Therapeutic potential of total flavonoids of Rhizoma Drynariae: inhibiting adipogenesis and promoting osteogenesis via MAPK/HIF-1α pathway in primary osteoporosis.

Abstract

This study seeks to confirm the therapeutic effectiveness of TRFD in inhibiting adipogenesis and promoting osteogenesis in primary osteoporosis through the MAPK/HIF-1α signaling pathway. C57BL/6J mice underwent ovariectomy (OVX) to induce osteoporosis. Mice were administered TRFD (Low and high doses)estradiol for a duration of 12 weeks. Bone microarchitecture evaluated using Micro-CT, while serum biomarkers and protein expressions were analyzed through enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry. Furthermore, BMSC were isolated to show differentiation, Osteogenic and adipogenic induction were performed, including ALP activity and Oil Red O staining. Bioinformatics analysis of RNA sequencing data was conducted to identify differentially expressed genes. Total flavonoids of Rhizoma Drynariae treatment significantly improved bone microarchitecture and reversed histopathological damage in OVX mice. It increased serum levels of osteogenesis markers (RUNX2, BMP-2) and enhanced MAPK and HIF-1α signaling pathways, The results also showed a significant dose, TFDR enhanced the osteogenic differentiation of BMSCs while suppressing adipogenic differentiation, as demonstrated by increased ALP activity and mineralization, alongside, the expression of lipid markers (PPAR-γ, C/EBPα) was inhibited. Furthermore, MAPK/HIF-1α pathway was confirmed be crucial in mediating these effects. TRFD exhibits significant therapeutic potential in treating primary osteoporosis by promoting osteogenesis and inhibiting adipogenesis through the MAPK/HIF-1α pathway. These establish an investigation of TRFD as a natural treatment option for managing osteoporosis. Not applicable.