Osteoclast-derived exosomal miR-30a-3p promotes lead exposure-induced osteoporosis by triggering osteoblastic pyroptosis
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.
Authors
- Jie Ding (ORCID: https://orcid.org/0000-0002-0016-1141)
- Hengdong Zhang (ORCID: https://orcid.org/0000-0002-6292-8459)
- Yinnong Jia (ORCID: https://orcid.org/0000-0001-5980-9275)
- Luna Wang
- Ming Xu (ORCID: https://orcid.org/0000-0001-8846-2880)
- Yuanfang Chen (ORCID: https://orcid.org/0000-0002-1109-8491)
- Tingting Yu (ORCID: https://orcid.org/0000-0003-1694-7592)
- Xu He (ORCID: https://orcid.org/0000-0002-8113-2106)
- Yan An (ORCID: https://orcid.org/0000-0003-2838-8169)
- Liu Ouyang (ORCID: https://orcid.org/0000-0002-1404-1263)
- Baoli Zhu (ORCID: https://orcid.org/0000-0001-9408-8266)
- Wen Wang (ORCID: https://orcid.org/0009-0006-0978-8393)
- Hang Zhang (ORCID: https://orcid.org/0000-0002-2493-0806)
- Yue Gao (ORCID: https://orcid.org/0000-0001-7611-212X)
Institutions
- Kunming University (CN)
- Chinese Center For Disease Control and Prevention (CN)
- Kunming Medical University (CN)
- Soochow University (CN)
- Nanjing Health and Health Commission (CN)
- People 's Hospital of Jilin Province (CN)
- Jilin City Central Hospital (CN)
- Jiangsu Provincial Center for Disease Control and Prevention (CN)
- Nanjing Municipal Center for Disease Control And Prevention (CN)
- Wuhan Union Hospital (CN)
- Huazhong University of Science and Technology Hospital (CN)
- Union Hospital (CN)
- Huazhong University of Science and Technology (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Clinical Science
- Published
- 2025-03-20
- DOI
- https://doi.org/10.1042/cs20243438
- Citations
- 6
- Primary Topic
- Trace Elements in Health
- Type
- article
- Field-Weighted Citation Impact
- 6.72
Funders
- Natural Science Foundation of Jiangsu Province