Sunk I-G et al. (2007) Increased expression of discoidin domain receptor 2 is linked to the degree of cartilage damage in human knee joints. Arthritis Rheum 56: 3685–3692

Osteoarthritis (OA) is characterized by proteoglycan loss, degradation of type II collagen and subsequent destruction of articular cartilage matrix. Animal experiments have provided strong evidence for the involvement of a tyrosine kinase receptor for type II collagen, discoidin domain receptor 2 (DDR2), in the pathogenesis of OA.

Sunk et al. analyzed human osteoarthritic articular cartilage obtained from 16 patients (mean age 64.8 years) for expression of DDR2 and matrix metalloproteinase 13 (MMP13), because DDR2 expression and activation has previously been shown to result in increased synthesis of this MMP. Levels of DDR2 and MMP13 were found to directly correlate with the severity of cartilage damage.

Chondrocytes were obtained from the articular cartilage samples and cultured for 24 hours. Exposure to type II collagen resulted in increased expression of DDR2 and MMP13. The authors hypothesize that this process might be integral to the initiation of type II collagen degradation in early OA, since disruption of the pericellular microenvironment could expose collagen type II fibrils to chondrocytes.

Blockade of DDR2 is, therefore, a potential therapeutic option for patients with early OA.