The Role of Calcium in Inflammation-Associated Bone Resorption

The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.

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Expression of extracellular calcium-sensing receptor in human osteoblastic MG-63 cell line

AJP Cell Physiology ◽

10.1152/ajpcell.2001.280.2.c382 ◽

2001 ◽

Vol 280 (2) ◽

pp. C382-C393 ◽

Cited By ~ 63

Author(s):

Toru Yamaguchi ◽

Naibedya Chattopadhyay ◽

Olga Kifor ◽

Chianping Ye ◽

Peter M. Vassilev ◽

...

Keyword(s):

Cell Line ◽

Cell Lines ◽

Northern Blot Analysis ◽

Pcr Primers ◽

Extracellular Calcium ◽

Calcium Sensing Receptor ◽

Patch Clamp Technique ◽

Calcium Sensing ◽

Specific Affinity

We have previously shown the expression of the extracellular calcium (Cao 2+)-sensing receptor (CaR) in osteoblast-like cell lines, and others have documented its expression in sections of murine, bovine, and rat bone. The existence of the CaR in osteoblasts remains controversial, however, since some studies have failed to document its expression in the same osteoblast-like cell lines. The goals of the present study were twofold. 1) We sought to determine whether the CaR is expressed in the human osteoblast-like cell line, MG-63, which has recently been reported by others not to express this receptor. 2) We investigated whether the CaR, if present in MG-63 cells, is functionally active, since most previous studies have not proven the role of the CaR in mediating known actions of Cao 2+ on osteoblast-like cells. We used immunocytochemistry and Western blotting with the specific, affinity-purified anti-CaR antiserum 4637 as well as Northern blot analysis and RT-PCR using a riboprobe and PCR primers specific for the human CaR, respectively, to show readily detectable CaR protein and mRNA expression in MG-63 cells. Finally, we employed the patch-clamp technique to show that an elevation in Cao 2+ as well as the specific, allosteric CaR activator NPS R-467 (0.5 μM), but not its less active stereoisomer NPS S-467 (0.5 μM), activate an outward K+ channel in MG-63 cells, strongly suggesting that the CaR in MG-63 cells is not only expressed but is functionally active.

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Role of the calcium-sensing receptor in extracellular calcium homeostasis

Best Practice & Research Clinical Endocrinology & Metabolism ◽

10.1016/j.beem.2013.02.006 ◽

2013 ◽

Vol 27 (3) ◽

pp. 333-343 ◽

Cited By ~ 127

Author(s):

Edward M. Brown

Keyword(s):

Calcium Homeostasis ◽

Extracellular Calcium ◽

Calcium Sensing Receptor ◽

Calcium Sensing

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Epidermal Keratinocyte Differentiation is Disrupted in Mice Lacking The Full Length Extracellular Calcium-Sensing Receptor

Microscopy and Microanalysis ◽

10.1017/s1431927600007819 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 185-186

Author(s):

László G. Kömüves ◽

Jonathan D. Harris ◽

Chrystal Ho ◽

Daniel D. Bikle

Keyword(s):

In Situ Hybridization ◽

Knockout Mice ◽

Ion Homeostasis ◽

Extracellular Calcium ◽

Full Length ◽

Keratinocyte Differentiation ◽

Calcium Sensing Receptor ◽

Calcium Sensing

The importance of the extracellular calcium-sensing receptor (CaR) in the stringent control of extracellular Ca2+ concentration is well established. However, the presence of CaR in tissues not directly involved in regulating mineral ion homeostasis suggests a role for CaR in local regulation of cellular functions. Although extracellular Ca2+ regulates the differentiation of keratinocytes, the role of CaR in the epidermis is not established. In this work using knockout mice lacking full length CaR, we sought to determine the role of CaR in epidermal differentiation.Dorsal skin of Casr−/− knockout mice lacking full length CaR, and Casr+/+ (wild type) control mice, aged 4 to 7 days after birth was fixed in 4% formaldehyde in PBS, and in 2.5% glutaraldehyde and 2% formaldehyde in 0.1 M cacodylate buffer. The samples were embedded in paraffin (for immunohistochemistry and for in situ hybridization) or in Spurr’s or LR White resins. Digoxigenin labeled antisense and sense RNA probes for loricrin and filaggrin were used for in situ hybridization.

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Role of the calcium-sensing receptor in parathyroid gland physiology

AJP Renal Physiology ◽

10.1152/ajprenal.00013.2004 ◽

2004 ◽

Vol 286 (6) ◽

pp. F1005-F1011 ◽

Cited By ~ 94

Author(s):

Randolph A. Chen ◽

William G. Goodman

Keyword(s):

Parathyroid Gland ◽

Calcium Concentration ◽

Physiological Role ◽

Receptor Expression ◽

Calcium Sensing Receptor ◽

Calcium Sensing ◽

Current Review ◽

Recent Developments ◽

Gland Function

The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range. Much has been learned in recent years about the diversity of signal transduction through the CaSR and the various factors that affect receptor expression. Beyond its classic role as a determinant of calcium-regulated PTH secretion, signaling through the CaSR also influences both gene transcription and cell proliferation in parathyroid cells. The CaSR thus serves a broad physiological role by integrating several distinct aspects of parathyroid gland function. The current review summarizes recent developments that enhance our understanding of the CaSR and its fundamental importance in parathyroid gland physiology.

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