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

Research output: Contribution to journalArticle

46 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
Externally publishedYes

Fingerprint

Osteoprotegerin
Mesenchymal Stromal Cells
Osteogenesis
Osteoclasts
Rheumatoid Arthritis
Cathepsin K
NFATC Transcription Factors
Conditioned Culture Medium
Anti-Idiotypic Antibodies
Differentiation Antigens
Immunosuppressive Agents
Dendritic Cells
Small Interfering RNA
Cultured Cells
Blood Cells
Joints
Lymphocytes
Staining and Labeling
Bone and Bones

ASJC Scopus subject areas

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

Cite this

Oshita, K., Yamaoka, K., Udagawa, N., Fukuyo, S., Sonomoto, K., Maeshima, 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

Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. / Oshita, Koichi; Yamaoka, Kunihiro; Udagawa, Nobuyuki; Fukuyo, Shunsuke; Sonomoto, Koshiro; Maeshima, Keisuke; Kurihara, Ryuji; Nakano, Kazuhisa; Saito, Kazuyoshi; Okada, Yosuke; Chiba, Kenji; Tanaka, Yoshiya.

In: Arthritis and Rheumatism, Vol. 63, No. 6, 06.2011, p. 1658-1667.

Research output: Contribution to journalArticle

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, vol. 63, no. 6, pp. 1658-1667. https://doi.org/10.1002/art.30309
Oshita K, Yamaoka K, Udagawa N, Fukuyo S, Sonomoto K, Maeshima K et al. Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. Arthritis and Rheumatism. 2011 Jun;63(6):1658-1667. https://doi.org/10.1002/art.30309
Oshita, Koichi ; Yamaoka, Kunihiro ; Udagawa, Nobuyuki ; Fukuyo, Shunsuke ; Sonomoto, Koshiro ; Maeshima, Keisuke ; Kurihara, Ryuji ; Nakano, Kazuhisa ; Saito, Kazuyoshi ; Okada, Yosuke ; Chiba, Kenji ; Tanaka, Yoshiya. / Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 6. pp. 1658-1667.
@article{f4207898778f4fb39d91e4b22f16fba5,
title = "Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production",
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.",
author = "Koichi Oshita and Kunihiro Yamaoka and Nobuyuki Udagawa and Shunsuke Fukuyo and Koshiro Sonomoto and Keisuke Maeshima and Ryuji Kurihara and Kazuhisa Nakano and Kazuyoshi Saito and Yosuke Okada and Kenji Chiba and Yoshiya Tanaka",
year = "2011",
month = "6",
doi = "10.1002/art.30309",
language = "English",
volume = "63",
pages = "1658--1667",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - Human mesenchymal stem cells inhibit osteoclastogenesis through osteoprotegerin production

AU - Oshita, Koichi

AU - Yamaoka, Kunihiro

AU - Udagawa, Nobuyuki

AU - Fukuyo, Shunsuke

AU - Sonomoto, Koshiro

AU - Maeshima, Keisuke

AU - Kurihara, Ryuji

AU - Nakano, Kazuhisa

AU - Saito, Kazuyoshi

AU - Okada, Yosuke

AU - Chiba, Kenji

AU - Tanaka, Yoshiya

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79958062208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958062208&partnerID=8YFLogxK

U2 - 10.1002/art.30309

DO - 10.1002/art.30309

M3 - Article

C2 - 21360521

AN - SCOPUS:79958062208

VL - 63

SP - 1658

EP - 1667

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 6

ER -