After binding to its receptor RANK on osteoclasts and osteoclast precursors, RANKL stimulates osteoclast formation, activation and survival, thus leading to increased bone resorption [ 18].
Calcitonin is a 32-amino acid peptide hormone produced by the parafollicular cells in the thyroid gland that possess potent anti-resorptive effects by binding to its receptor on osteoclasts [ 7].
RANKL is a cytokine produced by osteoblasts that stimulates osteoclast activity and inhibits osteoclast apoptosis through binding to its receptor, RANK, which is expressed on osteoclasts and their precursors [ 3].
RANKL mediates its function by binding to its cell-surface receptor RANK on osteoclast precursor cells and osteoclasts, thus stimulating differentiation and activation of osteoclasts.
RANKL binding to its receptor RANK expressed on osteoclast precursors is able to activate NF-kB signaling, leading to the transcription of key osteoclastogenic factors [ 8].
By binding to its receptor RANK on osteoclastic precursors, RANKL controls the differentiation, proliferation, and survival of osteoclasts.
The currently held view is that PTH stimulates osteoclast formation by binding to its receptor, PTH receptor 1 (PTHR1), on stromal/osteoblastic cells and thereby increases production of receptor activator of NFkB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) and suppresses the RANKL decoy receptor osteoprotegerin (OPG) [33] [36].
RANKL activates the development of pre-osteoclasts to become mature osteoclasts, while osteoprotegerin or OPG serves as a secreted receptor of RANKL (decoy receptor), resulting in inhibition of RANKL binding to its cell surface receptor and activation of osteoclast maturation.
RANKL mediates the process of osteoclastogenesis by binding to its RANK, which is expressed on mononuclear osteoclast precursors.
PU.1 in turn positively regulates the expression of the receptor of macrophage-colony stimulating factor (M-CSF), named c-fms, as well as of the receptor activator of nuclear factor Kappa B (RANK) that, upon binding to its ligand RANKL, triggers the fusion and differentiation of osteoclast precursors into mature osteoclasts [ 18].
