Relevance of Notch Signaling for Bone Metabolism and Regeneration
Open Access
- 29 January 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (3), 1325
- https://doi.org/10.3390/ijms22031325
Abstract
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/β-catenin, BMP and RANKL/OPG, are outlined.Funding Information
- Else Kröner-Fresenius-Stiftung (2017_A22)
- Deutsche Forschungsgemeinschaft (KE 2179/2-1, 97850925 - SFB 854)
- European Structural and Investment Funds (ZS/2016/08/80645)
This publication has 121 references indexed in Scilit:
- Notch receptor–ligand binding and activation: Insights from molecular studiesSeminars in Cell & Developmental Biology, 2012
- Notch signaling and Notch signaling modifiersThe International Journal of Biochemistry & Cell Biology, 2011
- Alagille syndrome: pathogenesis, diagnosis and managementEuropean Journal of Human Genetics, 2011
- Notch: Architect, Landscaper, and Guardian of the IntestineGastroenterology, 2011
- Notch signaling components are upregulated during both endochondral and intramembranous bone regenerationJournal of Orthopaedic Research, 2011
- HES1 (Hairy and Enhancer of Split 1) Is a Determinant of Bone MassPublished by Elsevier BV ,2011
- YB-1 Acts as a Ligand for Notch-3 Receptors and Modulates Receptor ActivationPublished by Elsevier BV ,2009
- Role of hypoxia-inducible factor-1α in angiogenic–osteogenic couplingJournal of Molecular Medicine, 2009
- Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancerProceedings of the National Academy of Sciences of the United States of America, 2009
- Dimorphic effects of Notch signaling in bone homeostasisNature Medicine, 2008