Mechanistic Insights into Maltol-Mediated Reversal of Postmenopausal Osteoporosis via Regulation of CDK14 Ubiquitination in Macrophages

Abstract

Maltol, primarily derived from Korean red ginseng, exhibits anti-inflammatory properties by modulating macrophage polarization and has potential therapeutic effects on postmenopausal osteoporosis, a condition linked to inflammation. This study explored the molecular mechanisms underlying maltol’s ability to inhibit M1 macrophage polarization and regulate osteoblast differentiation via macrophage-mediated pathways. Using in vitro and in vivo models, we demonstrated that maltol upregulates RNF213, which inhibits the CDK14-Pdgfrβ signaling pathway, suppressing M1 polarization and reducing NFκB phosphorylation and pro-inflammatory cytokine production. Additionally, maltol decreases TNFSF12 secretion, mitigating estrogen deficiency-induced osteoblast apoptosis and promoting differentiation. These findings highlight maltol’s potential in managing postmenopausal osteoporosis and other inflammatory diseases.