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Journal of Clinical Immunology

, Volume 32, Issue 6, pp 1360–1371 | Cite as

D-chiro-inositol Negatively Regulates the Formation of Multinucleated Osteoclasts by Down-Regulating NFATc1

  • Jungeun Yu
  • Seunga Choi
  • Eui-Soon Park
  • Bongjin Shin
  • Jiyeon Yu
  • Seoung Hoon Lee
  • Masamichi Takami
  • Jong Soon Kang
  • Hyungun Meong
  • Jaerang RhoEmail author
Article

Abstract

Purpose

Osteoclasts (OCs) are multinucleated giant cells that resorb bone matrix. Accelerated bone destruction by OCs might cause several metabolic bone-related diseases, such as osteoporosis and inflammatory bone loss. D-pinitol (3-O-methyl-D-chiro-inositol) is a prominent component of dietary legumes and is actively converted to D-chiro-inositol, which is a putative insulin-like mediator. In this study, we analyzed the effect of D-chiro-inositol on OC differentiation.

Methods

To analyze the role of D-chiro-inositol on OC differentiation, we examined OC differentiation by the three types of osteoclastogenesis cultures with tartrate-resistant acid phosphatase (TRAP) staining and solution assay. Then, we carried out cell fusion assay with purified TRAP+ mononuclear OC precursors. Finally, we analyzed the effect of D-chiro-inositol on OC maker expression in response to the regulation of nuclear factor of activated T cells c1 (NFATc1).

Results

We demonstrated that D-chiro-inositol acts as an inhibitor of receptor activator of NF-κB ligand-induced OC differentiation. The formation of multinucleated OCs by cell-cell fusion is reduced by treatment with D-chiro-inositol in a dose-dependent manner. In addition, we demonstrated that D-chiro-inositol inhibits the expression of several osteoclastogenic genes by down-regulating NFATc1.

Conclusions

We have shown that D-chiro-inositol is negatively involved in osteoclastogenesis through the inhibition of multinucleated OC formation by cell-cell fusion. The expression of NFATc1 was significantly down-regulated by D-chiro-inositol in OCs and consequently, the expression of OC marker genes was significantly reduced. Hence, these results show that D-chiro-inositol might be a good candidate to treat inflammatory bone-related diseases or secondary osteoporosis in diabetes mellitus.

Keywords

D-chiro-inositol RANKL NFATc1 osteoclast differentiation 

Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-2009-0072758 & NRF-2009-008146) and the Ministry of National Defense Foundation Grant (ADD: 08-10-02).

Conflict of Interest

All authors have no financial conflicts of interest.

Supplementary material

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ESM 1 (DOCX 29 kb)
10875_2012_9722_MOESM2_ESM.pptx (746 kb)
Supplemental Figure 1 (PPTX 745 kb)
10875_2012_9722_MOESM3_ESM.pptx (53 kb)
Supplemental Figure 2 (PPTX 52 kb)
10875_2012_9722_MOESM4_ESM.pptx (113 kb)
Supplemental Figure 3 (PPTX 112 kb)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Jungeun Yu
    • 1
  • Seunga Choi
    • 1
  • Eui-Soon Park
    • 1
  • Bongjin Shin
    • 1
  • Jiyeon Yu
    • 1
  • Seoung Hoon Lee
    • 2
  • Masamichi Takami
    • 3
  • Jong Soon Kang
    • 4
  • Hyungun Meong
    • 5
  • Jaerang Rho
    • 1
    Email author
  1. 1.Department of Microbiology and Molecular BiologyChungnam National UniversityDaejeonRepublic of Korea
  2. 2.Department of Oral Microbiology and ImmunologyWonkwang University School of DentistryIksanRepublic of Korea
  3. 3.Department of Biochemistry, School of DentistryShowa UniversityShinagawakuJapan
  4. 4.Korea Research Institute of Bioscience and BiotechnologyChungcheongbuk-doRepublic of Korea
  5. 5.Institute of Molecular GeneticsDaejeonRepublic of Korea

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