Exploring the impact of gut microbiota-mediated regulation of exosomal miRNAs from bone marrow mesenchymal stem cells on the regulation of bone metabolism.

Background: Osteoporosis, which is a prevalent metabolic bone disease, is closely associated with imbalances in the gut microbiota.

Methods: 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.

Results: 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.

Conclusions: 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.