Approaches to the Study of the Function and Activity of Bone Regulatory Factors: Established and Potential Methods

  • Joan M. Zanelli
  • Nigel Loveridge
Part of the NATO ASI Series book series (NSSA, volume 184)


The aim of this paper is to review methodological approaches which can either be used to explore the biological activities of bone regulatory factors or be used to measure the amount of a particular factor. The discrimination between explore and measure needs to be made at the outset because practical and scientific considerations for each of these aspects can, at times, appear to be mutually exclusive. This is not intended to be a comprehensive review of methodologies and we do not propose to compare and contrast individual methods for individual substances; instead, we aim to review the rationale of choosing, or developing, appropriate laboratory techniques. We will also propose potential methods, based on in situ biochemistry, which are expected to make a major research contribution to the study of hone regulatory factors. Selection of the most appropriate methodologies requires an objective assessment of the scientific questions to be asked and the relevance of the experimental answers likely to be obtained.


Parathyroid Hormone Acid Phosphatase Activity Mouse Calvaria Familial Hypocalciuric Hypercalcaemia Calciotropic Hormone 
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  1. Allgrove J, Sangal AK, Low DC, Weller PH, Loveridge N 1984. Biologically active parathyroid hormone in familial hypocalciuric hypercalcaemia. Clin Endocrinol 21: 293–298.Google Scholar
  2. Allgrove J, Adami S, Manning RM Chayen J, O’Riordan JLH 1985. Cytochemical bioassay of parathyroid hormone in maternal and cord blood. Arch Dis Chilhood 60: 110–115.Google Scholar
  3. Athanasou NA, Quinn J, McGee J O’D 1988. Immunocytochemical analysis of the human osteoclast: phenotypic relationship to other marrow-derived cells. Bone and Mineral 3: 317–333.Google Scholar
  4. Aubin JE, Heersche JN, Merrilees MJ, Sodek J 1982. Isolation of bone cell clones with differences in growth, hormone responses and extracellular matrix production. J Cell Biol 92: 452–461.PubMedGoogle Scholar
  5. Baumann G, Amburn KD, Buchanan TA. The effect of circulating growth hormone-binding protein on metabolic clearance, distribution and degradation of human growth hormone. J Clin Endocrinol Metab 64: 657–660.Google Scholar
  6. Beresford JN, Gallagher JA, Russell RGG 1986. 1,25 dihydroxyvitamin D3 and human bone derived cells in vitro: effects on alkaline phosphatase type I collagen and proliferation. Endocrinol 119: 1776–1785.Google Scholar
  7. Bergeron JJM, Tchervenkov S, Rouleau MF, Rosenblatt M, Goltzman D 1981. in vivo demonstration of receptors in rat liver to the amino terminal region of parathyroid hormone. Endocrinology 109: 1552–1559.Google Scholar
  8. Benya PD, Shaffer JD 1982. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30: 215–224.PubMedGoogle Scholar
  9. Bianco P, Ballanti P, Bonucci E 1988. Tartrate-resistant acid phosphatase activity in rat osteoblasts and osteocytes. Calcif Tiss Int 43: 167–171.Google Scholar
  10. Boland CJ, Fried RM, Tashjian AH Jr 1986. Measurement of cytosolic free Ca2+ concentration in human and rat osteosarcoma cells: actions of bone resorption-stimulating hormones. Endocrinol 118: 980–989.Google Scholar
  11. Bradbeer JN, Dunham J, Fischer JA, Nagant de Deuxchaisnes C, Loveridge N 1988a. The metatarsal cytochemical bioassay of parathyroid hormone: Validation, specificity and application to the study of pseudohyparathyroidism type I. J Clin Endocrinol Metab, 67: 1237–1243.Google Scholar
