Exosomes from adipose derived mesenchymal stem cells alleviate diabetic osteoporosis in rats through suppressing NLRP3 inflammasome activation in osteoclasts

J Biosci Bioeng. 2021 Apr 10;S1389-1723(21)00052-9. doi: 10.1016/j.jbiosc.2021.02.007. Online ahead of print.

Abstract

Inflammation is one of major contributors of diabetic osteoporosis. Adipose derived mesenchymal stem cells (AD-MSCs) show great potential to inhibit inflammation. We investigated the anti-osteoporosis role of AD-MSCs-derived exosomes in diabetic osteoporosis and the underlying molecular mechanism. Cellular and animal diabetic osteoporosis models were created through high glucose exposure and streptozotocin injection. AD-MSCs-derived exosomes were isolated and characterized. Pro-inflammatory cytokines and osteoclast markers were determined by ELISA. Bone mineral content and density were detected to evaluate bone loss. qRT-PCR and Western blots were performed to detect the expression of target genes. AD-MSCs-derived exosomes inhibited the secretion of IL-1β and IL-18 in HG treated osteoclasts and restored the bone loss in streptozotocin-induced diabetic osteoporosis rats. Mechanistically, AD-MSCs-derived exosomes suppress NLRP3 inflammasome activation in osteoclasts, and then reduce bone resorption and recover bone loss. AD-MSCs-derived exosomes alleviate diabetic osteoporosis through suppressing NLRP3 inflammasome activation in osteoclasts, which might be a potential cell-free therapeutic approach for diabetes-induced bone loss treatment.

Keywords: Bone loss; Diabetic osteoporosis; Exosomes; NLRP3 inflammasome; Osteoclasts.