Clin Osteol 2007; 12(3): 107-111

Calcitonin and regulation of osteoclastic bone resorptionReview articles

V. Zikán

The calcitonin (CT) gene encodes two polypeptides, CT and a-CT gene-related peptide (aCGRP). CT, a 32-amino-acid-long peptide produced by thyroid C cells, directly inhibits osteoclast function through a high-affinity CT receptor. It is well known that CT levels rise during periods of calcium stress, such as pregnancy, growth, and lactation. The CT/aCGRP-null mouse confirmed that CT pro­ tects the maternal skeleton during lactation, at least in mice. Subjects with CT deficiency as well as CT/aCGRP-null animals were mo­ re responsive to PTH- or vitamin D-induced stimulation. Moreover, the deficiency of CT in the CT/aCGRP-null mouse does result in increased bone resorption with age. However, there is conflicting evidence whether reduced CT secretion with age may contribute to higher bone resorption in humans. In addition, the CT/aCGRP-null mouse showed high bone mass, likely resulting from the central effect of aCGRP. An alternative possibility is that a subtle change in osteoclast function might contribute to preserved bone mass. Ex­ tracellular Ca2+ is a physiologically relevant, direct inhibitor of osteoclastic bone resorption. In vitro studies have shown that CT inhi­ bits Ca2+ sensing. On the other hand, CT loss may enhance Ca2+ sensitivity and therefore preserve bone mass.

Keywords: calcitonin, a -calcitonin gene-related peptide, osteoclasts, bone resorption

Published: December 11, 2007  Show citation

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Zikán V. Calcitonin and regulation of osteoclastic bone resorption. Osteologický bulletin. 2007;12(3):107-111.
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    References

