TY - JOUR T1 - Effect of differences in mechanical stress in vivo on the onset and progression of knee osteoarthritis JF - bioRxiv DO - 10.1101/2021.06.04.447099 SP - 2021.06.04.447099 AU - Kohei Arakawa AU - Kei Takahata AU - Yuichiro Oka AU - Kaichi Ozone AU - Sumika Nakagaki AU - Saaya Enomoto AU - Kenji Murata AU - Naohiko Kanemura AU - Takanori Kokubun Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/05/2021.06.04.447099.abstract N2 - Objective The effect of the type of mechanical stress on OA onset has not been clarified. The aim of this study was to establish a new model that reproduces the type and increase and decrease of mechanical stress in vivo and to clarify the differences in the mechanism of knee OA onset and progression among the models.Design To reproduce the difference in mechanical stress, we used the anterior cruciate ligament transection (ACL-T) model and the destabilization of the medial meniscus (DMM) model. In addition, we created a controlled abnormal tibial translation (CATT) model and a controlled abnormal tibial rotation (CATR) model that suppressed the joint instability of the ACL-T and DMM model, respectively. These four models reproduced the increase and decrease in shear force due to joint instability and compressive stress due to meniscal dysfunction. We performed joint instability analysis with soft X-ray, micro computed tomography analysis, histological analysis, and immunohistological analysis in 4 and 6 weeks.Results Joint instability decreased in the CATT and CATR groups. The meniscus deviated in the DMM and CATR groups. Chondrocyte hypertrophy increased in the ACL-T and DMM groups with joint instability. In the subchondral bone, bone resorption was promoted in the ACL-T and CATT groups, and bone formation was promoted in the DMM and CATR groups.Conclusions Increased shear force causes articular cartilage degeneration and osteoclast activation in the subchondral bone. In contrast, increased compressive stress promotes bone formation in the subchondral bone earlier than articular cartilage degeneration occurs.Competing Interest StatementThe authors have declared no competing interest. ER -