Osteoarthritis (OA) is a chronic debilitating joint disease

characterized by degeneration of the cartilage and loss of the cartilage matrix

and it is clinically manifested as joint pain. Osteopontin (OPN) is a glycoprotein that is abnormally expressed in the bone and cartilage tissues and plays a vital role in various pathological processes such as the osteoarthritic inflammatory response and endochondral ossification. The focus of our study is to investigate the therapeutic potential and specific role of OPN in OA. Using morphological comparisons

we found that the cartilage was severely worn-out and there was a significant loss of the cartilage matrix in OA. OPN

CD44

and hyaluronic acid (HA) synthase 1 (HAS1) were highly expressed

and the anabolism of HA was significantly higher in the OA chondrocytes than in the control chondrocytes. Additionally

we treated the OA chondrocytes with small interfering RNA (siRNA) targeting OPN

recombinant human OPN (rhOPN)

and a combination of rhOPN and anti-CD44 antibodies. Furthermore

in vivo

experiments were performed in mice. We found that OPN upregulated the expression of downstream HAS1 and increased the anabolism of HA through CD44 protein expression in OA mice compared with those in control mice. Moreover

intra-articular injection of OPN in mice with OA significantly inhibited OA progression. In summary

OPN initiates an intracellular cascade via CD44 which results in an anabolic increase in HA levels

thereby inhibiting OA progression. Therefore

OPN is a promising therapeutic agent in precision treatment of OA.