Rosavin regulates bone homeostasis through HDAC1-induced epigenetic regulation of EEF2

Bioactive constituents from Rhodiola rosea L. show a myriad of pharmacological effects on diverse diseases. Rosavin has been linked to reduced osteoclastogenesis, while its role in regulating osteogenesis remains unclear. The present study investigated whether and how Rosavin alleviates ovariectomy (OVX)-induced osteoporosis (OP) in mice. Rosavin had a therapeutic effect on OP in ovariectomized mice and inhibited osteoclast viability and promoted osteoblast viability. Integrated transcriptome sequencing, GO enrichment analysis, and PPI network construction revealed that the HDAC1/EEF2 axis was an important axis of gene action for Rosavin treatment. Mechanistically, HDAC1 suppressed EEF2 expression through histone deacetylation. Rescue experiments exhibited that HDAC1 promoted osteoclast viability, while EEF2 reversed the action of HDAC1 to restore bone homeostasis. In mice with OP, HDAC1 mitigated the effects of Rosavin, resulting in enhanced bone resorption and diminished bone formation, while EEF2 contributed to reduced bone resorption and elevated bone formation in mice. NF-κB and MAPK pathways were inhibited by Rosavin, enhanced by HDAC1, and blocked again by EEF2. To summarize, our results proved that Rosavin maintained bone homeostasis in OP via regulation of histone acetylation of EEF2, thus playing a key role as a therapeutic candidate for OP treatment.