Cardamonin attenuates osteoporosis progression and promotes osteogenic differentiation of bone mesenchymal stem cells by upregulating TCF4 expression.

Abstract

BACKGROUND: Osteoporosis is a common skeletal metabolic disorder. Cardamonin (CAR) is a natural chalcone compound with multiple activities. However, the role and mechanism of CAR in osteoporosis progression remain largely unknown. METHODS: Mice underwent ovariectomy (OVX) to establish a model of osteoporosis, and bone loss was analyzed. Osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) was induced by culturing in osteoblast medium, and evaluated by determining ALP, OCN, RUNX2, and OSX levels using qRT-PCR and western blotting. Bioinformatics analysis was conducted using the SEA server, DisGeNet database, and GSE35959 GEO dataset. TCF4 protein expression was examined using western blotting. RESULTS: CAR mitigated OVX-induced bone loss in mice and promoted osteogenic differentiation of hBMSCs by increasing the expression levels of ALP, OCN, RUNX2, and OSX. TCF4 expression was reduced in osteoporosis, and CAR upregulated TCF4 level. TCF4 overexpression promoted osteogenic differentiation of hBMSCs, while its silencing weakened the promoting effect of CAR on osteogenic differentiation. CONCLUSION: CAR attenuates bone loss in an OVX-induced mouse model of osteoporosis and promotes osteogenic differentiation of hBMSCs via increasing TCF4 expression, indicating the therapeutic potential of CAR in osteoporosis.