Research Progress on the Mechanism of Promoting Osteogenesis through Vascular Osteogenic Coupling based on Notch/Hes1/DLL4 Signaling Pathway
PENG Randong, LIU Hongxi, YANG Wenbo, ZHOU Jun, WANG Yulei, YANG Yang, YIN Xuesong, BI Junwei*
Vascular osteogenic coupling is a core process in bone repair and regeneration, providing critical support for the steady-state reconstruction of bone tissue by coordinating the dynamic balance between angiogenesis and bone formation. The Notch signaling pathway, along with its key effector molecule Hes1 and ligand DLL4, plays a crucial regulatory role in this process. As an important ligand of the Notch pathway, DLL4 can promote osteogenic differentiation by enhancing H-type vessel formation under mechanical stimuli (such as stretching) or chemical induction. H-type vessels, as a specific vascular subtype, directly couple angiogenesis and bone formation through the secretion of factors such as VEGF and BMP2 in bone defect models, activation of the Notch/Hes1/DLL4 pathway can significantly enhance the expression of osteogenic markers and angiogenic fac tors, thereby improving bone microstructure and mechanical properties. The Notch signal is cross regulated with pathways such as PI3K/AKT and BMP, indicating the existence of a multi pathway synergistic mechanism. Future research needs to analyze the molecular details of Notch/Hes1/DLL4 in spatiotemporal specific regulation, and ex plore precise intervention strategies targeting this pathway, providing new ideas for bone metabolism diseases and bone defect repair.
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