Many recent studies have suggested that
bergapten (BP), a class of native compound with numerous
biological activities such as anti-resorptive properties, may exert protective effects against
postmenopausal bone loss. However, it remains unknown whether BP regulates or improves the osteogenic function of bone marrow stromal cells (BMSCs) in the treatment and prevention of
osteoporosis. In our study, BMSCs were cultured in osteogenic induction medium with the addition of BP for 2 weeks and an ovariectomized mouse model of
osteoporosis was used to investigate the anti-resorptive effect of BP by gavage administration for 3 months. The concentrations of BP used were 0.1, 1, and 10 μmol/L in vitro and the gavage dose was 20 mg/kg/d. The result of our study indicated that BP promotes the expression of
alkaline phosphatase (ALP) by BMSCs in vitro in a dose-dependent manner, as revealed by ALP staining. Runt-related
transcription factor 2 and
osteocalcin were up-regulated both in vitro and vivo, while osterix and
collagen Iα1, assessed by immunofluorescence and immunohistochemistry, were correspondingly raised in the presence of BP in BMSCs in vitro. In addition, a protective effect of BP against
ovariectomy-induced bone loss was found by distal femur micro-CT scanning, with improvements of bone metabolism parameters such as bone mineral density, trabecular number, and trabecular separation. Furthermore, WNT/β-
catenin signaling was activated in the presence of BP in BMSCs in osteogenic culture. Finally, BP promoted differentiation of BMSCs into osteoblasts by up-regulation of the WNT/β-
catenin pathway.