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Published on: March 18, 2019
D-chiro-inositol negatively regulates the formation of multinucleated osteoclasts by down-regulating NFATc1
Jungeun Yu1, Seunga Choi, Eui-Soon Park
1Department of Microbiology and Molecular Biology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon, 305-764, Republic of Korea.
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.
Insights
D-chiro-inositol inhibits osteoclast formation by reducing cell fusion and down-regulating NFATc1 expression. This suggests D-chiro-inositol may treat inflammatory bone loss and osteoporosis.
Area of Science:
- Biochemistry
- Cell Biology
- Bone Metabolism
Background:
- Osteoclasts (OCs) are critical for bone resorption; their accelerated activity contributes to diseases like osteoporosis.
- D-pinitol is converted to D-chiro-inositol, a potential insulin-like mediator.
- Understanding D-chiro-inositol's role in OC differentiation is crucial for bone health.
Purpose of the Study:
- To investigate the effect of D-chiro-inositol on osteoclast differentiation.
- To determine if D-chiro-inositol influences osteoclast formation and gene expression.
Main Methods:
- Osteoclastogenesis cultures were used with tartrate-resistant acid phosphatase (TRAP) staining.
- Cell fusion assays were performed with purified OC precursors.
- The impact of D-chiro-inositol on nuclear factor of activated T cells c1 (NFATc1) and OC marker gene expression was analyzed.
Main Results:
- D-chiro-inositol inhibited receptor activator of NF-κB ligand-induced OC differentiation.
- Multinucleated OC formation via cell-cell fusion was dose-dependently reduced by D-chiro-inositol.
- D-chiro-inositol suppressed osteoclastogenic gene expression by down-regulating NFATc1.
Conclusions:
- D-chiro-inositol negatively regulates osteoclastogenesis by inhibiting multinucleated OC formation.
- Down-regulation of NFATc1 by D-chiro-inositol leads to reduced OC marker gene expression.
- D-chiro-inositol shows potential as a therapeutic agent for inflammatory bone diseases and diabetic osteoporosis.
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