Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production

Koichi Oshita, Kunihiro Yamaoka, Nobuyuki Udagawa, Shunsuke Fukuyo, Koshiro Sonomoto, Keisuke Maeshima, Ryuji Kurihara, Kazuhisa Nakano, Kazuyoshi Saito, Yosuke Okada, Kenji Chiba, Yoshiya Tanaka

研究成果: Article査読

59 被引用数 (Scopus)

抄録

Objective Mesenchymal stem cells (MSCs) have been proposed to be a useful tool for treatment of rheumatoid arthritis (RA), not only because of their multipotency but also because of their immunosuppressive effect on lymphocytes, dendritic cells, and other proinflammatory cells. Since bone destruction caused by activated osteoclasts occurs in RA, we undertook the present study to investigate the effect of MSCs on osteoclast function and differentiation in order to evaluate their potential use in RA therapy. Methods Human MSCs and peripheral blood mononuclear cells were cultured under cell-cell contact-free conditions with osteoclast induction medium. Differentiation into osteoclast-like cells was determined by tartrate-resistant acid phosphatase staining and expression of osteoclast differentiation markers. Results The number of osteoclast-like cells was decreased and expression of cathepsin K and nuclear factor of activated T cells c1 (NF-ATc1) was down-regulated by the addition of either MSCs or a conditioned medium obtained from MSCs. Osteoprotegerin (OPG) was constitutively produced by MSCs and inhibited osteoclastogenesis. However, osteoclast differentiation was not fully recovered upon treatment with either anti-OPG antibody or OPG small interfering RNA, suggesting that OPG had only a partial role in the inhibitory effect of MSCs. Moreover, bone-resorbing activity of osteoclast-like cells was partially recovered by addition of anti-OPG antibody into the conditioned medium. Conclusion The present results indicate that human MSCs constitutively produce OPG, resulting in inhibition of osteoclastogenesis and expression of NF-ATc1 and cathepsin K in the absence of cell-cell contact. Therefore, we conclude that human MSCs exert a suppressive effect on osteoclastogenesis, which may be beneficial in inhibition of joint damage in RA.

本文言語English
ページ(範囲)1658-1667
ページ数10
ジャーナルArthritis and Rheumatism
63
6
DOI
出版ステータスPublished - 2011 6

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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