Page 28 - G. Cell differentiation. division. and death

[G. Cell differentiation, division, and death-19]

A branched-chain fatty acid ameliorates ovariectomy-induced

osteoporosis by inhibiting osteoclast differentiation

Kwang Min Cho¹, Ye Seon Kim¹, Mingyu Lee², Ha Young Lee¹, Yoe-Sik Bae¹˙²˙*

¹Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea, ²Health Sciences and Technology,

SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea

Branched-chain fatty acids (BCFAs), are produced by bacterial fermentation of leucine rich food. In this study, we
discovered that a BCFA stimulates bone marrow-derived macrophages (BMDMs) chemotactic migration and

suppressed RANKL-induced OC differentiation. As a result, the BCFA inhibited the expression of OC-related genes.

The BCFA-induced inhibitory effects on OC generation was blocked by pertussis toxin (PTX) but not by protein
kinase A (PKA) inhibitor H89, suggesting that Gi-coupled receptor-dependent but PKA-independent response.
Furthermore, the BCFA stimulates AMPK phosphorylation, besides the BCFA-induced inhibition of OC generation

was blocked by AMPK inhibitor. In an ovariectomized mouse model, the group that drank water containing the
BCFA significantly recovered body weight loss and decreased the expression of OC-related genes and fusogenic

genes in total bone tissue. The BCFA also blocked bone density and OC generation in bone tissue of ovariectomized
mice. Taken together, we discovered that the BCFA is a novel metabolite that inhibits OC differentiation, suggesting

that the BCFA can be considered as a useful material for the development of therapeutic agents to control
osteoclast-associated bone disorders such as osteoporosis.