Abstract
Bone homeostasis is a function of the constant balancing acts between osteoclasts and osteoblasts, regulated by numerous factors in cellular and molecular levels. Calcineurin-NFAT pathway plays critical roles in bone homeostasis by regulating many aspects of bone development and remodeling. NFATc1 is the master transcription factor of osteoclasts, acting downstream of RANKL (receptor activator of nuclear factor-κB ligand) to control osteoclastogenesis. NFATc1 also plays important role in osteoblastogenesis, its increased nuclear occupancy in osteoblasts causes osteopetrosis by regulating chemokine and Wnt pathways. Targeting NFAT pathway may provide therapeutic avenues for treating bony disorders.
Highlights
Bone homeostasis is a function of the constant balancing acts between osteoclasts and osteoblasts, regulated by numerous factors in cellular and molecular levels
Activation of the surface receptors leads to the activation of Phosphoinositide Phospholipase C (PLC) that catalyzes the generation of inositol-1,4,5-trisphosphate (IP3) which interacts with its receptor (IP3R) on the surface of the endoplasmic reticulum (ER), inducing efflux of calcium from the ER and the subsequent depletion of the store calcium
RANKL-RANK signaling stimulates NFATc1 to induce the expression of a number of genes within osteoclasts to activate differentiation of osteoclast leading to bone resorption and remodeling
Summary
Osteoclasts are the multinucleated giant cells that decalcify the bone matrix and degrade collagens by performing acid decalcification and proteolytic degradation, while osteoblasts produce bone matrix protein and maintain mineralization to counterbalance the action of osteoclasts [1,2]. Bone homeostasis is such a micro-sculpting process regulated by the intricate interplay between these two opposing cell types that are derived from the different lineage: osteoclasts from myeloid precursors of hematopoietic stem cell, and osteoblasts from the multipotent mesenchymal progenitors of bone marrow [1,2] (Figure 1).
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