IgSF11 deficiency alleviates osteoarthritis in mice by suppressing early subchondral bone changes

Abstract

Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and is thus also accompanied by local inflammation, subchondral bone changes, and persistent pain. However, our understanding of the underlying subchondral bone dynamics during OA progression is poor. Here, we demonstrate the contribution of immunoglobulin superfamily 11 (IgSF11) to OA subchondral bone remodeling by using a murine model. In particular, IgSF11 was quickly expressed by differentiating osteoclasts and upregulated in subchondral bone soon after destabilization-of-the-medial-meniscus (DMM)-induced OA. In mice, IgSF11 deficiency not only suppressed subchondral bone changes in OA but also blocked cartilage destruction. The IgSF11-expressing cells in OA subchondral bone were found to be involved in osteoclast maturation and bone resorption and colocalized with receptor-activator of nuclear-factor κ-B (RANK), the key osteoclast differentiation factor. Thus, our study shows that blocking early subchondral bone changes in OA can ameliorate articular cartilage destruction in OA.

IgSF11: the game-changer in osteoarthritis subchondral bone remodeling

Osteoarthritis (OA, a common joint disease in adults due to imbalance in cartilage formation and decay), is a complex process impacting the entire joint with no current treatments. A research team led by G.M.K and S.Y.L looked into the function of Immunoglobulin superfamily-11 (IgSF11, a protein aiding cell sticking together and osteoclast differentiation - a process creating a type of bone cell). This protein is rapidly produced in osteoclasts undergoing differentiation and in the osteoarthritic subchondral bone (bone layer beneath joint cartilage). Removing IgSF11 in mice resulted in less osteoclast activity, decreased bone thickening, and reduced cartilage breakdown in OA. The researchers believe that aiming at osteoclasts in subchondral bone could potentially treat OA effectively.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.