Relevance of Notch Signaling for Bone Metabolism and Regeneration

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.

Turning gray selenium into a nanoaccelerator of tissue regeneration by PEG modification

“…Tissue regeneration is a complex process involving multiple cell types and various signaling pathways. The signaling pathways involved in tissue regeneration mainly include WNT [ 59 ], FGF [ 60 ], IGF [ 61 ], BMP [ 62 ], Notch [ 63 ], Hippo [ 64 ], Hedgehog [ 65 ], and VEGF [ 66 ]. The cell types involved in regeneration depend on the type of regenerating tissue.…”

Probing Notch1-Dll4 signaling in regulating osteogenic differentiation of human mesenchymal stem cells using single cell nanobiosensor

“…It has been shown that hMSCs have the potential to differentiate into different lineages, including osteoblasts (bone), neuroblasts (neural tissue), adipoblasts (fat), myoblasts (muscle), and chondroblasts (cartilage) 3 , 4 . In particular, osteogenic induction of hMSCs differentiation in conjunction with tissue engineering approaches has been exploited to provide an alternative method besides autologous bone graft to replace or restore damaged bone tissues 5 . This evidence demonstrates the application of hMSCs as a promising cell source in bone tissue engineering, given their regenerative properties.…”

Probing Notch1-Dll4 Signaling in Regulating Osteogenic Differentiation of Human Mesenchymal Stem Cells using Single Cell Nanobiosensor

“…Notch signaling is an evolutionarily conserved, intercellular, and contact-dependent signaling pathway which regulates cell fate decisions and plays a significant role during development and organogenesis [5][6][7][8][9][10]. Many studies have demonstrated the critical role of Notch signaling in cell fate determination, cell proliferation, differentiation, and apoptosis in various cell types [11][12][13][14].…”