title: Response of human rheumatoid arthritis osteoblasts and osteoclasts to adiponectin.
abstract: OBJECTIVE
  Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated.
  
  
  METHODS
  Adiponectin and its receptors were examined in bone tissue. Primary human osteoblasts and osteoclasts were stimulated with adiponectin and analysed using realtime polymerase chain-reaction and immunoassays. Effects on matrix-production by osteoblasts and differentiation and resorptive activity of osteoclasts were examined.
  
  
  RESULTS
  Immunohistochemistry of rheumatoid arthritis bone tissue showed adiponectin expression in key cells of bone remodelling. Adiponectin altered gene expression and cytokine release in osteoblasts and increased IL-8 secretion by osteoclasts. Adiponectin inhibited osterix and induced osteoprotegerin mRNA in osteoblasts. In osteoclasts, MMP-9 and tartrate resistant acid phosphatase expression was increased. Accordingly, mineralisation capacity of osteoblasts decreased whereas resorptive activity of osteoclasts increased.
  
  
  CONCLUSIONS
  The results confirm the proinflammatory potential of adiponectin and support the idea that adiponectin influences rheumatoid arthritis bone remodelling through alterations in osteoblast and osteoclast.
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Grit
authors.initials: G
authors.lastname: Krumbholz
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Junker
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Florian M P
authors.initials: FMP
authors.lastname: Meier
authors.affiliation: Department of Orthopaedics and Orthopaedic Surgery, University Hospital Giessen and Marburg, Giessen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rickert
authors.affiliation: Laboratory for Experimental Orthopaedics, Department of Orthopaedics, Justus-Liebig-University, Giessen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Steinmeyer
authors.affiliation: Department of Orthopaedics and Trauma Surgery, Agaplesion Markus-Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rehart
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lange
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Frommer
authors.affiliation: Department of Medicine 3, Immunology und Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany. e.neumann@kerckhoff-klinik.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D000071681:Tartrate-Resistant Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D053244:Osteoprotegerin; D054419:Receptors, Adiponectin; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; C506030:TNFRSF11B protein, human; D014157:Transcription Factors; D000071681:Tartrate-Resistant Acid Phosphatase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9