Notch expressed by osteocytes plays a critical role in mineralisation.

ABSTRACT

Notch is actively involved in various life processes including osteogenesis; however, the role of Notch signalling in the terminal mineralisation of bone is largely unknown. In this study, it was noted that Hey1, a downstream target of Notch signalling was highly expressed in mature osteocytes compared to osteoblasts, indicating a potential role of Notch in osteocytes. Using a recently developed thermosensitive cell line (IDG-SW3), we demonstrated that dentin matrix acidic phosphoprotein 1 (DMP1) expression was inhibited and mineralisation process was significantly altered when Notch pathway was inactivated via administration of N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch. Dysregulation of Notch in osteocyte differentiation can result in spontaneous deposition of calcium phosphate on collagen fibrils, disturbed transportation of intracellular mineral vesicles, alteration of mineral crystal structure, decreased bonding force between minerals and organic matrix, and suppression of dendrite development coupled with decreased expression of E11. In conclusion, the evidence presented here suggests that Notch plays a critical role in osteocyte differentiation and biomineralisation process. KEY MESSAGES Notch plays a regulatory role in osteocyte phenotype. Notch modulates the mineralisation mediated by osteocytes. Notch activity influences the ultrastructural properties of bone mineralisation.