D-chiro-inositol negatively regulates the formation of multinucleated osteoclasts by down-regulating NFATc1

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Title
D-chiro-inositol negatively regulates the formation of multinucleated osteoclasts by down-regulating NFATc1
Author(s)
J Yu; S Choi; E S Park; B Shin; J Yu; S H Lee; M Takami; Jong Soon Kang; H Meong; J Rho
Bibliographic Citation
Journal of Clinical Immunology, vol. 32, no. 6, pp. 1360-1371
Publication Year
2012
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.
Keyword
D-chiro-inositolNFATc1osteoclast differentiationRANKL
ISSN
0271-9142
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s10875-012-9722-z
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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