Local coordination between intracortical bone remodeling and vascular development in human juvenile bone

Christina Møller Andreasen*, Bilal Mohamad El-Masri, Birgit MacDonald, Kaja Søndergaard Laursen, Malene Hykkelbjerg Nielsen, Jesper Skovhus Thomsen, Jean Marie Delaisse, Thomas Levin Andersen


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Although failure to establish a vascular network has been associated with many skeletal disorders, little is known about what drives development of vasculature in the intracortical bone compartments. Here, we show that intracortical bone resorption events are coordinated with development of the vasculature. We investigated the prevalence of vascular structures at different remodeling stages as well as their 3D organization using proximal femoral cortical bone from 5 girls and 6 boys (aged 6–15 years). A 2D analysis revealed that non-quiescent intracortical pores contained more vascular structures than quiescent pores (p < 0.0001). Type 2 pores, i.e., remodeling of existing pores, had a higher density of vascular structures than type 1 pores, i.e., de novo created pores (p < 0.05). Furthermore, pores at the eroded-formative remodeling stage, had more vascular structures than pores at any other remodeling stage (p < 0.05). A 3D reconstruction of an intracortical remodeling event showed that osteoclasts in the advancing tip of the cutting cone as well as preosteoclasts in the lumen expressed vascular endothelial growth factor-A (VEGFA), while VEGFA-receptors 1 and 2 mainly were expressed in endothelial cells in the adjacent vasculature. Consequently, we propose that the progression of the vascular network in intracortical remodeling events is driven by osteoclasts expressing VEGFA. Moreover, the vasculature is continuously reconfigured according to the demands of the remodeling events at the surrounding bone surfaces.

Antal sider10
StatusUdgivet - aug. 2023

Bibliografisk note

Funding Information:
We thank Søren Harving from the Department of Orthopedic Surgery, Aalborg University Hospital for the collection of bone samples. We thank The VELUX Foundations for funding support ( VELUX34368 ) and donation of the μCT scanner ( VELUX26922 ), The Aase and Ejnar Danielsen Foundation ( 10-001584 ) and The Danish Southern Region Research Grant ( 15/24851 ).

Publisher Copyright:
© 2023 The Author(s)


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