Since blood flow is something we can manipulate, blood flow altering bone growth is something very promising.
“Osteogenesis is categorized into two groups based on developmental histology, intramembranous and endochondral ossification. The role of blood vessels during endochondral ossification is well known, while their role in intramembranous ossification, especially the intertissue pathway, is poorly understood. Here, we demonstrate endothelial Yap/Taz is a novel regulator of intramembranous ossification in zebrafish. Appropriate blood flow is required for Yap/Taz transcriptional activation in endothelial cells and intramembranous ossification. Additionally, Yap/Taz transcriptional activity in endothelial cells specifically promotes intramembranous ossification. BMP expression by Yap/Taz transactivation in endothelial cells is also identified as a bridging factor between blood vessels and intramembranous ossification. Furthermore, the expression of Runx2 in pre-osteoblast cells is a downstream target of Yap/Taz transcriptional activity in endothelial cells. Our results provide novel insight into the relationship between blood flow and ossification by demonstrating intertissue regulation.”
“During endochondral ossification in mammalian systems, the invasion of blood vessels into the cartilage is a well-known process for converting cartilage to bone. Blood vessels in the cartilage provide osteoclast cells, which differentiate from macrophages. Vascular endothelial growth factor (VEGF) secreted by chondrocytes also promotes the replacement of cartilage”
“Yap/Taz localization and transactivation are regulated by substrate stiffness and fluid shear stress, Yap/Taz is also regarded as a mechanosensor.”
“Embryos overexpressing Yap and Taz in endothelial cells showed larger opercle volumes in very early ossification compared to controls”
“Circulation activates Yap/Taz transcriptional activity in endothelial cells and transactivated Yap/Taz promotes Bmp4 expression in endothelial cells, and Runx2 expression in precursor cells of the opercle for its ossification.”
