Osteocyte mitochondria regulate angiogenesis of transcortical vessels

Peng Liao, Long Chen, Hao Zhou, Jiong Mei, Ziming Chen, Bingqi Wang, Jerry Q. Feng, Guangyi Li, Sihan Tong, Jian Zhou, Siyuan Zhu, Yu Qian, Yao Zong, Weiguo Zou, Hao Li, Wenkan Zhang, Meng Yao, Yiyang Ma, Peng Ding, Yidan Pang, Chuan Gao, Jialun Mei, Senyao Zhang, Changqing Zhang (), Delin Liu (), Minghao Zheng () and Junjie Gao ()
Additional contact information
Peng Liao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Long Chen: Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences
Hao Zhou: The Second Affiliated Hospital of Zhejiang University School of Medicine
Jiong Mei: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Ziming Chen: Medical School, The University of Western Australia
Bingqi Wang: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jerry Q. Feng: Shanxi Medical University School and Hospital of Stomatology, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials
Guangyi Li: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Sihan Tong: 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
Siyuan Zhu: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yu Qian: The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)
Yao Zong: Medical School, The University of Western Australia
Weiguo Zou: 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
Wenkan Zhang: The Second Affiliated Hospital of Zhejiang University School of Medicine
Meng Yao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yiyang Ma: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Peng Ding: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yidan Pang: 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
Jialun Mei: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Senyao Zhang: 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
Delin Liu: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Minghao Zheng: Medical School, The University of Western Australia
Junjie Gao: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Transcortical vessels (TCVs) provide effective communication between bone marrow vascular system and external circulation. Although osteocytes are in close contact with them, it is not clear whether osteocytes regulate the homeostasis of TCVs. Here, we show that osteocytes maintain the normal network of TCVs by transferring mitochondria to the endothelial cells of TCV. Partial ablation of osteocytes causes TCV regression. Inhibition of mitochondrial transfer by conditional knockout of Rhot1 in osteocytes also leads to regression of the TCV network. By contrast, acquisition of osteocyte mitochondria by endothelial cells efficiently restores endothelial dysfunction. Administration of osteocyte mitochondria resultes in acceleration of the angiogenesis and healing of the cortical bone defect. Our results provide new insights into osteocyte-TCV interactions and inspire the potential application of mitochondrial therapy for bone-related diseases.

Date: 2024
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DOI: 10.1038/s41467-024-46095-0

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