Synovial fibroblasts are novel target cells for the melanocortin peptide α-melanocyte-stimulating hormone

Abstract

There is increasing evidence that the proopiomelanocortin (POMC) system plays an important role in the osteoarticular system (Böhm and Grässel, Endocr. Rev. 2012). However, whether synovial fibroblasts express receptors for α-melanocyte-stimulating hormone (α-MSH) and/or generate proopiomelanocortin (POMC)-derived peptides is unknown. We show that synovial fibroblasts from OA patients express melanocortin-1 receptor (MC1R) on the RNA and protein level in vitro . MC1R immunoreactivity is also detectable in fibroblasts of synovial tissue in situ as shown by immunofluorescence analysis. The detected MC1R in synovial fibroblasts is weakly coupled to adenylate cyclase as demonstrated by increased intracellular cAMP but not Ca 2 levels after α-MSH treatment. Notably, α-MSH significantly reduced IL-1β-mediated secretion of IL-8 in half of the donors ( n = 6) while in the others it had no effect. Furthermore, although truncated POMC transcripts are present in cultured synovial fibroblasts from OA patients, these cells neither expressed full-length POMC mRNA, POMC protein, nor secreted detectable α-MSH amounts into the culture media, ruling out an autocrine loop for melanocortin peptides. Our findings highlight synovial fibroblasts as a novel target cell type for melanocortins within the osteoarticular system and encourage further exploitation of such peptides for the treatment of inflammatory and/or degenerative joint diseases.