Calcium signaling in osteoclasts

Abstract

It has long been known that many bone diseases, including osteoporosis, involve abnormalities in osteoclastic bone resorption. As a result, there has been intense study of the mechanisms that regulate both the differentiation and bone resorbing function of osteoclast cells. Calcium (Ca2+) signaling appears to play a critical role in the differentiation and functions of osteoclasts. Cytoplasmic Ca2+ oscillations occur during RANKL-mediated osteoclastogenesis. Ca2+ oscillations provide a digital Ca2+ signal that induces osteoclasts to up-regulate and autoamplify nuclear factor of activated T cells c1 (NFATc1), a Ca2+/calcineurin-dependent master regulator of osteoclastogenesis. Here we review previous studies on Ca2+ signaling in osteoclasts as well as recent breakthroughs in understanding the basis of RANKL-induced Ca2+ oscillations, and we discuss possible molecular players in this specialized Ca2+ response that appears pivotal for normal bone function.

Nanocrystalline silicon substituted hydroxyapatite effects on osteoclast differentiation and resorptive activity

“…16,17 Many different stimuli have been shown to regulate Ca 2+ concentrations in osteoclasts and extracellular acidification has been described as causing a decrease in intracellular Ca 2+ concentration in isolated chicken osteoclasts. 57 The lower Ca 2+ content observed in the present study with osteoclast-like cells cultured on nano-HA disks in comparison to cells cultured on nano-SiHA samples ( Figure 9C) can be related to higher extracellular acidification produced by these cells on nano-HA surface than on nano-SiHA surface, as demonstrated by the geometry of the resorption cavities observed on this material ( Fig. 11A and 11B).…”

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

“…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].…”

TRAF3 negatively regulates calcineurin‐NFAT pathway by targeting calcineurin B subunit for degradation

“…*, P < 0.05. and differentiation (32). Various disorders, such as osteoporosis (33), cardiac hypertrophy (34), Down's syndrome, and Alzheimer's disease (35,36) are closely related to aberrant CN activity. Patients treated with cyclosporin A, a potent inhibitor for CN activity, have a 65-100-fold higher risk of squamous cell carcinoma (SCC) than normal population (37).…”