    1. Copp DH, Cameron EC, Cheney BA, Davidson AG, Henze KG. Evidence for cal­ citonin - a new hormone fro crinology. 1962;70:638-649. Go to original source...
    2. Hirsch PF, Lester GE, Talmage RV. Calcitonin, an inigmatic hormone: does have a function? J Musculoskel Neuron Interact. 2001;1:299-305.
    3. Wada S, Udagawa N, Nagata N, Martin TJ, Findlay DM. Physiological levels of calcitonin regulate the mouse osteoclast calcitonin receptor by a protein A-mediated mechanism. Endocrinology. 1996;137:312-320. Go to original source...
    4. Zaidi M, Shankar VS, Adebanjo OA, Lai FA, Pazianas M, Sunavala G, Spielman AI, Rifkin BR. Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations. Am J Physiol. 1996;271:F637-644. Go to original source...
    5. Zaidi M, Moonga BS, Huang CL. Calcium sensing and cell signaling processes in the local regulation of osteoclastic bone resorption. Biol Rev Camb Phi 2004;79:79-100. Go to original source...
    6. Adebanjo OA, Moonga BS, Yamate T, Sun L, Minkin C, Abe E, Zaidi M. Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracel­ lular Ca2+ sensing in the regulation of osteoclastic bone resorption. J Cell Bi 1998;142:1347-1356. Go to original source...
    7. Blair HC, Robinson LJ, Zaidi M. Osteoclast signalling pathways. Biochem Bio­ phys Res Commun. 2005;328:728-38. Go to original source...
    8. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, Iqbal J, Eldeiry L, Rajendren G,Blair HC, Davies TF, Zaidi M. TSH is a negative regulator of skeletal remode­ ling. Cell. 2003;115:151-62. Go to original source...
    9. Dempster DW, Hughes-Begos CE, Plavetic-Chee K, Brandao-Burch A, Cosman F, Nieves J, Neubort S, Lu SS, Iida-Klein A, Arnett T, Lindsay R. Normal human osteoclasts formed from peripheral blood monocytes express PTH type 1 recep­ tors and are stimulated by PTH in the absence of osteoblasts. J Cell Biochem. 2005;95:139-148. Go to original source...
    10. Zaidi M, Shankar VS, Huang CLH, Päzian tonin action. Endocrine J. 1994;2:459-467.
    11. Beaudreuil J, Balasubramanian S, Chenais J, Taboulet J, Frenkian M, Orcel P, J lienne A, Horne WC, de Vernejoul MC, Cressent M. Molecular characterizationof two novel isoforms of the human calcitonin receptor. Gene. 2004;343:143-151. Go to original source...
    12. Nicholson GC, Moseley JM, Sexton PM, Mendelsohn FA, Martin TJ. Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest. 1986;178:355-360. Go to original source...
    13. Chambers TJ and Magnus CJ. Calcitonin alters beahviour of isolated osteocl J Pathol. 1982;136:27-39. Go to original source...
    14. Wada S, Udagawa N, Akatsu T Nagata N, Martin TJ, Findlay DM. Regulation by calcitonin and glucocorticoids of calcitoni teoclasts. Endocrinology. 1997;138:521-529. Go to original source...
    15. Biskobing DM, Fan D. Acid pH increases carbonic anhydrase II and calcitonin ceptor mRNA exprssion in mature osteoclast. Calcif Tissue Int. 2000;67:178-183. Go to original source...
    16. Samura A, Wada S, Suda S, Iitaka M, Katayama S. Calcitonin receptor regulation and responsiveness to calcitonin in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB li stimulating factor. Endocrinology. 2000;141:3774-82. Go to original source...
    17. Cornish J, Callon KE, Bava U, Kamona SA, Cooper GJ, Reid IR. Effects of tonin, amylin, and calcitonin gene-related peptide onosteoclast development. Bone. 2001;29:162-168. Go to original source...
    18. Inoue D, Shih C, Galson DL, Goldring SR, Horne WC, Baron R. Calcitonindependent down-regulation of the mouse C1a calcitonin receptor in cells ofthe osteoc ge involves a transcriptional mechanism. Endocrinology 1999;140:1060-1068. Go to original source...
    19. Wener JA, Gorton SJ, Raisz LG. Escape from inhibition or resorption in cultu of fetal bone treated with calcitonin and parathyroid hormone. Endocrinology 1972;90:752-759. Go to original source...
    20. Wada S, Martin TJ, Findlay DM Homologous regulation of the calcitonin recep­ tor in mouse osteoclast-like cells and human breast cancer T47D cells. Endocri­ nology 1995;136:2611-2621. Go to original source...
    21. Singer FR, Aldred JP, Neer RM, Krane SM, Potts JT Jr, Bloch KJ. An evaluation of antibodies 51:2331-2338.
    22. Zaidi M, Inzerillo AM, Moonga BS, Bevis PJ, Huang CL. Forty years of ca nin - where are we now? A tribute to the work of Iain Macintyre, FRS. Bone. 2002;30:655-663. Go to original source...
    23. Zaidi M, Alam AS, Shankar VS, Bax BE, Moonga BS, Bevis PJ, Pazianas M, Huang CL. A quantitative description of components of in vitro morphometric change in the rat osteoc phys J. 1992;21:349-355. Go to original source...
    24. Yumita S, Nicholson GC, Rowe DJ, Kent GN, Martin TJ. Biphasic effect of cal­ citonin on tartrate-ant acid phosphatase activity in isolated rat osteoclasts. Miner Res. 1991;6:591-597. Go to original source...
    25. Moonga BS, Moss DW, Patchell A, Zaidi M. Intracellular regulation of enzyme secretion from rat osteoclasts and evidence for a functional role in bone resorpti J Physiol Lond. 1990;429:29 45. Go to original source...
