Human articular chondrocytes express Chemerin receptor, ChemR23, which conveys inflammatory signalling

Abstract

Common features of arthritis include destruction of extracellular matrices in cartilage and bone as a result of chronic inflammation. Cartilage deterioration is generally described as a result from the effect of immune cells and their inflammatory mediators. However, recent reports suggest a role of chondrocytes in the initiation of inflammation in joints, and that they play a pivotal role in the destruction of their own matrix. Chondrocytes express multiple immune receptors and can produce and bind several cytokines, thus rendering them possible targets for therapy. We have demonstrated that serially cultured human articular chondrocytes posses the Chemerin receptor, ChemR23, and that this receptor is also present on chondrocytes in native human cartilage. In cultured chondrocytes we detected mRNA for the Chemerin receptor, and observed that stimulation with Chemerin resulted in phosphorylation of p44/p42 MAPK and Akt. Moreover, the Chemerin stimulation resulted in a marked increase of the pro-inflammatory cytokines IL-6 and IL-8, a modest increase in TNF-α and IL-1β, and marked increase in MMP-2, MMP-3 and MMP-13 in the culture supernatants. These results show that ChemR23 conveys pro-inflammatory signalling and affects MMP production when binding its ligand Chemerin. These observations indicate that ChemR23 takes part in inflammation initiation and cartilage degradation in joint disease.