Exosomes from Adipose Tissues Derived Mesenchymal Stem Cells Overexpressing MicroRNA-146a Alleviate Diabetic Osteoporosis in Rats

Inflammation is one of major contributors of diabetic osteoporosis. Here, we combined adipose tissues derived mesenchymal stem cells (AD-MSCs)-derived exosomes and microRNA-146a (miR-146a) to develop more effective anti-inflammation strategy in osteoclasts. miR-146a was overexpressed in AD-MSCs and miR-146a exosomes (miR-146a-Exo) were isolated and characterized. Cellular and animal diabetic osteoporosis models were created to evaluate the anti-inflammation effect of miR-146a-Exo by using ELISA, qRT-PCR, MTT, bone resorption assay, Western blot, and bone mineral content and density analysis in vitro and in vivo. miR-146a-Exo administration presented the most potent effect on inhibition of pro-inflammatory cytokines production in high glucose-treated osteoclasts, restraint bone resorption, and restoration of the bone loss in streptozotocin-induced diabetic osteoporosis rats. Mechanistically, miR-146a-Exo suppressed the expression of TNF-α, IL-18, and IL-1β, induced the inactivation of inflammasome, and finally reduced bone resorption and recovered bone loss. Combination of AD-MSCs-Exo and miR-146a more effectively exert the anti-inflammation effect in osteoclasts, providing a potential drug for the treatment of diabetic osteoporosis.