Mitochondria from osteolineage cells regulate myeloid cell-mediated bone resorption

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 () and Junjie Gao ()
Additional contact information
Peng Ding: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Chuan Gao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jian Zhou: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jialun Mei: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Gan Li: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Delin Liu: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Hao Li: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Peng Liao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Meng Yao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Bingqi Wang: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yafei Lu: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Xiaoyuan Peng: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Chenyi Jiang: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jimin Yin: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yigang Huang: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Minghao Zheng: University of Western Australia
Youshui Gao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Changqing Zhang: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Junjie Gao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-49159-3

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