Abstract
OBJECTIVES: Osteoporosis, a prevalent metabolic bone disease affecting millions worldwide. Although MS-275 has been reported to inhibit oxidative stress, its ability to protect osteoblasts from oxidative stress damage has yet to be clarified. This study investigated whether MS-275 can inhibit oxidative stress and promote osteogenesis by activating the miRNA-200a/Keap1/Nrf2 signaling pathway. METHODS: In vitro, MC3T3-E1 cells underwent induction with carbonyl cyanide 3-chlorophenylhydrazone, leading to the establishment of an oxidative stress model, investigating the underlying mechanism. In vivo, using a rat model of ovariectomized osteoporosis, evaluating the effects of MS-275. RESULTS: In vitro, MS-275 treatment of oxidation-induced MC3T3-E1 cells resulted in up-regulation of osteoblast protein, increased expression of miRNA-200a, increased binding of miRNA-200a to Keap1 mRNA, decreased expression of Keap1 protein, and dissociation of Nrf2 from Keap1. The expressions of total Nrf2, nuclear Nrf2 and HO-1 were increased, mitochondrial function was enhanced, and oxidative damage was reduced. However, these effects were reversed after interference with miRNA-200a. In vivo,MS-275 effectively enhanced the microstructural features of distal femoral trabecular bone, increased the mineralization capacity of osteoblasts, and promoted bone formation. DISCUSSION: MS-275 can reverse oxidative stress-induced cell damage, promote bone healing, and improve osteoporosis by activating the miRNA-200a/Keap1/Nrf2 pathway.