  12. Bradbeer JN, Mehdizadeh S, Fraher U, Loveridge N 1988b. Certain vitamin D metabolites potentiate the expression of parathyroid hormone bioactivity J Bone Min Res 3: 47–52.Google Scholar
  13. Bradbeer JN, Reeve J 1987. In situ measurement of osteoblastic alkaline phosphatase activity in relation to the stages of bone formation. Calcif Tiss Int 41 (suppl 2): P95 (abstract).Google Scholar
  14. Braidman IP, Anderson DC, Jones CJP, Weiss JB 1983. Separation of two bone cell populations from fetal rat calvaria and a study of their responses to parathyroid hormone and calcitonin. J Endocrinol 99: 387–399.PubMedGoogle Scholar
  15. Braidman IP, St John JG, Anderson DC, Robertson WR 1986. Effects of physiological concentrations of parathyroid hormone on acid phophatase activity in cultured rat bone cells. J Endocrinol 111: 17–26.PubMedGoogle Scholar
  16. Brown RC, Aston JP, Weeks I, Woodhead JS 1987. Circulating intact parathyroid hormone measured by a two-site immunochemiluminometric assay. J Clin Endocrinol Metab 65: 407–414.PubMedGoogle Scholar
  17. Burtis WJ, Wu T, Bunch C, Wysolmerski JJ, Insogna KL, Weir EC, Broadus AE Stewart AF 1987. Identification of a novel 17,000 dalton PTH-like adenylate cyclasestimulating protein from a tumour associated with humoral hypercalcaemia of malignancy. J Biol Chem 262: 7151–715.PubMedGoogle Scholar
  18. Canalis E 1980. Effect of insulin-like growth factor I on DNA and protein synthesis in cultured rat calvaria. J Clin Invest 66: 709–719.PubMedGoogle Scholar
  19. Canalis E, Raisz LG 1980. Effect of fibroblast growth factor on cultured fetal rat calvaria. Metab Clin Exp 29: 108–114.PubMedGoogle Scholar
  20. Canalis E, Centrella M, McCarthy T 1988. Effects of basic fibroblast growth factor in bone formation in vitro. J Clin Invest 81: 1572–1577.Google Scholar
  21. Chambers DJ, Dunham J, Zanelli JM, Parsons JA, Bitensky L, Chayen J 1978. A sensitive bioassay of parathyroid hormone in plasma. Clin Endocrinol 9: 375–379.Google Scholar
  22. Chambers TJ, Magnus CJ 1982. Calcitonin alters the behaviour of isolated osteoclasts. J Pathol 136: 27–39.PubMedGoogle Scholar
  23. Chambers TJ, McSheehy PMJ, Thompson BM, Fuller K 1985. The effect of calcium regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinol 116: 234–239.Google Scholar
  24. Chambers TJ, Chambers JC, Symonds J, Darby JA 1986. The effect of human calcitonin on the cytoplasmic spreading of rat osteoclasts. J Clin Endocrinol Metab 63: 1080–1085.PubMedGoogle Scholar
  25. Chambers TJ, Fuller KA, Darby JA 1987. Hormonal regulation of acid phosphatase release by osteoclasts disaggregated from noenatal rat bone. J Cell Physiol 132: 90–96.PubMedGoogle Scholar
  26. Chappard D, Alexandre C, Riffat G 1983. Histochemical identification of osteoclasts. Review of current methods and appraisal of a simple procedure for routine diagnosis on undecalcified human iliac bone. Bas Appl Histochem 27: 75–85.Google Scholar
  27. Chayen J 1984. Quantitative cytochemistry: a precise form of cellular biochemistry. Biochem Soc Trans 12: 887–893.PubMedGoogle Scholar
  28. Chayen J, Denby EF 1968. Biophysical Technique as Applied to Cell Biology Methuen, London.Google Scholar
  29. Chayen J, Bitensky L, Butcher RG 1973. Practical Histochemistry. John Wiley, London, pp 234–246.Google Scholar
  30. Chayen J, Daly JR, Loveridge N, Bitensky L 1976. The cytochemical bioassay of hormones. Rec Prog Horm Res 32: 33–79.PubMedGoogle Scholar
  31. Clark CR, Hall MD 1986. Hormone receptor autoradiography: recent developments. Trends Biochem Sci 11: 195–199.Google Scholar
  32. Cole JA, Forte LR, Krause WJ, Thorne PK 1989. Clonal sublines that are morphologically and functionally distinct from parental OK cells. Am J Physiol 256: F672 - F679.PubMedGoogle Scholar
