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, Zong Yao, 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, Junjie Gao
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.