Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Protect Bone against Ovariectomy‑Induced Osteoporosis through ERK Signaling by Estrogen Receptor α

作者：Hui Qi, Enpu Shen, Beibei Li, Zhiwen Wu, Yongsheng Jie, Rui Zheng, Xiong Shu, Lei Chen, DANPING Liu, Cheng’ai Wu · 发表于：Research Square · 年份：2022 · DOI：10.21203/rs.3.rs-2006386/v1 · 研究领域：Extracellular vesicles in disease、Reproductive System and Pregnancy、MicroRNA in disease regulation

Abstract Background: Exosomes derived from bone marrow stem cells (BMSC-Exos) are considered as candidates for osteoporosis (OP) therapy. Estrogen is critical in the maintenance of bone homeostasis. However, the role of estrogen and/or its receptor in BMSC-Exos treatment of OP, as well as its methods of regulation during this process remain unclear.Methods: BMSCs were cultured and characterized. Ultracentrifugation was performed to collect BMSC-Exos. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to identify BMSC-Exos. We examined the effects of BMSC-Exos on the proliferation, osteogenic differentiation, mineralization, and cell cycle distribution of MG-63 cells. The protein expression of estrogen receptor α (ERα) and the phosphorylation of extracellular signal-regulated kinase (ERK) were investigated through western blotting. We determined the effects of BMSC-Exos on the prevention of bone loss in female rats. The female SD rats were divided into three groups: the sham group, ovariectomized (OVX) group, and the OVX + BMSC-Exos group. Bilateral ovariectomy was performed in the OVX and OVX + BMSC-Exos groups, while a similar volume of adipose tissue around the ovary was removed in the sham group. The rats in OVX+BMSC-Exos group were given BMSC-Exos after 2 weeks of surgery. Micro-CT scanning and histological staining were used to evaluate the in vivo effects of BMSC-Exos.Results: BMSC-Exos significantly upregulated ...