Mechanistic Insight on the Interaction between OPN and Integrin ανβ3 in Osteoarthritis

Osteoarthritis (OA) is a joint disease characterized by cartilage degeneration. Osteopontin (OPN) is involved in the initiation, repair, and maintenance of metabolic homeostasis in normal articular cartilage. This study investigated the role of OPN and its interaction with the integrin alpha nu beta 3 receptor in the expression of hyaluronic acid (HA) in OA chondrocytes. Overexpression of OPN significantly increased the expression of integrin alpha nu beta 3 and hyaluronic acid synthases (HAS) and synthesis of HA. Depleting OPN in OA chondrocytes showed the opposite trend for integrin alpha;nu beta 3, HAS, and HA. Nonspecifically and specifically blocking integrin receptor using GRGDSP and integrin alpha nu beta 3 antibody downregulated HAS and HA; both were inhibited to similar extents. The expression of HAS and HA was predominantly regulated by the interaction between OPN and integrin alpha nu beta 3. Taken together, we have delineated the importance of the OPN/integrin alpha nu beta 3/HAS/HA axis in OA and identified OPN as a promising candidate for molecular therapy for use in patients with OA.