Inhibition of interleukin‐6 receptor directly blocks osteoclast formation in vitro and in vivo
Open Access
- 27 August 2009
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 60 (9), 2747-2756
- https://doi.org/10.1002/art.24781
Abstract
Objective To investigate the efficacy of a murine anti–interleukin-6 receptor (anti–IL-6R) antibody in directly blocking tumor necrosis factor (TNF)– and RANKL-mediated osteoclastogenesis in vitro and in vivo. Methods The efficacy of a murine antibody against IL-6R in blocking osteoclast differentiation of mononuclear cells stimulated with RANKL was tested. In addition, arthritic human TNFα–transgenic mice were treated with anti–IL-6R antibody, and osteoclast formation and bone erosion were assessed in arthritic paws. Results Blockade of IL-6R dose dependently reduced osteoclast differentiation and bone resorption in monocyte cultures stimulated with RANKL or RANKL plus TNF. In human TNFα–transgenic mice, IL-6R blockade did not inhibit joint inflammation, but it strongly reduced osteoclast formation in inflamed joints as well as bone erosion in vivo. Neither the cell influx into joints nor the synovial expression of IL-6 and RANKL changed with IL-6R blockade, while the synovial expression of IL-1 was significantly reduced. In contrast, TNF-mediated systemic bone loss was not inhibited by IL-6R blockade. Conclusion These data suggest that blockade of IL-6R directly affects osteoclast formation in vitro and in vivo, suggesting a direct and specific effect of anti–IL-6R therapy on osteoclasts independently of its antiinflammatory effects. This effect adds significantly to the structure-sparing potential of pharmacologic blockade of IL-6R in arthritis.Keywords
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