• 1
    Brown EM, Gamba G, Riccardi D, et al. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature. 1993;366:575580.
  • 2
    Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev. 2001;81:239297.
  • 3
    Pollak MR, Brown EM, Chou YH, et al. Mutations in the human Ca2+-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell. 1993;75:12971303.
  • 4
    Chang W, Tu C, Chen TH, et al. Expression and signal transduction of calcium-sensing receptors in cartilage and bone. Endocrinology. 1999;140:58835893.
  • 5
    Dvorak MM, Siddiqua A, Ward DT, et al. Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. Proc Natl Acad Sci USA. 2004;101:51405145.
  • 6
    Kanatani M, Sugimoto T, Kanzawa M, Yano S, Chihara K. High extracellular calcium inhibits osteoclast-like cell formation by directly acting on the calcium-sensing receptor existing in osteoclast precursor cells. Biochem Biophys Res Commun. 1999;261:144148.
  • 7
    Yamaguchi T, Chattopadhyay N, Kifor O, Butters RR Jr, Sugimoto T, Brown EM. Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells. J Bone Miner Res. 1998;13:15301538.
  • 8
    Yamaguchi T, Chattopadhyay N, Kifor O, et al. Expression of extracellular calcium-sensing receptor in human osteoblastic MG-63 cell line. Am J Physiol Cell Physiol. 2001;280:C38293.
  • 9
    Yamaguchi T, Chattopadhyay N, Kifor O, Brown EM. Extracellular calcium (Ca2+(o))-sensing receptor in a murine bone marrow-derived stromal cell line (ST2): potential mediator of the actions of Ca2+(o) on the function of ST2 cells. Endocrinology. 1998;139:35613568.
  • 10
    Kameda T, Mano H, Yamada Y, et al. Calcium-sensing receptor in mature osteoclasts, which are bone resorbing cells. Biochem Biophys Res Commun. 1998;245:419422.
  • 11
    Mentaverri R, Yano S, Chattopadhyay N, et al. The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis. FASEB J. 2006;20:25622564.
  • 12
    Yamauchi M, Yamaguchi T, Kaji H, Sugimoto T, Chihara K. Involvement of calcium-sensing receptor in osteoblastic differentiation of mouse MC3T3-E1 cells. Am J Physiol Endocrinol Metab. 2005;288:E60816.
  • 13
    Chang W, Tu C, Chen TH, Bikle D, Shoback D. The extracellular calcium-sensing receptor (CaSR) is a critical modulator of skeletal development. Sci Signal. 2008;1: ra1.
  • 14
    Garner SC, Pi M, Tu Q, Quarles LD. Rickets in cation-sensing receptor-deficient mice: an unexpected skeletal phenotype. Endocrinology. 2001;142:39964005.
  • 15
    Ho C, Conner DA, Pollak MR, et al. A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat Genet. 1995;11:389394.
  • 16
    Kos CH, Karaplis AC, Peng JB, et al. The calcium-sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone. J Clin Invest. 2003;111:10211028.
  • 17
    Sun W, Sun W, Liu J, et al. Alterations in phosphorus, calcium and PTHrP contribute to defects in dental and dental alveolar bone formation in calcium-sensing receptor-deficient mice. Development. 2010;137:985992.
  • 18
    Reeve J. PTH: a future role in the management of osteoporosis? J Bone Miner Res. 1996;11:440445.
  • 19
    Girotra M, Rubin MR, Bilezikian JP. Anabolic skeletal therapy for osteoporosis. Arq Bras Endocrinol Metabol. 2006;50:745754.
  • 20
    Hodsman AB, Fraher LJ, Watson PH, et al. A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 1997;82:620628.
  • 21
    Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone density in men with osteoporosis. J Bone Miner Res. 2003;18:917.
  • 22
    Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:14341441.
  • 23
    Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem. 2003;278:5025950272.
  • 24
    Zaidi M. Skeletal remodeling in health and disease. Nat Med. 2007;13:791801.
  • 25
    Heaney RP. Calcium needs of the elderly to reduce fracture risk. J Am Coll Nutr. 2001;20 (2 Suppl): 192S197S.
  • 26
    Prince RL, Devine A, Dhaliwal SS, Dick IM. Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med. 2006;166:869875.
  • 27
    Shea B, Wells G, Cranney A, et al. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev. 2004; CD004526.
  • 28
    Cao G, Gu Z, Ren Y, et al. Parathyroid hormone contributes to regulating milk calcium content and modulates neonatal bone formation cooperatively with calcium. Endocrinology. 2009;150:561569.
  • 29
    Miao D, He B, Karaplis AC, Goltzman D. Parathyroid hormone is essential for normal fetal bone formation. J Clin Invest. 2002;109:11731182.
