title: α-MSH modulates cell adhesion and inflammatory responses of synovial fibroblasts from osteoarthritis patients.
abstract: 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 α-melanocyte-stimulating hormone (α-MSH) it is unknown whether synovial fibroblasts generate α-MSH and respond to melanocortins.
  
  
  
  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 Ca(2+) assays. Cell adhesion was monitored by the xCELLigence system. Secretion of α-MSH, tumour necrosis factor (TNF), interleukin (IL)-6 and IL-8 was determined by ELISA.
  
  
  
  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 α-MSH were detectable. In accordance with this only truncated POMC transcripts were present in synovial tissue. α-MSH increased cAMP dose-dependently but did not alter calcium in OASFs. α-MSH also enhanced adhesion of OASFs to fibronectin and reduced TNF, IL-6 and IL-8 secretion in primary mixed synoviocyte cultures. In OASFs, α-MSH modulated basal and TNF/IL-1β-mediated secretion of IL-6 and IL-8.
  
  
  
  Synovial fibroblasts express MC1in vitro and in situ. α-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.
authors.affiliation: Dept. of Dermatology, Laboratory for Neuroendocrinology and Interdisciplinary Endocrinology, University of Münster, Münster, Germany. Electronic address: bohmm@uni-muenster.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Böhm
authors.affiliation: Dept. of Dermatology, Laboratory for Neuroendocrinology and Interdisciplinary Endocrinology, University of Münster, Münster, Germany. Electronic address: wachsmut@uni-muenster.de.
authors.forename: Mara
authors.initials: M
authors.lastname: Apel
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Dept. of Internal Medicine I, University of Regensburg, Regensburg, Germany. Electronic address: torsten.lowin@googlemail.com.
authors.forename: Torsten
authors.initials: T
authors.lastname: Lowin
authors.affiliation: Dept. of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany; Centre for Medical Biotechnology, BioPark I, Regensburg, Germany. Electronic address: Julia2.Lorenz@klinik.uni-regensburg.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Lorenz
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Dept. of Internal Medicine I, University of Regensburg, Regensburg, Germany. Electronic address: zsuzsa.jenei-lanzl@ukr.de.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Jenei-Lanzl
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Dept. of Internal Medicine I, University of Regensburg, Regensburg, Germany. Electronic address: s.capellino@kerckhoff-klinik.de.
authors.forename: Silvia
authors.initials: S
authors.lastname: Capellino
authors.affiliation: Dept. of Dermatology, Laboratory for Neuroendocrinology and Interdisciplinary Endocrinology, University of Münster, Münster, Germany. Electronic address: hebasalah40@gmail.com.
authors.forename: Heba
authors.initials: H
authors.lastname: Dosoki
authors.affiliation: Dept. of Dermatology, Laboratory for Neuroendocrinology and Interdisciplinary Endocrinology, University of Münster, Münster, Germany. Electronic address: Thomas.Luger@ukmuenster.de.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Dept. of Internal Medicine I, University of Regensburg, Regensburg, Germany. Electronic address: rainer.straub@klinik.uni-regensburg.de.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.affiliation: Dept. of Orthopaedic Surgery, University of Regensburg, Regensburg, Germany; Centre for Medical Biotechnology, BioPark I, Regensburg, Germany. Electronic address: Susanne.Graessel@klinik.uni-regensburg.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Grässel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000819:agonists / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013582:Synovial Fluid; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000070918:Synoviocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005353:Fibronectins; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000242:Cyclic AMP
keywords: Melanocortin receptors; Melanocortins; Osteoarthritis; Proopiomelanocortin; Synovial fibroblasts; Synovium