Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption.

1. Nat Commun. 2024 Jun 14;15(1):5094. doi: 10.1038/s41467-024-49159-3. Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption. Ding P(#)(1)(2), Gao C(#)(1)(2), Zhou J(#)(1)(2), Mei J(#)(1)(2), Li G(1)(2), Liu D(1)(2), Li H(1)(2), Liao P(1)(2), Yao M(1)(2), Wang B(1)(2), Lu Y(1)(2), Peng X(1), Jiang C(1), Yin J(1), Huang Y(1), Zheng M(3), Gao Y(4), Zhang C(5)(6), Gao J(7)(8). Author information: (1)Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. (2)Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. (3)Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, WA, 6009, Australia. (4)Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. gaoyoushui@sjtu.edu.cn. (5)Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. zhangcq@sjtu.edu.cn. (6)Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. zhangcq@sjtu.edu.cn. (7)Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. colingjj@163.com. (8)Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200233, Shanghai, China. colingjj@163.com. (#)Contributed equally 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). DOI: 10.1038/s41467-024-49159-3 PMCID: PMC11178781 PMID: 38877020 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no competing interests.