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

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50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1658-1667
Number of pages10
JournalArthritis and Rheumatism
Volume63
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Oshita, K., Yamaoka, K., Udagawa, N., Fukuyo, S., Sonomoto, K., Maeshima, K., Kurihara, R., Nakano, K., Saito, K., Okada, Y., Chiba, K., & Tanaka, Y. (2011). Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. Arthritis and Rheumatism, 63(6), 1658-1667. https://doi.org/10.1002/art.30309