He Bin, Shen Xianglin, Li Feng, Zhou Rudan, Xue Haiyan, Fan Xianqiu, Wang Zhihua, Guo Xinpeng, Fan Yu, Luo Guanghu, Zhang Xiujun, Zheng Hongyu
School of Public Health, North China University of Science and Technology, 21 Bohai Road, Cao Fei Dian, Tangshan, 063210, Hebei, China.
International Science & Technology Cooperation Base of Geriatric Medicine, Tangshan, 063210, Hebei, China.
Stem Cell Res Ther. 2025 Mar 18;16(1):143. doi: 10.1186/s13287-025-04256-y.
Osteoporosis, which is a prevalent metabolic bone disease, is closely associated with imbalances in the gut microbiota.
The ovaries of female 6-month-old Sprague-Dawley rats were surgically removed to induce osteoporosis. Subsequently, 16S rRNA sequencing was employed to characterize the gut microbiota in the osteoporotic rats. Bone marrow mesenchymal stem cells (BMSCs) were isolated from osteoporotic rats and cultured separately, and their osteogenic and adipogenic differentiation was observed. Furthermore, exosomes were extracted from these cells, and miRNA sequencing was performed on the exosomes to identify key miRNAs. Osteoporotic rats were then treated with a member of the gut microbiota, and changes in the osteogenic and adipogenic differentiation of BMSCs were observed.
In our investigation, we observed altered proportions of Firmicutes and Bacteroidetes in the guts of ovariectomized rats, which contributed to dysbiosis and subsequent changes in intestinal permeability. The BMSCs exhibited disrupted osteogenic/adipogenic differentiation, which was associated with structural damage to bones. Through the isolation of exosomes from BMSCs and subsequent miRNA analysis, we identified miR-151-3p and miR-23b-3p as potential pivotal regulators of bone metabolism. Furthermore, through 16S rRNA sequencing, we identified g_Ruminococcus and its marked capacity to ameliorate the imbalance in BMSC osteogenic/adipogenic differentiation. Intervention with g_Ruminococcus demonstrated promising outcomes, mitigating bone loss and structural damage to the tibia and femur in ovariectomized rats.
These findings highlight the significant role of g_Ruminococcus in alleviating osteoporosis induced by estrogen deficiency, suggesting its therapeutic potential for addressing postmenopausal osteoporosis through the targeted modulation of BMSC-derived exosomal miR-151-3p and miR-23b-3p.
骨质疏松症是一种常见的代谢性骨病，与肠道微生物群失衡密切相关。
手术切除6月龄雌性Sprague-Dawley大鼠的卵巢以诱导骨质疏松症。随后，采用16S rRNA测序对骨质疏松大鼠的肠道微生物群进行表征。从骨质疏松大鼠中分离并分别培养骨髓间充质干细胞（BMSCs），观察其成骨和成脂分化情况。此外，从这些细胞中提取外泌体，并对外泌体进行miRNA测序以鉴定关键miRNA。然后用一种肠道微生物群成员对骨质疏松大鼠进行治疗，观察BMSCs成骨和成脂分化的变化。
在我们的研究中，我们观察到去卵巢大鼠肠道中厚壁菌门和拟杆菌门的比例发生了改变，这导致了生态失调以及随后肠道通透性的变化。BMSCs表现出成骨/成脂分化紊乱，这与骨骼的结构损伤有关。通过从BMSCs中分离外泌体并进行后续的miRNA分析，我们鉴定出miR-151-3p和miR-23b-3p是骨代谢的潜在关键调节因子。此外，通过16S rRNA测序，我们鉴定出g_瘤胃球菌及其显著改善BMSCs成骨/成脂分化失衡的能力。用g_瘤胃球菌进行干预显示出有希望的结果，减轻了去卵巢大鼠胫骨和股骨的骨质流失和结构损伤。
这些发现突出了g_瘤胃球菌在减轻雌激素缺乏诱导的骨质疏松症中的重要作用，表明其通过靶向调节BMSC来源的外泌体miR-151-3p和miR-23b-3p来治疗绝经后骨质疏松症的潜力。
