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

Abstract

ObjectivesOsteoporosis (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. MethodsThe 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 findingsMEDAG 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 p-AMPKα, OPG and Runx2. ConclusionsMEDAG is a potential target for bone diseases, and PF might attenuate OVX-induced osteoporosis via MEDAG/AMPK/PPARγ signaling pathway.