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

作者：Yue Gao, Hang Zhang, Yinnong Jia, Yuanfang Chen, Luna Wang, Jie Ding, Wen Wang, Baoli Zhu, Liu Ouyang, Xu He, Yan An, Tingting Yu, Hengdong Zhang, Ming Xu · 发表于：Clinical Science · 年份：2025 · DOI：10.1042/cs20243438 · 被引用次数：9 · 研究领域：Trace Elements in Health、Biomarkers in Disease Mechanisms、Heavy Metal Exposure and Toxicity

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 and Pb exposure. Osteoclasts (OCs) secrete microRNA-enriched exosomes, through which miR-30a-3p is transferred to osteoblasts (OBs) to induce pyroptosis, leading to the aggravation of bone loss. Mechanistically, OC-Exo-packaged miR-30a-3p triggered pyroptosis in OBs by stimulating the NLRP3 inflammasome, activating the caspase-1 pathway, and up-regulating 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 OCs and mediates OB pyroptosis, inhibiting bone formation through cellular communication in Pb-induced osteoporosis. Therefore, OC-Exo-packaged miR-30a-3p may be a novel risk factor for Pb-induced osteoporosis and holds prognostic value in evaluating bone formation.