Contextual Regulation of Skeletal Physiology by Notch Signaling

This article reviews the past 2 years of research on Notch signaling as it relates to bone physiology, with the goal of reconciling seemingly discrepant findings and identifying fruitful areas of potential future research.

Conditional animal models and high-throughput omics have contributed to a greater understanding of the context-dependent role of Notch signaling in bone. However, significant gaps remain in our understanding of how spatiotemporal context and epigenetic state dictate downstream Notch phenotypes. Biphasic activation of Notch signaling orchestrates progression of mesenchymal progenitor cells through the osteoblast lineage, but there is a limited understanding of ligand- and receptor-specific functions. Paracrine Notch signaling through non-osteoblastic cell types contributes additional layers of complexity, and we anticipate impactful future work related to the integration of these cell types and signaling mechanisms.