High Extracellular Calcium Inhibits Osteoclast-like Cell Formation by Directly Acting on the Calcium-Sensing Receptor Existing in Osteoclast Precursor Cells

doi:10.1006/bbrc.1999.0932

Biochemical and Biophysical Research Communications

Volume 261, Issue 1, 22 July 1999, Pages 144-148

https://doi.org/10.1006/bbrc.1999.0932 Get rights and content

Abstract

Although it has recently been suggested that high extracellular calcium ([Ca²⁺]_e) inhibits osteoclast function via a calcium-sensing receptor (CaSR) in mature osteoclasts, the role of CaSR in the regulation of osteoclast formation remains unknown. The present study was performed to investigate whether osteoclast precursor cells possess CaSR and to clarify the possible role of CaSR in the regulation of osteoclast formation. Immunocytochemistry detected CaSR in osteoclast precursor cells derived from spleen cells as well as in osteoblastic MC3T3-E1 cells. The use of reverse-transcription polymerase chain reaction (RT-PCR) with CaSR-specific primers, followed by nucleotide sequencing of the amplified products, also identified CaSR transcripts in osteoclast precursor cells derived from spleen cells as well as in MC3T3-E1 cells. High [Ca²⁺]_e (3 to 5 mM) concentration dependently inhibited 1,25(OH)2D3- or human parathyroid hormone (hPTH) (1–34)-induced osteoclast-like cell (Ocl) formation from osteoclast precursor cells derived from spleen cells. Further, the CaSR agonist neomycin also concentration dependently inhibited 1,25(OH)2D3- or hPTH(1–34)-induced Ocl formation. Moreover, a calcimimetic which mimics or potentiates the effects of [Ca²⁺]_e at the CaSR NPS R-467 (1-100 μM) concentration dependently inhibited Ocl formation stimulated by 1,25(OH)2D3 or hPTH(1–34). These findings first demonstrated that osteoclast precursor cells possess CaSR very similar, if not identical, to those in the parathyroid and kidney. Furthermore, the CaSR in osteoclast precursor cells could play a key role in regulating Ocl formation by sensing local changes in [Ca²⁺]_e at the resorptive sites.

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¹: To whom correspondence should be addressed at Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan. Fax: 078-382-5899 (Japan).

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Regular ArticleHigh Extracellular Calcium Inhibits Osteoclast-like Cell Formation by Directly Acting on the Calcium-Sensing Receptor Existing in Osteoclast Precursor Cells

Abstract

Exp. Cell Res.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Blood

Biochem. Biophys. Res. Commun.

Anal. Biochem.

Clin. Obstet. Gynecol.

Regular Article
High Extracellular Calcium Inhibits Osteoclast-like Cell Formation by Directly Acting on the Calcium-Sensing Receptor Existing in Osteoclast Precursor Cells