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Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression. © 2024. The Author(s).

Citation

Peng Ding, Chuan Gao, Jian Zhou, Jialun Mei, Gan Li, Delin Liu, Hao Li, Peng Liao, Meng Yao, Bingqi Wang, Yafei Lu, Xiaoyuan Peng, Chenyi Jiang, Jimin Yin, Yigang Huang, Minghao Zheng, Youshui Gao, Changqing Zhang, Junjie Gao. Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption. Nature communications. 2024 Jun 14;15(1):5094

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PMID: 38877020

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