Concurrent Joint Contact in Anterior Cruciate Ligament Injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis.

Abstract

Anterior Cruciate Ligament (ACL) injury initiates post-traumatic osteoarthritis (PTOA) via two distinct processes: initial direct contact injury of the cartilage surface during ACL injury, and secondary joint instability due to the ACL deficiency. Using the well-established Compression-induced ACL rupture method (ACL-R) and a novel Non-Compression ACL-R model, we aimed to reveal the individual effects of cartilage compression and joint instability on PTOA progression after ACL injury in mice. Twelve-week-old C57BL/6J male were randomly divided to three experimental groups: Compression ACL-R, Non-Compression ACL-R, and Intact. Following ACL injury, we performed joint laxity testing and microscopic analysis of the articular cartilage surface at 0 days, in vivo optical imaging of matrix-metalloproteinase (MMP) activity at 3 and 7 days, and histological and microCT analysis at 0, 7, 14, and 28 days. The Compression ACL-R group exhibited a significant increase of cartilage roughness immediately after injury compared with the Non-Compression group. At 7 days, the Compression group exhibited increased MMP-induced fluorescence intensity and MMP-13 positive cell ratio of chondrocytes. Moreover, histological cartilage degeneration was observable in the Compression group at the same time point. Sclerosis of tibial subchondral bone in the Compression group was more significantly developed than in the Non-Compression group at 28 days. Both Compression and Non-Compression ACL injury initiated PTOA progression due to joint instability. However, joint contact during ACL rupture also caused initial micro-damage on the cartilage surface and initiated early MMP activity, which could accelerate PTOA progression compared to ACL injury without concurrent joint contact.