Interleukin-1β induces differentiation of human mesenchymal stem cells into osteoblasts via the wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway

Koshiro Sonomoto, Kunihiro Yamaoka, Koichi Oshita, Shunsuke Fukuyo, Xiangmei Zhang, Kazuhisa Nakano, Yosuke Okada, Yoshiya Tanaka

研究成果: Article査読

129 被引用数 (Scopus)

抄録

Objective. Mesenchymal stem cells (MSCs) are considered to be a novel tool for the treatment of rheumatoid arthritis (RA) because of their multipotency to differentiate into osteoblasts and chondrocytes, their immunosuppressive effects, and availability. The aim of this study was to assess the mechanisms of human MSC differentiation into osteoblasts under inflammatory conditions. Methods. Human MSCs were cultured in commercialized osteogenic induction medium with inflammatory cytokines for up to 10 days. Osteoblast differentiation was detected by alkaline phosphatase staining and messenger RNA (mRNA) expression of multiple osteoblast markers. Mineralization was assessed by alizarin red S staining. Results. Among the various cytokines tested, interleukin-1β (IL-1β) induced differentiation of human MSCs into osteoblasts, which was confirmed by alkaline phosphatase activity, expression of RUNX2 mRNA, and strong alizarin red S staining. Among various molecules of the Wnt family, Wnt-5a and receptor tyrosine kinase-like orphan receptor 2 (Ror2), a major receptor of Wnt-5a, were significantly induced in human MSCs by IL-1β. Silencing of either WNT5A or ROR2 by small interfering RNA with 2 different sequences reduced alkaline phosphatase activity, RUNX2 expression, and alizarin red S staining of human MSCs induced by IL-1β. Conclusion. IL-1β effectively and rapidly induced human MSC differentiation into osteoblasts and mineralization, mainly through the noncanonical Wnt-5a/ Ror2 pathway. These results suggest potential benefits of IL-1β-treated human MSCs in the treatment of damaged bone as well as in the induction of self-renewal and self-repair of damaged tissue, including osseous tissue.

本文言語English
ページ(範囲)3355-3363
ページ数9
ジャーナルArthritis and Rheumatism
64
10
DOI
出版ステータスPublished - 2012 10月
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • リウマチ学
  • 免疫学
  • 薬理学(医学)

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