  • 30
    Xue Y, Zhang Z, Karaplis AC, Hendy GN, Goltzman D, Miao D. Exogenous PTH-related protein and PTH improve mineral and skeletal status in 25-hydroxyvitamin D-1alpha-hydroxylase and PTH double knockout mice. J Bone Miner Res. 2005;20:17661777.
  • 31
    Xue Y, Karaplis AC, Hendy GN, Goltzman D, Miao D. Exogenous 1,25-dihydroxyvitamin D3 exerts a skeletal anabolic effect and improves mineral ion homeostasis in mice that are homozygous for both the 1alpha-hydroxylase and parathyroid hormone null alleles. Endocrinology. 2006;147:48014810.
  • 32
    Miao D, Li J, Xue Y, Su H, Karaplis AC, Goltzman D. Parathyroid hormone-related peptide is required for increased trabecular bone volume in parathyroid hormone-null mice. Endocrinology. 2004;145:35543562.
  • 33
    Miao D, Bai X, Panda D, McKee M, Karaplis A, Goltzman D. Osteomalacia in hyp mice is associated with abnormal phex expression and with altered bone matrix protein expression and deposition. Endocrinology. 2001;142:926939.
  • 34
    Miao D, He B, Lanske B, et al. Skeletal abnormalities in Pth-null mice are influenced by dietary calcium. Endocrinology. 2004;145:20462053.
  • 35
    Miao D, Tong XK, Chan GK, Panda D, McPherson PS, Goltzman D. Parathyroid hormone-related peptide stimulates osteogenic cell proliferation through protein kinase C activation of the Ras/mitogen-activated protein kinase signaling pathway. J Biol Chem. 2001;276:3220432213.
  • 36
    Xue Y, Karaplis AC, Hendy GN, Goltzman D, Miao D. Genetic models show that parathyroid hormone and 1,25-dihydroxyvitamin D3 play distinct and synergistic roles in postnatal mineral ion homeostasis and skeletal development. Hum Mol Genet. 2005;14:15151528.
  • 37
    Rodriguez L, Tu C, Cheng Z, et al. Expression and functional assessment of an alternatively spliced extracellular Ca2+-sensing receptor in growth plate chondrocytes. Endocrinology. 2005;146:52945303.
  • 38
    Oda Y, Tu CL, Chang W, et al. The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation. J Biol Chem. 2000;275:11831190.
  • 39
    Tu Q, Pi M, Karsenty G, Simpson L, Liu S, Quarles LD. Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. J Clin Invest. 2003;111:10291037.
  • 40
    VanHouten J, Dann P, McGeoch G, et al. The calcium-sensing receptor regulates mammary gland parathyroid hormone-related protein production and calcium transport. J Clin Invest. 2004;113:598608.
  • 41
    Chattopadhyay N, Yano S, Tfelt-Hansen J, et al. Mitogenic action of calcium-sensing receptor on rat calvarial osteoblasts. Endocrinology. 2004;145:34513462.
  • 42
    Yamaguchi T, Chattopadhyay N, Kifor O, Sanders JL, Brown EM. Activation of p42/44 and p38 mitogen-activated protein kinases by extracellular calcium-sensing receptor agonists induces mitogenic responses in the mouse osteoblastic MC3T3-E1 cell line. Biochem Biophys Res Commun. 2000;279:363368.
  • 43
    Pi M, Faber P, Ekema G, et al. Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J Biol Chem. 2005;280:4020140209.
  • 44
    Pi M, Chen L, Huang MZ, et al. GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS One. 2008;3:e3858.
  • 45
    Wellendorph P, Johansen LD, Jensen AA, et al. No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions. J Mol Endocrinol. 2009;42:21523.
  • 46
    Datta HK, MacIntyre I, Zaidi M. The effect of extracellular calcium elevation on morphology and function of isolated rat osteoclasts. Biosci Rep. 1989;9:747751.
  • 47
    Malgaroli A, Meldolesi J, Zallone AZ, Teti A. Control of cytosolic free calcium in rat and chicken osteoclasts. The role of extracellular calcium and calcitonin. J Biol Chem. 1989;264:1434214347.
  • 48
    Moonga BS, Moss DW, Patchell A, Zaidi M. Intracellular regulation of enzyme secretion from rat osteoclasts and evidence for a functional role in bone resorption. J Physiol. 1990;429:2945.
  • 49
    Zaidi M, Kerby J, Huang CL, et al. Divalent cations mimic the inhibitory effect of extracellular ionised calcium on bone resorption by isolated rat osteoclasts: further evidence for a “calcium receptorJ Cell Physiol. 1991;149:422427.