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Critical Reviews™ in Eukaryotic Gene Expression
IF: 2.156 5-Year IF: 2.255 SJR: 0.649 SNIP: 0.599 CiteScore™: 3

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.v13.i24.30
18 pages

In Vitro Studies with the Calcimimetic, Cinacalcet HCl, on Normal Human Adult Osteoblastic and Osteoclastic Cells

Victoria Shalhoub
Department of Metabolic Disorders, 14-1-D, 1 Amgen Center Dr., Thousand Oaks, CA 91320
Mario Grisanti
Department of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA 91320
Jen Padagas
Hematology Department, Amgen, Inc., Thousand Oaks, CA 91320
Sheila Scully
Pathology Department, Amgen, Inc., Thousand Oaks, CA 91320
Alana Rattan
Pathology Department, Amgen, Inc., Thousand Oaks, CA 91320
Meiying Qi
Pathology Department, Amgen, Inc., Thousand Oaks, CA 91320
Brian Varnum
Inflammation Department, Amgen, Inc., Thousand Oaks, CA 91320
Chris Vezina
Inflammation Department, Amgen, Inc., Thousand Oaks, CA 91320
David Lacey
Department of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA 91320
David Martin
Department of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA 91320

ABSTRACT

This study examined whether the calcium-sensing receptor (CaR) is expressed in normal adult human osteoblastic and osteoclastic cells in culture, and whether the calcimimetic, cinacalcet HCl (AMG 073), potentiates the effects of calcium (via CaR, or some other receptor/mechanism). When mouse or human osteoblastic cells were treated with higher concentrations of calcium (6.6 or 8.6 mM in a-MEM/10% FBS) than present in control cultures (1.6 mM), the previously well-documented increase in cell number was demonstrated. Cinacalcet HCl affected cell proliferation of CHO cells transfected with CaR, dose dependently, but had no effect on human or mouse osteoblastic cell proliferation in calcium-containing medium (1.6 or 8.6 mM). To test cinacalcet HCl and calcium on osteoclastic cells, peripheral blood mononuclear cells were cultured in medium containing RANK ligand and M-CSF, supplemented with calcium, and/or cinacalcet HCl. Tartrate-resistant acid phosphatase–positive multinucleated osteoclastic cells on plastic or bone were then counted at 11 and 21 days, respectively. Calcium (greater than 6.0 mM) inhibited osteoclast formation, but cinacalcet HCl (30–1000 nM) had no effect on osteoclastic formation or resorption in the presence of calcium (1.6 or 6.1 mM). RT-PCR did not detect CaR in human, rat, or mouse primary osteoblastic cells and cell lines or osteoclastic cells. In conclusion, these studies indicate that the calcium-induced increase in osteoblastic cell number, and the decrease in formation/function of osteoclastic cells, involves a mechanism or receptor other than CaR. In addition, the calcimimetic agent did not potentiate the effects of calcium on normal adult human bone cells in vitro.


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