Grit Krumbholz1, Susann Junker1, Florian M P Meier1, Markus Rickert2, Jürgen Steinmeyer3, Stefan Rehart4, Uwe Lange1, Klaus W Frommer1, Georg Schett5, Ulf Müller-Ladner1, Elena Neumann6. 1. Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany. 2. Department of Orthopaedics and Orthopaedic Surgery, University Hospital Giessen and Marburg, Giessen, Germany. 3. Laboratory for Experimental Orthopaedics, Department of Orthopaedics, Justus-Liebig-University, Giessen, Germany. 4. Department of Orthopaedics and Trauma Surgery, Agaplesion Markus-Hospital, Frankfurt, Germany. 5. Department of Medicine 3, Immunology und Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany. 6. Department of Internal Medicine and Rheumatology, Justus-Liebig-University, Giessen, and Kerckhoff-Klinik, Bad Nauheim, Germany. e.neumann@kerckhoff-klinik.de.
Abstract
OBJECTIVES: 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.
OBJECTIVES: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: G Schett; A Bozec; I Bekeredjian-Ding; H-D Chang; J-P David; T Dörner; S Grässel; M Gunzer; R Manz; H Mei; D Mielenz; U Müller-Ladner; E Neumann; A Radbruch; W Richter; R H Straub Journal: Z Rheumatol Date: 2018-05 Impact factor: 1.372