ESPE Yearbook of Paediatric Endocrinology

In brief: This basic research article provides new insights into osteocyte-transcortical vessel interactions and potentially opens up new therapeutic perspectives for bone diseases associated with vascular damage.

Commentary: The bone vascular system has been shown to play a critical role in controlling bone development and wound healing and provides a microenvironment for the differentiation and maturation of haematopoietic and immune cells in bone marrow. In particular, capillaries that originate in the bone marrow and cross the cortical bone, named transcortical vessels (TCVs), appear to play an essential role in communication between the bone marrow vascular system and the external circulation. Although TCVs occupy over 86% of the cortical bone canals, the regulatory factors that determine the formation and maintenance of TCVs are still unknown. Osteocytes, the major cell component of cortical bone, are in close contact with endothelial cells of TCVs. Therefore, it has been hypothesised that osteocytes may act as a critical mediator in the regulation of the TCV homeostasis.

This study shows that osteocytes maintain a normal TCV network by transferring mitochondria to endothelial cells in cortical bone. Partial ablation of osteocytes causes TCV regression and reduction of angiogenic genes. Inhibition of mitochondrial transfer by conditional knockout of Rhot1 in osteocytes also leads to regression of the TCV network. In contrast, MIRO1-mediated mitochondrial transfer from osteocytes to endothelial cells rescued endothelial dysfunction. Metabolomic analysis further revealed that mitochondrial transfer induces the biosynthesis and SPHK1-dependent catalysis of D-sphingosine. Administration of D-sphingosine promotes TCVs and bone formation in mouse cortical bone defect model.

These findings reveal a unique mechanism involved in the vascular homeostasis of cortical bone and open new therapeutic perspectives for bone diseases associated with vascular damage.