Skip to main content
  • Poster presentation
  • Open access
  • Published:

STAT3 is critical to promote inflammatory cytokines and RANKL expression in inflammatory arthritis

Rheumatoid arthritis (RA) causes sever joint damage and significant disability of daily living. The symptoms of RA patients are mainly from chronic inflammation and continuous joint destruction, however, the mechanisms underlying how inflammation and joint destruction in RA develop and are sustained chronically remain largely unclear. In this study, we show that signal transducer and activator of transcription 3 (STAT3) plays a critical role in both chronic inflammation and joint destruction in RA. We found that inflammatory cytokines, such as IL-1β, TNFα and IL-6, activated STAT3 either directly or indirectly and induced expression of inflammatory cytokines, further activating STAT3. STAT3 activation also induced expression of receptor activator of nuclear factor kappa B ligand (RANKL), an essential cytokine for osteoclast differentiation. STAT3 knockout or pharmacological inhibition resulted in significant reduction of the expression of both inflammatory cytokines and RANKL in vitro. STAT3 inhibition was also effective in treating an RA model, collagen induced arthritis (CIA), in vivo through significant reduction in expression of inflammatory cytokines and RANKL, inhibiting both inflammation and joint destruction. Thus our data provide new insight into pathogenesis of RA and provide evidence that inflammatory cytokines induce a cytokine amplification loop via STAT3 that promotes sustained inflammation and joint destruction.

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Miyamoto, T., Mori, T., Yoshimura, A. et al. STAT3 is critical to promote inflammatory cytokines and RANKL expression in inflammatory arthritis. Arthritis Res Ther 14 (Suppl 1), P43 (2012).

Download citation

  • Published:

  • DOI: