Tawaratsumida H., Iuchi T., Masuda Y., Ide T., Maesako S., Miyazaki T., Ijuin T., Maeda S., Taniguchi N. . Zoledronate alleviates subchondral bone collapse and articular cartilage degeneration2024 · 記述言語： 日本語 出版者・発行元： Osteoarthritis and Cartilage Objective: To evaluate the humeral head bone volume of patients with cuff tear arthropathy (CTA) and examine the therapeutic effect of zoledronate in a rat modified model of CTA (mCTA). Design: The bone mass in patients with CTA was measured using Hounsfield units from CT images. The mCTA was induced by transecting the rotator cuff, biceps brachii tendon, and superior half of the joint capsule in adult rat shoulders. A single subcutaneous injection of zoledronate was followed by bone histomorphometry and immunohistochemistry of the humeral head, as well as the Murine Shoulder Arthritis Score (MSAS) assessment. Results: The humeral head bone volume was decreased in patients with CTA. In the mCTA model, M1 macrophages were increased in the synovium and were decreased by zoledronate treatment. The increased expressions of TNF-α, IL-1β and IL-6 in mCTA synovium and articular cartilage were suppressed in the zoledronate-treated mCTA group. The expression of catabolic enzymes in the articular cartilage and MSAS showed similar results. The zoledronate-treated mCTA group showed a decreased subchondral bone collapse with a decreased RANKL/OPG expression ratio and a suppressed number of osteoclasts compared with the control mCTA group. The enhanced expressions of HMGB1 and S100A9 in the mCTA shoulders were eliminated in the zoledronate-treated mCTA group. Conclusions: The humeral head subchondral bone was decreased in patients with CTA. In the mCTA model, the collapse and osteoarthritic changes were prevented by zoledronate administration. Zoledronate seemed to suppress the number of M1 macrophages in the synovium and osteoclasts in the subchondral bone. DOI： 10.1016/j.joca.2024.08.005 Scopus PubMed
Ijuin T., Iuchi T., Tawaratsumida H., Masuda Y., Tokushige A., Maeda S., Taniguchi N. . Development of a novel animal model of rotator cuff tear arthropathy replicating clinical features of pr2023 · 記述言語： 日本語 出版者・発行元： Osteoarthritis and Cartilage Open Objective: To establish an animal model of modified cuff tear arthropathy (mCTA) in order to better replicate the pathophysiology associated with rotator cuff tear-induced humeral head collapse. Design: mCTA was induced by transection of the rotator cuff, the long head of the biceps brachii (LHB), and superior half of the joint capsule in the right shoulder of 12-week-old rats; the left shoulder underwent sham surgery. The severity of CTA was quantitated using the Murine Shoulder Arthritis Score (MSAS). The trabecular bone of the humeral head and metaphysis was analyzed using bone histomorphometry. The expression of proinflammatory cytokines and catabolic enzymes was evaluated immunohistochemically. Results: In the mCTA model, the MSAS increased starting from 2 weeks after induction, and there was notable subchondral bone collapse with fibrous cells at 4 weeks. The mCTA cartilage exhibited positive staining for TNF-α, IL-1β/6, MMP-3/13, and ADAMTS5. The trabecular bone volume was reduced not only in the subchondral bone but also in the metaphysis of the humeri, and bone resorption was enhanced in these areas. In the collapsed subchondral bone, both bone formation and resorption were increased. The fibrous cells showed expression of TNF-α, IL-6, and MMP-13, along with specific markers of mesenchymal stem cells. Furthermore, the fibrous cells showed osteoblastic characteristics (RUNX2-positive) and expressed RANKL. Conclusions: The LHB and the capsuloligamentous complex are critical stabilizers of the glenohumeral joint, serving to prevent the advancement of CTA following massive rotator cuff tears. Fibrous cells appear to play a role in the humeral head bone resorption. DOI： 10.1016/j.ocarto.2023.100389 Scopus PubMed
