Increased expression of the collagen receptor discoidin domain receptor 2 in articular cartilage as a key event in the pathogenesis of osteoarthritis.

Objective: To investigate the role of the collagen receptor discoidin domain receptor 2 (DDR-2) in the pathogenesis of osteoarthritis (OA).

Methods: Histologic and immunohistochemical analyses were performed to characterize femoral head cartilage from 7 patients with OA and 4 patients with fracture, as well as articular cartilage from the knee joints of mice with surgically induced OA. Gene constructs encoding human Raf kinase inhibitor protein (RKIP), DDR-2 lacking the discoidin (DS) domain (DeltaDS-DDR-2) or the protein tyrosine kinase (PTK) core (DeltaPTK-DDR-2), DDR-2 containing a substitution of tyrosine for alanine at position 740 (Y740A), and luciferase driven by the matrix metalloproteinase 13 (MMP-13) promoter were transfected into human chondrocyte cell lines.

Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice.

Human genetic studies indicate that mutations in type IX and XI collagens result in early-onset osteoarthritis (OA) with a wide spectrum of osteochondrodysplasia. However, a convincing causal chain of events underlying the role of these collagen mutations in the pathogenesis of OA has not been elucidated. Here we show that the expression of a cell surface collagen receptor, discoidin domain receptor 2 (DDR2), is increased in chondrocytes of the articular cartilage of knee joints in mice that develop OA as a result of a heterozygous mutation in type XI collagen.