Mesenchymal Stem Cells Prevent Ovariectomy-Induced Osteoporosis Formation in Mice by Intraosseous Vascular Remodeling

Abstract

BackgroundPostmenopausal osteoporosis is the most common type of primary osteoporosis that is characterized by a decrease in bone mass and an increase risk of fractures. Mesenchymal stem cells (MSCs) can promote osteogenesis and are a promising therapy for postmenopausal osteoporosis. The aim of this study was to clarify the relationship between improved intraosseous microcirculation and increased bone mass by MSCs in postmenopausal osteoporosis.MethodsWe isolated primary MSCs and characterized their cellular properties. Bone volume and morphological analyses of mouse femurs were performed by transplanting the cells into post-ovariectomized mice via tail vein. Femoral artery ligation was performed on mice. By Laser Speckle flowmetry, vascular perfusion and femoral trabecular bone and cortical bone analysis, we determined the effects of MSCs in promoting intraosseous angiogenesis and preventing osteoporosis in mice. ResultsMSCs transplantation enhanced trabecular number, trabecular bone volume / total volume, and trabecular bone mineral density in ovariectomized mice. Reduced intraosseous blood flow due to hindlimb ischemia can lead to accelerated bone loss. In contrast, MSCs promoted the reconstruction of intraosseous microcirculation and reduced bone loss.ConclusionsMSCs could effectively prevent postmenopausal osteoporosis formation, which is associated with the involvement of MSCs in the reestablishment of microcirculation within the skeleton. This study has revealed the potential role of MSCs in the treatment of postmenopausal osteoporosis and lays the foundation for clinical application studies.