ± 27.4 mm2, P = .01). No other significant differences were found between central and lateral lesions. Timmerman and Andrews scores for both central and lateral lesions improved significantly from 125.0 ± 30.1 points and 138.3 ± 34.5 points preoperatively to 193.5 ± 11.3 points and 186.7 ± 18.1 points, respectively, at final follow-up (P < .0001, P < .0001). Radiography identified complete graft incorporation in all cases and the absence of severe osteoarthritic changes or displaced osteochondral fragments. In the lateral group, the radial head ratio at final follow-up (1.83 ± 0.23) was significantly larger than the preoperative findings (1.75 ± 0.14, P = .049). The quality of joint surface reconstruction was found to be acceptable for central and lateral lesions on MRI evaluation. Conclusion: Mosaicplasty resulted in satisfactory clinical outcomes and smooth cartilage surface integrity in teenage athletes with OCD on their return to competition-level sports activities irrespective of lesion location.

Increased expression of αv integrin as a regulator of fibrosis in Dupuytren’s nodules

Although Dupuytren’s contracture is characterized by increased transforming growth factor-β1 (TGF-β1) and fibrosis in the palmar fascia, the relationship between TGF-β1 and integrins, which are considered to be related to fibrosis, remains unclear. We investigated the involvement of TGF-β1 and integrins in the pathological palmar fascia of Dupuytren’s contracture. Seven patients underwent partial fasciectomy for treatment of this disease. The nodule and cord were isolated from the fascial tissues of the patients. Control fasciae were obtained from seven patients with carpal tunnel syndrome. Immunohistochemical analysis was performed to detect the fibrosis marker α-smooth muscle actin and integrins in the fascial tissues. The expression of TGF-β1 and integrins was assessed by real-time polymerase chain reaction. The results suggest that nodules may be areas involved in activation of fibrosis in the fascia, associated with increased expression of TGF-β1 and αv integrin. Thus, αv integrin may contribute to fibrosis in Dupuytren’s contracture by activating TGF-β1. Level of Evidence: IV