The role of Ca²⁺/Calcineurin/NFAT signalling pathway in osteoblastogenesis

Abstract

The bone remodelling process is closely related to bone health. Osteoblasts and osteoclasts participate in the bone remodelling process under the regulation of various factors inside and outside. Excessive activation of osteoclasts or lack of function of osteoblasts will cause occurrence and development of multiple bone‐related diseases. Ca2+/Calcineurin/NFAT signalling pathway regulates the growth and development of many types of cells, such as cardiomyocyte differentiation, angiogenesis, chondrogenesis, myogenesis, bone development and regeneration, etc. Some evidences indicate that this signalling pathway plays an extremely important role in bone formation and bone pathophysiologic changes. This review discusses the role of Ca2+/Calcineurin/NFAT signalling pathway in the process of osteogenic differentiation, as well as the influence of regulating each component in this signalling pathway on the differentiation and function of osteoblasts, whereby the relationship between Ca2+/Calcineurin/NFAT signalling pathway and osteoblastogenesis could be deeper understood.

Response of mesenchymal stem cells to surface topography of scaffolds and the underlying mechanisms

“…CaM also dephosphorylates NFAT, which in turn enters the nucleus and upgrades the transcription of osteogenic-related genes. 149 Overall, when cells adhere to a rough topography surface, they have a more extended cellular morphology and a responsive intracellular tension that mediates cytoskeletal remodeling. The contractile forces on the cytoskeleton alter the expression of intracellular genes by changing the nuclear morphology and activating YAP/TAZ and calcium channels.…”

“…CaM also dephosphorylates NFAT, which in turn enters the nucleus and upgrades the transcription of osteogenic-related genes. 149…”

Receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds

“…It has been shown that normal body metabolism can produce reactive oxygen species (ROS), either endogenously by nicotinamide adenine dinucleotide phosphate oxidase (NOX) or as a by-product of the mitochondrial electron transport chain ( Ren et al, 2021 ; Zhu et al, 2022 ). ROS contains superoxide anion radicals (O 2 −), hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (-OH) and nitric oxide (NO) ( Madreiter-Sokolowski et al, 2020 ).…”

Current applications of adipose-derived mesenchymal stem cells in bone repair and regeneration: A review of cell experiments, animal models, and clinical trials

“…Bones respond to mechanical stimuli and activate corresponding signaling pathways including calcium ions, integrins, prostaglandins (PG), and nitric oxide (NO) ( Huang and Ogawa, 2010 ) ( Figure 1C ). The level of inositol 1,4,5-triphosphate (IP3) promotes the release of calcium ions and increases its cytoplasmic concentration, then activates Wnt pathway and triggers BMP-2 ( Ren et al, 2021 ). Focal adhesion kinase (FAK) is an intracellular component of the integrin signaling pathway, which eliminates osteogenic response when inactivated.…”