Notch signalling in alveolar bone development and regeneration: A critical regulator for osteoblasts to osteocytes transitioning

Cell fate determination is controlled by a complex network of cell signalling pathways. The process of osteoblasts transforming into osteocytes can be described as several distinct stages: from osteoblasts to early osteocytes, then to mature osteocytes, deeply embedded in the bone matrix within spaces called lacunae and canaliculi. During this transition, the committed osteoblast undergoes significant changes, including loss of proliferative capacity, the extension of multiple slender processes, and the secretion of minerals onto the collagenous scaffold. These osteocytes are arranged in an ordered manner with respect to neighbouring cells, suggesting that osteoblast-to-osteocyte transition is a tightly regulated developmental event. In this review, we summarise recent findings on Notch expression during osteoblast-to-osteocyte transition and propose a regulatory role for Notch in coordinating adjacent osteoblast activity during this process. We further discuss the implications of Notch signalling in the alveolar bone, as emerging data indicate that Notch participates in the osteogenic commitment of periodontal and alveolar progenitor cells, modulates force-driven remodelling, contributes to inflammatory osteolysis in periodontitis, and presents opportunities for biomaterial-guided alveolar bone regeneration and improved osseointegration around dental implants. This review highlights Notch as a potential master regulator of alveolar bone biology, suggesting that precise spatial and temporal control of Notch signalling may offer new therapeutic avenues to maintain alveolar bone homeostasis.