2. Academic Validation
  3. Osteocyte mitochondria regulate angiogenesis of transcortical vessels

Osteocyte mitochondria regulate angiogenesis of transcortical vessels

  • Nat Commun. 2024 Mar 21;15(1):2529. doi: 10.1038/s41467-024-46095-0.
Peng Liao # 1 2,  Long Chen # 3,  Hao Zhou # 4,  Jiong Mei 1,  Ziming Chen 5 6,  Bingqi Wang 1 2,  Jerry Q Feng 7,  Guangyi Li 1,  Sihan Tong 1 2,  Jian Zhou 1 2,  Siyuan Zhu 8,  Yu Qian 9,  Yao Zong 5 6,  Weiguo Zou 1 2 3,  Hao Li 1 2,  Wenkan Zhang 4,  Meng Yao 1 2,  Yiyang Ma 1 2,  Peng Ding 1 2,  Yidan Pang 1 2,  Chuan Gao 1 2,  Jialun Mei 1 2,  Senyao Zhang 1 2,  Changqing Zhang 10 11,  Delin Liu 12 13,  Minghao Zheng 14 15,  Junjie Gao 16 17
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 State Key Laboratory of Cell Biology, 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, Shanghai, China.
  • 4 Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 5 Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, Western Australia, Australia.
  • 6 Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia.
  • 7 Shanxi Medical University School and Hospital of Stomatology, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, China.
  • 8 Department of General Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 9 Department of Orthopedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
  • 10 Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhangcq@sjtu.edu.cn.
  • 11 Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhangcq@sjtu.edu.cn.
  • 12 Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. liudelin_doc@126.com.
  • 13 Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. liudelin_doc@126.com.
  • 14 Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, Western Australia, Australia. minghao.zheng@uwa.edu.au.
  • 15 Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia. minghao.zheng@uwa.edu.au.
  • 16 Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. colingjj@163.com.
  • 17 Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. colingjj@163.com.
  • # Contributed equally.
PMID: 38514612 DOI: 10.1038/s41467-024-46095-0
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.

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