ReferenceID 2130
Isovaleric acid ameliorates ovariectomy-induced osteoporosis by inhibiting osteoclast differentiation
J Cell Mol Med
Osteoclasts (OCs) play important roles in bone remodelling and contribute to bone loss by increasing bone resorption activity. Excessively activated OCs cause diverse bone disorders including osteoporosis. Isovaleric aci
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Record Fields
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- Reference Id
- 2130
- Evidence Id
- 18720
- Core Evidence Id
- 18720
- Source Reference Id
- 4296
- Herb2 Reference Id
- HBREF005093
- Subject Paper Key
- HBIN031387_33768674
- Pubmed Id
- 33768674
- Doi
- 10.1111/jcmm.16482
- Paper Title
- Isovaleric acid ameliorates ovariectomy-induced osteoporosis by inhibiting osteoclast differentiation
- Paper Abstract
- Osteoclasts (OCs) play important roles in bone remodelling and contribute to bone loss by increasing bone resorption activity. Excessively activated OCs cause diverse bone disorders including osteoporosis. Isovaleric acid (IVA), also known as 3-methylbutanoic acid is a 5-carbon branched-chain fatty acid (BCFA), which can be generated by bacterial fermentation of a leucine-rich diet. Here, we find that IVA suppresses differentiation of bone marrow-derived macrophages into OCs by RANKL. IVA inhibited the expression of OC-related genes. IVA-induced inhibitory effects on OC generation were attenuated by pertussis toxin but not by H89, suggesting a Gi -coupled receptor-dependent but protein kinase A-independent response. Moreover, IVA stimulates AMPK phosphorylation, and treatment with an AMPK inhibitor blocks IVA-induced inhibition of OC generation. In an ovariectomized mouse model, addition of IVA to the drinking water resulted in significant decrease of body weight gain and inhibited the expression of not only OC-related genes but also fusogenic genes in the bone tissue. IVA exposure also blocked bone destruction and OC generation in the bone tissue of ovariectomized mice. Collectively, the results demonstrate that IVA is a novel bioactive BCFA that inhibits OC differentiation, suggesting that IVA can be considered a useful material to control osteoclast-associated bone disorders, including osteoporosis.
- Journal
- J Cell Mol Med
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Bone Loss; Bone Disorders; Osteoporosis
- Paper Title Cn
- Paper Title En
- Isovaleric acid ameliorates ovariectomy-induced osteoporosis by inhibiting osteoclast differentiation
- Bilingual Status
- semi_complete