Degradation of cartilage type II collagen precedes the onset of osteoarthritis following anterior cruciate ligament rupture

Abstract

Objective: To determine if degradation of cartilage matrix in primary osteoarthritis (OA) or in OA secondary to rupture of the anterior cruciate ligament (ACL) is a gradual response to excessive loading or an early, initiating event in the disease process.

Methods: Biopsy samples were obtained from the low-weight-bearing articular cartilage of the intercondylar notch, in patients undergoing knee arthroscopy (ACL injury) or arthroplasty (late-stage primary OA) or in controls. In some cases, biopsy samples were also removed from the high-weight-bearing articular cartilage of the femoral condyles. Biopsy specimens were extracted and assayed for total and denatured type II collagen (CII) by inhibition enzyme-linked immunosorbent assay and for proteoglycan using a colorimetric method. All patients were assessed radiographically for cartilage erosion. In addition, the cartilage of patients with ACL injury was assessed at arthroscopy, and the knee function of patients with primary OA was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results: Increased CII degradation was detected in the low- as well as the high-weight-bearing cartilage of patients with late-stage OA, and there was a positive correlation between the percentage denatured collagen and the WOMAC score. Most of the patients with ACL injury had no clinical signs of OA or macroscopic cartilage erosion. However, the low-weight-bearing articular cartilage from these patients showed a significant increase in CII degradation, similar to that observed in late-stage OA. The proteoglycan content of articular cartilage did not change significantly in patients with OA or ACL injury compared with controls.

Conclusion: CII degradation is an early event following ACL injury and is unlikely to be a direct result of mechanical loading, since it was observed in cartilage obtained from a low-weight-bearing site.