Osteoclast-derived exosomal miR-30a-3p promotes lead exposure-induced osteoporosis by triggering osteoblastic pyroptosis.

Abstract

High lead (Pb) burden in humans disrupts bone homeostasis and can induce osteoporosis. Here, we report that osteoclast-derived exosomes (OC-Exos) were enriched in the plasma of patients with low bone mineral density (BMD) and Pb-exposure. Osteoclasts secrete microRNA-enriched exosomes, through which miR-30a-3p is transferred to osteoblasts to induce pyroptosis, leading to the aggravation of bone loss. Mechanistically, OC-Exo-packaged miR-30a-3p triggered pyroptosis in osteoblasts by stimulating the NLRP3 inflammasome, activating the caspase-1 pathway, and upregulating the expression of IL-1 and IL-18. Depletion of miR-30a-3p abolished the effects of OC-Exo and alleviated the symptoms of Pb-induced osteoporosis. Collectively, our results suggest that miR-30a-3p is highly expressed in exosomes derived from osteoclasts and mediates osteoblast pyroptosis, inhibiting bone formation through cellular communication in Pb-induced osteoporosis. Therefore, OC-Exo-packaged miR-30a-3p may be a novel risk factor of Pb-induced osteoporosis and holds prognostic value in evaluating bone formation.