    26. Hirsch PF, Voelkel EF, Munson PL Thyrocalcitonin: hypocalcemic hypophosphatemic principle of the thyroid gland. Science 1964;146:412-413. Go to original source...
    27. Talmage RV, VanderWiel CJ, Matthews JL Calcitonin and phosphate. Mol Cell Endocrinol. 1981;24:235-251. Go to original source...
    28. Ikegame M, Ejiri S, Ozawa H. Calcitonin-induced change in serum calcium levels and its relationship to osteoclast morphology and number of calcitonin receptors. Bone. 2004;35:27-33. Go to original source...
    29. Zikan V, Stepan JJ. Plasma type 1 collagen cross-linked C-telopeptide: a ve marker of acute effects of salmon calcitonin on bone resorption. Clin Chim Acta. 2002;316:63-69. Go to original source...
    30. Zikan V, Stepan JJ. Diminished acute response of osteoclasts to calcium load thyroidectomized patients. Calcif Tissue Int. 2004;74:377-381. Go to original source...
    31. Talmage RV, Cooper CW, and Toverud SV. The physioloical significance of cal­ citonin. In: W. Peck (ed) Bone and mineral research annual, Excerpta Medica, Amsterdam, 1983;p 74-83.
    32. Rodriguez M, Felsenfeld AJ, Torres A, Pederson L, Llach F. Calcitonin, an im­ portant factor i Int. 40:219-225.
    33. Blahoš J. Kalcitonin a fosfokalciový metaboliz význam. Thomayerova sbírka, Avicenum, 1974; Praha.
    34. Deftos LJ. Calcitonin. In: Favus MJ (ed.) Primer on the metabolic bone dis and disorders of mineral metabolism. Lippincott-Raven, New York, 1996;p 82-87.
    35. Blahoš J, Adam M, Hulejova H, Spacek P. Kalciovy tolerancni test pri tyreoto koze, Hashimotove tyroiditide a po totalni tyroidektomii. [The calcium tolerance test in thyrotoxicosis, Hashimoto's thyroiditis and after total thyroidectomy]. Lek 1996;42:597-601.
    36. Hoff AO, Catala Lehnen P, Thomas PM, Priemel M, Rueger JM, Nasonkin I, Bra­ dley A, Hughes MR, Ordonez N, Cote GJ, Amling M, Gagel RF.Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. J Clin Invest. 2002;110:1849-1857. Go to original source...
    37. Huebner AK, Schinke T, Priemel M, Schilling S, Schilling AF, Emeson RB, Ru­ eger JM, Amling M. Calcitonin deficiency in mice progressively results in high bone turnover. J Bone Miner Res. 2006;21:1924-1934. Go to original source...
    38. Schinke T, Liese S, Priemel M, Haberland M, Schilling AF, Catala-Lehnen P, charski D, Rueger JM, Gagel RF, Emeson RB, Amling M. Decreased bone for­ mation and osteopenia in mice lacking alpha-calcitonin gene-related peptide. J Bone Miner Res. 2004;19:2049-2056. Go to original source...
    39. Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre­ Medhin S, Galson DL, Zajac JD, Karsenty G. Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol. 2004;164:509-514. Go to original source...
    40. Whitehead M, Lane G, Young O, Campbell S, Abeyasekera G, Hillyard CJ, Ma­ cIntyre I, Phang KG, Stevenson JC.Interrelations of calcium-regulating hormones during normal pregnancy. Br Med J (Clin Res Ed). 1981;283:10-12. Go to original source...
    41. Woodrow JP, Sharpe CJ, Fudge NJ, Hoff AO, Gagel RF, Kovacs CS. Calcitonin plays a critical role in regulati Endocrinology. 2006;147:4010^021. Go to original source...
    42. Silver IA, Murrills RJ, Etherington DJ Microelectrode studies on the acid mic environment beneath adherentmacrophages and osteoclasts. Exp Cell Res. 1988;175:266-276. Go to original source...
    43. Zaidi M, Adebanjo OA, Moonga BS, Sun L, Huang CL.Emerging insight into the role of calcium ions in osteoclast regulation. J Bone Miner Res. 1999;669-674. Go to original source...
    44. Sun L, Iqbal J, Dolgilevich S, Yuen T, Wu XB, Moonga BS, Adebanjo OA, Bevis PJ, Lund F, Huang CL, Blair HC, Abe E, Zaidi M. Disordered osteoclast formati­ on and function in a CD38 (ADP-ribosylcyclase)-deficient mouse establishes an essential role for CD38 in bone resorption. FASEB J. 2003;17:369-375. Go to original source...
    45. Moonga BS, Adebanjo OA, Wang HJ, Li S, Wu XB, Troen B, Inzerillo A, Abe E, Minkin C, Huang CL, Zaidi M. Differential effects of interleukin-6 receptor acti­ vation on intracellularsignaling and bone resorption by isolated rat osteoclasts. J Endocrinol. 2002;173:395 405. Go to original source...
    46. Schlemmer A, Ravn P, Hassager C, Christiansen C Morning or evening adminis­ tration of nasal calcitonin? Effects on biochemical markers ofbone turnover. Bone 1997;20:63-67. Go to original source...
    47. Zaidi M, Moonga BS, Abe E. Calcitonin and bone formation: a knockout full of surprises. J Clin Invest. 2002;110:1769-1771. Go to original source...
    48. Tanko LB, Bagger YZ, Alexandersen P, Devogelaer JP, Reginster JY, Chick R, Olson M, Benmammar H, Mindeholm L, Azria M, Christiansen C. Safety and efficacy of a novel salmon calcitonin (sCT) technology-based oral formulation in healthy postmenopausal women: acute and 3-month effects on biomarkers of bone turnover.J Bone Miner Res. 2004;19:1531-1538. Go to original source...

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