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Updated: Jul 15, 2026
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Published on: July 26, 2022
miR-329-3p in Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Promotes Bone Regeneration in Diabetic Fractures by
Teng Ma1, Mochi Yang2, Xiaoli Zhou3
1Department of Traumatic Orthopedics, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China, nxmu.edu.cn.
Purpose:
Influence of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) on fracture healing in diabetes mellitus (DM) was investigated.
Methods:
Serum LSD1, SIRT3, superoxide dismutase (SOD), and malondialdehyde (MDA) were detected in patients with diabetic fractures. Under high-glucose (HG) conditions, influences of LSD1, SIRT3, BMSCs-derived Exo, and BMSCs-derived Exo harboring miR-329-3p on osteogenic differentiation and oxidative stress of MC3T3-E1 cells were assayed via ALP staining, western blotting, dichlorofluorescin diacetate (DCFH-DA) staining, and enzyme-linked immunosorbent assay (ELISA). Mice with diabetic fractures were treated by BMSCs, BMSCs-derived Exo, or a combination of BMSCs and GW4869. Western blotting and immunohistochemistry examined protein expression in fracture tissues.
Results:
DM patients with nonunion showed higher serum LSD1 and MDA and lower serum SIRT3 and SOD than those with normal fracture healing. In HG-induced MC3T3-E1 cells, LSD1 silencing upregulated SIRT3, RUNX2, OPG, and SOD, increased mature osteoblasts, and reduced reactive oxygen species (ROS) and MDA; SIRT3 silencing revered these results. LSD1 downregulated SIRT3, RUNX2, OPG, and SOD, reduced mature osteoblasts, and enhanced ROS and MDA in HG-induced MC3T3-E1 cells; BMSCs-derived Exo abrogated these influences. BMSCs-derived Exo harboring miR-329-3p suppressed LSD1 and ROS, upregulated SIRT3, RUNX2, and OPG, and increased mature osteoblasts in HG-induced MC3T3-E1 cells. BMSCs transplantation in diabetic fracture mice elevated SIRT3, ALP, RUNX2, OPG, and miR-329-3p and reduced LSD1 in fracture tissues; miR-329-3p silencing in BMSCs or GW4869 treatment of mice counteracted these effects.
Conclusion:
BMSCs-derived Exo harboring miR-329-3p induces bone regeneration in diabetic fractures by relieving the SIRT3-mediated oxidative stress via inhibiting LSD1. It has potential in treating diabetic fractures.
