Is the calcium receptor a molecular target for the actions of strontium on bone

作者: Edward M. Brown

DOI: 10.1007/S00198-002-1343-6

关键词: Bone cellEndocrinologyMedicineParathyroid chief cellCalcitoninHomeostasisOsteoblastParathyroid hormoneBone resorptionCalcium metabolismInternal medicine

摘要: The extracellular calcium-sensing receptor (CaR) plays key roles in maintaining calcium homeostasis by enabling several of the cells and tissues involved this process to sense small changes Ca(2+)(o) respond with cellular function that will restore its normal level. chief parathyroid gland thyroidal C-cells, for example, decreases increased secretion Ca(2+)(o)-elevating hormone, hormone (PTH), decreased Ca(2+)(o)-lowering calcitonin, respectively. renal distal tubule are likewise capable sensing tubular reabsorption Ca(2+) vice versa, alterations contribute normalization Ca(2+)(o). skeleton also both osteoblasts osteoclasts can Ca(2+)(o), elevations promoting bone formation inhibiting resorption. It has been suggested Sr(2+) could act on via CaR; however, molecular mechanisms through which Sr(2+)(o) exert these actions remain controversial. Therefore, identifying their target(s) would have significant implications treatment loss. Ideally, therapies should simultaneously inhibit resorption while stimulating formation. Administration strontium produces exactly those effects. Previous studies dispersed bovine as well a preliminary study using CaR-transfected Chinese hamster ovary (CHO) indicate is an agonist CaR, albeit slightly lower efficacies potencies than Given distributed preferentially bone, therefore, action divalent cation CaR represents one possible mechanism ranelate, new antiosteoporotic drug, exerts it skeletal vivo.

参考文章(61)
Kausik Ray, Benjamin C. Hauschild, Peter J. Steinbach, Paul K. Goldsmith, Omar Hauache, Allen M. Spiegel, Identification of the Cysteine Residues in the Amino-terminal Extracellular Domain of the Human Ca2+ Receptor Critical for Dimerization: IMPLICATIONS FOR FUNCTION OF MONOMERIC Ca2+RECEPTOR * Journal of Biological Chemistry. ,vol. 274, pp. 27642- 27650 ,(1999) , 10.1074/JBC.274.39.27642
M Bai, Structure and function of the extracellular calcium-sensing receptor (Review). International Journal of Molecular Medicine. ,vol. 4, pp. 115- 140 ,(1999) , 10.3892/IJMM.4.2.115
Brian W. Bapty, Long-jun Dai, Gordon Ritchie, Frank Jirik, Lucie Canaff, Geoffrey N. Hendy, Gary A. Quamme, Extracellular Mg2+- and Ca2+-sensing in mouse distal convoluted tubule cells Kidney International. ,vol. 53, pp. 583- 592 ,(1998) , 10.1046/J.1523-1755.1998.00790.X
Min Pi, Todd K. Hinson, L. Darryl Quarles, Failure to detect the extracellular calcium-sensing receptor (CasR) in human osteoblast cell lines Journal of Bone and Mineral Research. ,vol. 14, pp. 1310- 1319 ,(1999) , 10.1359/JBMR.1999.14.8.1310
Masanori Kanatani, Toshitsugu Sugimoto, Michiko Kanzawa, Shozo Yano, Kazuo Chihara, High Extracellular Calcium Inhibits Osteoclast-like Cell Formation by Directly Acting on the Calcium-Sensing Receptor Existing in Osteoclast Precursor Cells Biochemical and Biophysical Research Communications. ,vol. 261, pp. 144- 148 ,(1999) , 10.1006/BBRC.1999.0932
Pierre J. Marie, Monique Hott, Dominique Modrowski, Cinderella De Pollak, Joel Guillemain, Pascale Deloffre, Yannis Tsouderos, An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient Rats Journal of Bone and Mineral Research. ,vol. 8, pp. 607- 615 ,(2005) , 10.1002/JBMR.5650080512
John M. Arthur, Martha S. Lawrence, Cameron R. Payne, Madhavi J. Rane, Kenneth R. McLeish, The Calcium-Sensing Receptor Stimulates JNK in MDCK Cells Biochemical and Biophysical Research Communications. ,vol. 275, pp. 538- 541 ,(2000) , 10.1006/BBRC.2000.3226
Mone Zaidi, Olugbenga A Adebanjo, Baljit S Moonga, Li Sun, Christopher L‐H Huang, None, Emerging Insights into the Role of Calcium Ions in Osteoclast Regulation Journal of Bone and Mineral Research. ,vol. 14, pp. 669- 674 ,(1999) , 10.1359/JBMR.1999.14.5.669