Sakuma D., Ishidou Y., Fujimoto Y., Nakamura S., Ijuin T., Nagano S., Taniguchi N. . Finite element analysis of mechanical stress of the hip joint in patients with posterior pelvic inclination2022 · 記述言語： 日本語 出版者・発行元： World Academy of Sciences Journal Abnormal mechanical loading is a main external factor affecting the development of osteoarthritis (OA). Excessive posterior pelvic inclination may decrease the loading area of the acetabulum, increasing mechanical stress to the articular surface and resulting in hip OA. However, exactly how much posterior pelvic inclination produces an excessive load on the articular surface remains unknown. The present study investigated the mechanical stress of 27 hips in 19 women [unilateral (right or left) hip joints of 11 women and bilateral (right and left) hip joints of 8 women were analyzed] with or without acetabular dysplasia by finite element analysis. Patient-specific finite element models were constructed from computed tomography data obtained in the supine position. The posterior pelvic inclination in the models was changed from 0 to 30 degrees in five-degree increments. The association between equivalent stress in the hip joint and the pelvic inclination or acetabular dysplasia was analyzed. The equivalent stress for the femoral head in the original position was 0.97 MPa (0.91-1.01) in normal hip joints and 1.18 MPa (1.00-1.28) in hips with acetabular dysplasia (P=0.023). The equivalent stress significantly increased at >25 degrees of posterior inclination. In normal hips, when the pelvic posterior inclination was increased by 25 and 30 degrees, the equivalent stress was 1.21 (1.11-1.35) and 1.24 (1.20-1.47) MPa, respectively (P=0.029 and 0.010, respectively). The mechanical stress of normal hip joints serially increased as the posterior pelvic inclination increased, reaching a level almost equivalent to that of hip joints with acetabular dysplasia at 25 degrees of posterior inclination. On the whole, the present study demonstrates that posterior pelvic inclination may be a mechanical factor affecting the development of OA in patients without acetabular dysplasia, particularly when the posterior inclination exceeds 25 degrees. DOI： 10.3892/WASJ.2022.145 Scopus
Jokoji G., Maeda S., Oishi K., Ijuin T., Nakajima M., Tawaratsumida H., Kawamura I., Tominaga H., Taketomi E., Ikegawa S., Taniguchi N. . CDC5L promotes early chondrocyte differentiation and p2021 · 記述言語： 日本語 出版者・発行元： Journal of Biological Chemistry Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common pathological condition that causes intractable myelopathy and radiculopathy, mainly the result of an endochondral ossification-like process. Our previous genome-wide association study identified six susceptibility loci for OPLL, including the cell division cycle 5-like (CDC5L) gene region. Here, we found CDC5L to be expressed in type II collagen-producing chondrocyte-like fibroblasts in human OPLL specimens, as well as in differentiating ATDC5 chondrocytes. Cdc5l siRNA transfection in murine chondrocytes decreased the expression of the early chondrogenic genes Sox9 and Col2a1, diminished the cartilage matrix production, and enhanced the expression of parathyroid-hormone-related protein (a resting chondrocyte marker). We also showed that Cdc5l shRNA suppressed the growth of cultured murine embryonal metatarsal cartilage rudiments and that Cdc5l knockdown suppressed the growth of ATDC5 cells. Fluorescence-activated cell sorting analysis revealed that the G2/M cell cycle transition was blocked; our data showed that Cdc5l siRNA transfection enhanced expression of Wee1, an inhibitor of the G2/M transition. Cdc5l siRNA also decreased the pre-mRNA splicing efficiency of Sox9 and Col2a1 genes in both ATDC5 cells and primary chondrocytes; conversely, loss of Cdc5l resulted in enhanced splicing of Wee1 pre-mRNA. Finally, an RNA-binding protein immunoprecipitation assay revealed that Cdc5l bound directly to these target gene transcripts. Overall, we conclude that Cdc5l promotes both early chondrogenesis and cartilage growth and may play a role in the etiology of OPLL, at least in part by fine-tuning the pre-mRNA splicing of chondrogenic genes and Wee1, thus initiating the endochondral ossification process. DOI： 10.1016/j.jbc.2021.100994 Scopus PubMed
