Relevance of Notch Signaling for Bone Metabolism and Regeneration

Notch1-4 receptors and their signaling pathways are expressed in almost all organ systems and play a pivotal role in cell fate decision by coordinating cell proliferation, differentiation and apoptosis. Differential expression and activation of Notch signaling pathways has been observed in a variety of organs and tissues under physiological and pathological conditions. Bone tissue represents a dynamic system, which is constantly remodeled throughout life. In bone, Notch receptors have been shown to control remodeling and regeneration. Numerous functions have been assigned to Notch receptors and ligands, including osteoblast differentiation and matrix mineralization, osteoclast recruitment and cell fusion and osteoblast/osteoclast progenitor cell proliferation. The expression and function of Notch1-4 in the skeleton are distinct and closely depend on the temporal expression at different differentiation stages. This review addresses the current knowledge on Notch signaling in adult bone with emphasis on metabolism, bone regeneration and degenerative skeletal disorders, as well as congenital disorders associated with mutant Notch genes. Moreover, the crosstalk between Notch signaling and other important pathways involved in bone turnover, including Wnt/beta-catenin, BMP and RANKL/OPG, are outlined.

Automated summary

Notch1-4 receptors and their signaling pathways are crucial in cell fate decision by coordinating cell proliferation, differentiation and apoptosis, with differential expression and activation observed in various organs and tissues. In bone, Notch receptors control remodeling and regeneration, with distinct expression and function depending on differentiation stages. The crosstalk between Notch signaling and other pathways in bone turnover, including Wnt/beta-catenin, BMP and RANKL/OPG, is outlined.