MEDAG expression in vitro and paeoniflorin alleviates bone loss by regulating the MEDAG/AMPK/PPARγ signaling pathway .

Objectives: Osteoporosis (OP) is characterized by reduced bone mass and impaired bone microstructure. Paeoniflorin (PF) is isolated from peony root with anti-inflammatory, immunomodulatory, and bone-protective effects. Up to now, the mechanism of anti-OP in PF has not been completely clarified.

Methods: The expression of MEDAG in osteoclasts, osteoblasts and adipocytes was detected by RT-qPCR. The OVX mouse model was constructed, and oral administration of PF was performed for 15 weeks. Bone microstructure was detected by H&E staining and a micro-CT system, and expression of signaling proteins examined by Western blot and immunohistochemical staining. ELISA and biochemical kits were used to quantify serum metabolite levels.

Key Findings: MEDAG were upregulated in osteoclasts and adipocytes, and downregulated in osteoblasts. PF administration effectively alleviated OVX-induced bone loss, and histological changes in femur tissues. Moreover, PF significantly reduced serum TRAP, CTX-1, P1NP, BALP, and LDL-C levels and increased HDL-C. In addition, PF inhibited the expression of MEDAG, cathepsin K, NFATc1, PPARγ, and C/EBPα and increased -AMPKα, OPG and Runx2.

Conclusions: MEDAG is a potential target for bone diseases, and PF might attenuate OVX-induced osteoporosis via MEDAG/AMPK/PPARγ signaling pathway.