Mechanistic and Therapeutic Insights Into the Function of Netrin1 in the Joint Tissue of Osteoarthritis

Abstract

Osteoarthritis is the most prevalent degenerative joint disease, characterized by the trauma and inflammation of the cartilage and subchondral bone, leading to cartilage degradation, reduced bone mass, joint pain, and functional impairment. Articular cartilage and subchondral bone is a complex functional structural complex, in which Netrin protein family and its transmembrane protein receptors such as Unc5b, DCC and A2B are widely expressed. The Netrin family, part of the laminin superfamily, includes various subtypes, with Netrin1 being notably researched for its regulatory role in bone tissue.Netrin1 protein can activate downstream signaling pathways that affect cell function and regulate the functional activity of various cells in joint tissue after binding to its receptors. Studies have pointed out that anti-Netrin1 treatment can significantly alleviate osteoarthritis and other arthritis lesions, as well as reduce neuropathic pain. This review aims to explore the function of the Netrin1 protein and its receptors across joint structures, discussing their potential regulatory mechanisms and implications for treating diseases like osteoarthritis.