論文

査読有り 国際誌
2020年9月24日

TSLP is a negative regulator of RANKL-induced osteoclastogenesis.

Biochemical and biophysical research communications
  • Tatsukuni Ohno
  • ,
  • Takashi Nakamura
  • ,
  • Susumu Nakae
  • ,
  • Hideaki Morita
  • ,
  • Kenji Matsumoto
  • ,
  • Hirohisa Saito
  • ,
  • Kazuyoshi Takeda
  • ,
  • Ko Okumura
  • ,
  • Toshifumi Azuma

530
3
開始ページ
508
終了ページ
512
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2020.05.055

Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family, which is known to activate type 2 innate lymphoid cells, mast cells, and Th2 cells; this activation results in allergic inflammation and host defense against parasites. TSLP has also been shown to promote Th17-mediated immune responses, such as those observed in the development of rheumatoid arthritis; however, its role in osteoclastogenesis remains poorly understood. Here, we investigated the functional involvement of TSLP in RANKL-induced osteoclast differentiation from murine bone marrow-derived macrophages (BMMs). Both RANK- and RANK+ macrophages expressed TSLP receptor (TSLPR), while RANK+ osteoclast precursors maintained TSLPR expression after RANKL stimulation. TSLP stimulation led to inhibition of RANK-induced osteoclast differentiation in wild-type BMMs, but not Tslpr-/- BMMs; TSLP stimulation also led to suppression of osteoclastogenic gene expression (Nfatc1, Acp5, Mmp9, and Ctsk). These inhibitory effects of TSLP were significantly reduced following STAT1 inhibition. Finally, we found that LPS stimulation induced TSLP production in murine calvarial osteoblasts, but not BMMs. Together, these observations suggest that TSLP acts directly on osteoclast precursors to suppress osteoclastogenesis. Osteoblasts, along with other TSLP-producing cells, may therefore contribute to the inhibition of osteoclastogenesis under inflammatory conditions.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2020.05.055
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32600615

エクスポート
BibTeX RIS