Functional involvement of calcium in the homologous up‐regulation of the 1,25‐dihydroxyvitamin D₃ receptor in osteoblast‐like cells

Abstract

In several cell types 1,25_dihydroxyvitamin Da (1,25(OH)*D,) causes up-regulation of its receptor. The present study demonstrates that in the osteoblast-like cell line UMR 106 this up-regulation is inhibited by two different calcium channel blockers (nitrendipine, verapamil). Also with chelating extracellular calcium (EGTA) and by inhibition of calcium release from intracellular stores (TMB-8) comparable results were obtained. These findings indicate that calcium is functionally involved in this cellular response to the steroid hormone 1,25(OHXD,. Moreover, data obtained with EGTA show that the l,ZS(OHXD, receptor level is closely regulated by the extracellular calcium concentration.1,25-Dihydroxyvitamin D3; Calcium; 1,25(0H)zDs receptor up-regulation

Alendronate Interacts With the Inhibitory Effect of 1,25(OH)2D3 on Parathyroid Hormone-Related Protein Expression In Human Osteoblastic Cells

“…This was a somewhat unexpected finding because Ca 2ϩ channel blockers have been shown to inhibit VDR upregulation by 1,25(OH) 2 D 3 in rat osteoblast-like UMR 106 cells. (53) In this regard, differences in VDR regulatory mechanisms appear to occur among different species and diverse osteoblastic cell types. (33,34) In any event, these data suggest that a nongenomic effect of 1,25(OH) 2 D 3 involving Ca 2ϩ entry into hOB cells does not appear to significantly interact with its PTHrP-inhibiting effect.…”

Characterization of a 1,25(OH)2‐vitamin D3‐responsive capacitative Ca2+ entry pathway in rat osteoblast‐like cells

“…As in most non‐excitable cells [Putney and Bird, 1993; Clapham, 1995], receptor‐activated Ca 2+ signaling in osteoblasts involves two phases: transient Ca 2+ release from inner IP 3 ‐sensitive stores and a more prolonged phase of Ca 2+ entry from the outside through Ca 2+ channels in the plasma membrane [Said Ahmed et al, 2000]. It has been proposed that in bone cells of the osteoblast lineage, the influx of Ca 2+ from the outside may act in concert with, and in response to, microenvironmental stimuli (i.e., mechanical forces, hormonal signals) to regulate not only cell metabolism and function within the short term, but also transcriptional rates of diverse genes involved in both osteoblast function and differentiation, and paracrine signaling between bone‐forming osteoblasts and bone‐resorbing osteoclasts at local sites of bone remodeling [Van Leeuwen et al, 1990; Duncan et al, 1998]. Voltage‐dependent Ca 2+ channels (VDCCs) particularly those from the L‐type, are well described in osteoblastic cells and account for most of the sustained Ca 2+ influx phase frequently observed in the Ca 2+ response of these cells to many hormonal stimuli linked to activation of the PLCβ/IP 3 pathway [Duncan et al, 1998; Farach‐Carson and Ridall, 1998].…”

Vitamin D analogues: from molecule to clinical application

“…Studies to isolate and characterize a possible vitamin D membrane receptor are in progress. Nevertheless the functional involvement of calcium and protein kinase C in various biological responses to 1,25-(OH)*D3 has already been demonstrated in HL-60 cells and bone (Simpson et al, 1989;Van Leeuwen et al, 1990; and support the importance of both genomic and non-genomic mechanisms. Therefore, the difference in the ability of the various analogues to activate both genomic and non-genomic mechanisms may contribute to their selective actions.…”