Binding of C2PS to Annexin-A1 and - A5; The possible role of C2PS in joint inflammation and mineralization

Abstract

The role of matrix vesicles (MVs) in joint development and joint inflammation has been highlighted repeatedly recently since the role of MVs in disease is being more and more explored. In young animals MVs derived of chondrocytes, containing phosphatidylserine (PS), Calcium (Ca2+) and annexins, are responsible for mineralization of cartilage resulting in linear skeletal growth. MVs contain Annexin-A5 (AnxA5) for the influx of Ca2+. In healthy, adult animals, cartilage does not mineralize. However, during osteoarthritis (OA) MVs are also present and causing mineralization of cartilage resulting in joint inflammation. In rheumatoid arthritis, MVs derived of neutrophils are present. These neutrophil derived vesicles contain Annexin-A1 (AnXA1), which function as an anti-inflammatory mediator when bound to PS during joint inflammation. Recently, a new form of PS was found in high amounts in the synovia of horses with acute synovitis. This modified form of PS has never been mentioned before and that is why we are focusing on this new, form of PS in this research. The aim of this study was to find out if this modified form of PS, C2PS, is also capable of binding to AnxA5 and AnxA1 and in this way modulate mineralization and/or inflammation. Three binding experiments were performed in vitro to answer this question. We found that AnxA1 has a binding capacity for C2PS, in contrast to AnxA5, which does not seem to bind C2PS. These new findings provide a basis for much more research in this area and it has given us an insight into the possible function of C2PS in joint inflammation of horses.