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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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Correspondence to Lei Zhang.

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Lei Zhang, Qinghai Wang, Hang Su, and Jiaxiang Cheng declare that they have no conflict of interest.

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No human studies were carried out by the authors for this article. All animal studies were carried out in accordance with the Guide for the Care and Use of Laboratory Animals (8th edition, NIH), and were approved by the ethical committee of Cangzhou Central Hospital.

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Zhang, L., Wang, Q., Su, H. et al. Exosomes from Adipose Tissues Derived Mesenchymal Stem Cells Overexpressing MicroRNA-146a Alleviate Diabetic Osteoporosis in Rats. Cel. Mol. Bioeng. 15, 87–97 (2022). https://doi.org/10.1007/s12195-021-00699-4

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Keywords

  • Diabetic osteoporosis
  • miR-146a
  • MSCs
  • Exosomes
  • Inflammasome