Objective: Mechanical stress is one of the most exacerbating factors on knee osteoarthritis (OA). We recently reported the effect of shear stress on OA progression in vivo using controlled abnormal tibial translation (CATT), which suppressed shear stress in vivo due to ACL transection (ACL-T). However, surgical ACL-T mice models were used, thus effect of shear stress cannot be clarified exactly. So, we aimed to establish a novel Non-Invasive ACL-T without intra-articular injuries and reveal the onset mechanism of knee OA induced by shear stress.
Design: First, twelve-week-old C57BL/6 male mice were used to make a novel Non-Invasive ACL-T model. After creating the model, injuries of intra-articular tissues were observed histologically, macroscopically, and morphologically. Next, twelve-week-old C57BL/6 male mice were categorized into ACL-T, CATT, and Sham groups. After 2,4 and 8 weeks, we performed the anterior drawer test, safranin-O/fast green staining, and immunohistochemical staining for MMP-3 and TNF-α.
Results: In a novel Non-Invasive ACL-T model, no injuries, including cartilage, meniscus, and bone were not observed except ACL rupture. Regarding OA progression, the anterior tibial translation in the ACL-T group was significantly higher than that of the other groups at all weeks, and cartilage degeneration in the ACL-T group increased significantly compared with the other groups at 8 weeks. Although synovitis score in the ACL-T and CATT groups was significantly higher than the Sham group at 2 and 8 weeks, there were no differences between the ACL-T and CATT groups. In addition, the MMP-3 positive cell rate in the cartilage of the ACL-T group was higher than the other groups at 4 and 8 weeks. However, that in the synovium of the ACL-T group was higher than the other groups at 8 weeks. TNF-α positive cell rates in both cartilage and synovium were not changed between the ACL-T and CATT groups.
Conclusion: We have successfully established a new Non-Invasive ACL-T model without intra-articular tissue damage, which induces knee OA due to shear stress. In the OA progression caused by shear stress, chondrocytes first showed a molecular biological response, leading to a local increase in MMP-3. On the other hand, synovitis is not directly induced by mechanical stress but is indirectly caused by intra-articular degeneration associated with knee OA progression.