Resveratrol promotes osteogenic differentiation of bone marrow mesenchymal stem cells in an inflammatory microenvironment

Zou Yulian; Chen Chaopei; Huang Haixia; Lan Yuyan; Liu Min; Huang Ting

doi:10.12307/2026.057

Abstract：BACKGROUND:The incidence of peri-implantitis is increasing in China,which greatly affects restorative results of implants.To explore whether resveratrol can improve the biological activity and mechanism of bone marrow mesenchymal stem cells in inflammatory microenvironment can provide some theoretical support for the development of therapeutic drugs related to peri-implantitis. OBJECTIVE:To investigate the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells in an inflammatory microenvironment. METHODS:Bone marrow mesenchymal stem cells were extracted and purified from SD rats by whole bone marrow apposition method.Bone marrow mesenchymal stem cells were divided into three groups as follows:normal control group,lipopolysaccharide group(1 μg/mL),lipopolysaccharide+resveratrol(1 μmol/L)group,and received the intervention for 24 hours.DCFH-DA reactive oxygen species fluorescent probe was used to detect reactive oxygen species levels.RT-qPCR was used to detect the mRNA expression of pro-inflammatory genes interleukin-1β,interleukin-18,and tumor necrosis factor-α.Alkaline phosphatase staining was performed 7 days after osteogenic induction.Alizarin red staining was performed 21 days after osteogenic induction.RT-qPCR was used to detect the mRNA expression of osteogenic genes Runx2 and Osx 7 days after osteogenic induction.Western blot assay was used to detect the protein expression of FoxO1 and NLRP3 7 days after osteogenic induction. RESULTS AND CONCLUSION:(1)Resveratrol alleviated the inhibitory effect of the inflammatory microenvironment on alkaline phosphatase activity and calcified nodule formation in bone marrow mesenchymal stem cells.(2)Resveratrol inhibited mRNA expression of pro-inflammatory genes interleukin-1β,interleukin-18,and tumor necrosis factor-α and up-regulated mRNA expression of osteogenic genes Runx2 and Osx in bone marrow mesenchymal stem cells in the inflammatory microenvironment.(3)Resveratrol downregulated reactive oxygen species levels in bone marrow mesenchymal stem cells in the inflammatory microenvironment.(4)Resveratrol promoted FoxO1 protein expression and inhibited NLRP3 protein expression.(5)The results confirm that resveratrol(1 μmol/L)activates the FoxO1 signaling pathway and inhibits the expression of NLRP3 inflammatory vesicles,which reduces the release of inflammatory factors,removes excessive reactive oxygen species,and ultimately promotes the osteogenic differentiation of bone marrow mesenchymal stem cells in the inflammatory microenvironment.