Effects of yuja peel extract and its flavanones on osteopenia in ovariectomized rats and osteoblast differentiation

Scope Yuja (Citrus junos Tanaka) possesses various health benefits, but its effects on bone health are unknown. In this study, the preventative effects of yuja peel ethanol extract (YPEE) on osteopenia were determined in ovariectomized (OVX) rats, and the mechanisms by which YPEE and its flavanones regulate osteoblastogenesis were examined in vitro. Methods and results The effects of YPEE on osteoblastogenesis were investigated in MC3T3‐E1 cells. YPEE promoted alkaline phosphatase (ALP) activity, mineralization, and the expression of osteoblast differentiation marker genes, such as ALP, runt‐related transcription factor 2 (Runx2), and osteocalcin. YPEE and its flavanones promoted osteoblast differentiation via BMP‐2‐mediated p38 and the Smad1/5/8 signaling pathway. YPEE supplementation significantly decreased body weight and increased uterine weight and bone mineral density in OVX rats. Based on a micro‐CT analysis of femurs, YPEE significantly attenuated osteopenia and increased trabecular volume fraction, trabecular separation, and trabecular number (p < 0.05). Conclusion Dietary YPEE has a protective effect on OVX‐induced osteopenia. YPEE and its flavanones promote osteoblastogenesis via the activation of the BMP/p38/Smad/Runx2 pathways. These results extend our knowledge of the beneficial effects of YPEE and provide a basis for the development of novel therapies for osteoporosis. In this study, the preventative effects of yuja peel ethanol extract (YPEE) on osteopenia are determined in ovariectomized (OVX) rats, and the mechanisms by which YPEE and its flavanones regulate osteoblastogenesis are examined in vitro. YPEE supplementation significantly increases bone mineral density, trabecular volume fraction, trabecular separation, and trabecular number. YPEE and its flavanones enhance osteoblast differentiation via BMP‐2‐mediated p38 and the Smad1/5/8 signaling pathway.