Ablation of collagen XII disturbs joint extracellular matrix organization and causes patellar subluxation

Collagen XII, belonging to the fibril-associated collagens, is a homotrimeric secreted extracellular matrix (ECM) protein encoded by the COL12A1 gene. Mu-tations in the human COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome leading to skeletal abnormalities and muscle weakness. Here, we stud-ied the role of collagen XII in joint pathophysiology by analyzing collagen XII defi-cient mice and human patients. We found that collagen XII is widely expressed across multiple connective tissue of the developing joint. Lack of collagen XII in mice destabilizes tendons and the femoral trochlear groove to induce patellar subluxation in the patellofemoral joint. These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degenera-tion. Moreover, patellar subluxation was also identified as a clinical feature of hu-man patients with collagen XII deficiency. The results provide an explanation for joint hyperlaxity in mice and human patients with collagen XII deficiency.

Automated summary

This study investigated the role of collagen XII in joint pathophysiology by analyzing collagen XII deficient mice and human patients. Collagen XII was found to be widely expressed in developing joints. Lack of collagen XII in mice destabilized tendons and femoral trochlear groove, leading to patellar subluxation. This clinical feature was also identified in human patients with collagen XII deficiency, providing an explanation for joint hyperlaxity.