alpha-MSH modulates cell adhesion and inflammatory responses of synovial fibroblasts from osteoarthritis patients

作者：Boehm Markus; Apel Mara; Lowin Torsten; Lorenz Julia; Jenei Lanzl Zsuzsa; Capellino Silvia; Dosoki Heba; Luger Thomas A; Straub Rainer H; Graessel Susanne

来源：Biochemical Pharmacology, 2016, 116: 89-99.

DOI：10.1016/j.bcp.2016.07.003

• Melanocortin receptors
• Proopiomelanocortin
• Melanocortins
• Synovium
• Synovial fibroblasts
• Osteoarthritis

Introduction: The synovium is a target for neuropeptides. Melanocortins have attained particular attention as they elicit antiinflammatory effects. Although synovial fluid from patients with rheumatic diseases contains alpha-melanocyte-stimulating hormone (alpha-MSH) it is unknown whether synovial fibroblasts generate alpha-MSH and respond to melanocortins.
Methods: Synovial tissue was obtained from osteoarthritis (OA) patients. Cells were isolated and prepared either as primary mixed synoviocytes or propagated as synovial fibroblasts (OASFs). Melanocortin receptor (MC) and proopiomelanocortin (POMC) expression were investigated by endpoint RT-PCR, immunofluorescence and Western immunoblotting. Functional coupling of MC1 was assessed by CAMP and Ca2+ assays. Cell adhesion was monitored by the xCELLigence system. Secretion of alpha-MSH, tumour necrosis factor (TNF), interleukin (IL)-6 and IL-8 was determined by ELISA.
Results: OASFs in vitro expressed MC1. MC1 transcripts were present in synovial tissue and appropriate immunoreactivity was detected in synovial fibroblasts in situ. OASFs contained truncated POMC transcripts but neither full-length POMC mRNA, POMC protein nor alpha-MSH were detectable. In accordance with this only truncated POMC transcripts were present in synovial tissue. alpha-MSH increased cAMP dose-dependently but did not alter calcium in OASFs. alpha-MSH also enhanced adhesion of OASFs to fibronectin and reduced TNF, IL-6 and IL-8 secretion in primary mixed synoviocyte cultures. In OASFs, alpha-MSH modulated basal and TNF/IL-1 beta-mediated secretion of IL-6 and IL-8.
Conclusion: Synovial fibroblasts express MC1 in vitro and in situ. alpha-MSH elicits biological effects in these cells suggesting an endogenous immunomodulatory role of melanocortins within the synovium. Our results encourage in vivo studies with melanocortins in OA models.

• 出版日期2016-9-15