Publications (2)4.27 Total impact
Article: Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin(21-157).[show abstract] [hide abstract]
ABSTRACT: Chemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators. Tissue sections were taken from human knee joints and labelled with antibodies towards chemerin and ChemR23. Chondrocytes from cartilage tissue were isolated, cultured and assessed for chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation and intracellular signalling were studied by assessment of phosphorylated mitogen activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells with recombinant chemerin(21-157). Biological effects of chemerin(21-157) were investigated by measuring secretion of pro-inflammatory cytokines and metalloproteases in cell supernatants. Both serially cultured human articular chondrocytes and resident cells in native cartilage expressed chemerin and ChemR23. Stimulating cells with chemerin(21-157) resulted in phosphorylation of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and the matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected. These results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin. Chemerin(21-157) stimulation engaged signal-transduction pathways that further promoted inflammatory signalling in chondrocytes, as judged by an enhanced secretion of cytokines and metalloproteases. Taken together, the previously reported chemotaxis and the present findings suggest that the receptor and its ligand may play pivotal roles in joint inflammation.Arthritis research & therapy 12/2010; 12(6):R228. · 4.27 Impact Factor
Article: Human articular chondrocytes express Chemerin receptor, ChemR23, which conveys inflammatory signalling[show abstract] [hide abstract]
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.