Pathological role of osteoclast costimulation in arthritis-induced bone loss

Sae Ochi, Masahiro Shinohara, Kojiro Sato, Hans Jürgen Gober, Takako Koga, Tatsuhiko Kodama, Toshiyuki Takai, Nobuyuki Miyasaka, Hiroshi Takayanagi

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


Abnormal T cell immune responses induce aberrant expression of inflammatory cytokines such as TNF-α, leading to osteoclast-mediated bone erosion and osteoporosis in autoimmune arthritis. However, the mechanism underlying enhanced osteoclastogenesis in arthritis is not completely understood. Here we show that TNF-α contributes to inflammatory bone loss by enhancing the osteoclastogenic potential of osteoclast precursor cells through inducing paired Ig-like receptor-A (PIR-A), a costimulatory receptor for receptor activator of NF-κB (RANK). In fact, bone erosion and osteoporosis, but not inflammation, caused by aberrant TNF-α expression were ameliorated in mice deficient in Fc receptor common γ subunit or β2- microglobulin, in which the expression of PIR-As and PIR-A ligands is impaired, respectively. These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases.

Original languageEnglish
Pages (from-to)11394-11399
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
Publication statusPublished - 2007 Jul 3


  • Costimulatory
  • Paired immunoglobulin-like receptor
  • Rheumatoid arthritis
  • TNF-α


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