The calcium-sensing receptor in bone metabolism: from bench to bedside and back

Abstract

Calcium released in the bone microenvironment during remodeling is a major factor in regulating bone cells. Osteoblast and osteoclast proliferation, differentiation, and apoptosis are influenced by local extracellular calcium concentration. Thus, the calcium-sensing properties of skeletal cells can be exploited in order to modulate bone turnover and can explain the bone anabolic effects of agents developed and employed to revert osteoporosis.

Osteoclast differentiation from human blood precursors on biomimetic calcium-phosphate substrates

“…As reported by the group of Brandi, on the active bone surfaces only modest and gradual changes of Ca2+, ranging from 0.5 mM during formation to ≥2 mM during resorption, occur, and these values are very close to the calcium oscillations detected in our study by ICP-OES in the direct contact assay [45]. Therefore, we do not expect a major effect of calcium on the behaviour of osteoclasts in our protocol.…”

“…This did not happen for osteoclasts on TCPS, which had a regular morphology, with evident and their progenitors show a cell membrane calcium receptor [45], and intracellular calcium is tightly regulated by calcium entry from the extracellular fluid, and a mechanism involving Ca ++ and calcineurin leads to osteoclast differentiation [46,47]. Also, extracellular calcium concentration has been found to signal for osteoclasts survival and differentiation by modulation of the cytosolic Ca ++ levels [48,49], but the role of calcium signaling in osteoclasts is still under intense study [50,51].…”

Amyloid β Peptide Enhances RANKL-Induced Osteoclast Activation through NF-κB, ERK, and Calcium Oscillation Signaling

“…These findings are consistent with our results on the ERK phosphorylation and NF-κB signaling pathways. Given that calcium oscillation signaling is essential for OC differentiation, gene transcription, and bone resorption [15,22], and that activated calcium signaling promotes Aβ formation and the amyloid pathology of AD [23], these intersections lead us to explore and proved eventually that Ca 2+ pathways also play a critical role in Aβ-mediated OC differentiation and activation. Together, these signaling cascades may initiate the common pathway of NFATc1, a master regulator of OC activation, expression, and translocation into the nucleus, which eventually induces OC-specific gene transcription to enhance OC function.…”

Clinical characterization of a novel calcium sensing receptor genetic alteration in a Greek patient with autosomal dominant hypocalcemia type 1

“…However, the data from in vivo studies, which are controversial, suggest that CaSR activation leads to enhanced bone resorption and mild osteopenia, although similar implications in humans have not been demonstrated as yet. 11 From the very few studies examining the BMD of patients with ADH, it seems that patients with different activating CaSR mutations may present with low, normal or high BMD. [12][13][14][15] It is interesting to note that our patient, as well as the three patients with increased BMD previously reported, 12 all harbored mutations within the same region of the extracellular domain of the receptor.…”