  33. Cornell HJ, Enberg G, Herington AC 1987. Preferential association of the insulin-like growth factors I and II with metabolically inactive and active carrier bound complexed in serum. Biochem J 241: 745–750.PubMedGoogle Scholar
  34. Dabbagh S, Chesney RW, Langer LO, DeLuca HD, Gilbert EF, DeWeerd JH Jr 1984. Renal-nonresponsive, bone responsive pseudohyparathyroidism. Am J Dis Childhood 138: 1030–1033.Google Scholar
  35. Dacke CD, Kenny AD 1973. Avian bioassay method for parathyroid hormone. Endocrinol 92: 463–470.Google Scholar
  36. Davies M, Adams PH, Lumb GA, Berry JL, Loveridge N 1984. Familial hypocalciuric hypercalcaemia: evidence for continued enhanced tubular reabsorption of calcium following total parathyroidectomy. Acta Endocrinologica 106: 499–504.PubMedGoogle Scholar
  37. Davies OK, Hawkins DS, Rubin LP, Posillico JT, Brown EM, Schiff I 1988. Serum parathyroid hormone ( PTH) in pregnant women determined by an immunoradiometric assay for intact PTH. J Clin Endocrinol Metab 67: 850–852.Google Scholar
  38. Demay E, Mitchell J, Goltzman D 1985. Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments. Am J Med 249: E437–445Google Scholar
  39. Dickson IR, Scheven BAA 1989. Regulation of new osteoclast formation by a bone cell-derived macromolecular factor. Biochem Biophys Res Comm 159: 1383–1390.PubMedGoogle Scholar
  40. Dodds RA, Catterall A, Bitensky L, Chayen J 1984. Effects on fracture healing of an antagonist of the vitamin K cycle. Calcif Tiss Int 36: 233–238.Google Scholar
  41. Dodds RA, Catterall A, Bitensky L, Chayen J 1986. Abnormalities in fracture healing induced by vitamin B6-deficiency in rats. Bone 7: 489–495PubMedGoogle Scholar
  42. Dodds RA, Emery RJH, Klenerman L, Bitensky L, Chayen J 1989. Selective depression of particular metabolic activities in cortical osteoblasts at the site of femoral neck fractures. Calcif Tiss Int 44 (suppl): S38 (abstract).Google Scholar
  43. Dunham J, Catterall A, Bitensky L, Chayen J 1983. Metabolic changes in the cells of the callus during fracture healing in the rat. Calcif Tiss Int 35: 56–61.Google Scholar
  44. Drop SLS, Valiquette G, Guyda HJ, Corvol MT, Posner BI 1979. Partial purification and characterisation of a binding protein for insulin-like activity (ILAs) in human amniotic fluid: a possible inhibitor of insulin-like activity. Acta Endocr (Copenh) 90: 505–518.Google Scholar
  45. Eilon B, Raisz LG 1978. Comparison of the effects of stimulators and inhibitors of resorption on the release of lysosomal enzymes and radioactive calcium from fetal bone in culture. Endocrinol 103: 1969–1975.Google Scholar
  46. Finney DJ 1978. Statistical Method in Biological Assay. 3rd Edition. Charles Griffin and Co.Google Scholar
  47. Fuller K, Chambers TJ 1987. Generation of osteoclasts in cultures of rabbit bone marrow and spleen cells. J Cell Physiol 132: 441–452.PubMedGoogle Scholar
  48. Franceschi RT, Romano PR, Park K-Y 1988. Regulation of type I collagen synthesis by 1,25-dihydroxyvitamin D3 in human osteosarcoma cells. J Biol Chem 263: 18938–18945.PubMedGoogle Scholar
  49. Friedenstein A 1980. Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo In: Immunobiology of Bone Marrow (Thierenfelder S Ed), Springer Verlag, Berlin pp 19–29.Google Scholar
  50. Gaillard PJ 1955. Parathyroid gland tissue and bone in vitro. Exp Cell Res (Suppl) 3: 154–169.Google Scholar
  51. Gaillard PJ 1961. Parathyroid and bone tissue in culture. In: The Parathyroids (eds Greep RO, Talmage RV ), Charles C Thomas, Springfield Illinois, pp 20–48.Google Scholar
  52. Gaines-Das RE, Tydeman MS 1978. Interative weighted regression analysis of logit responses. A computer program for analysis of bioassays and immunoassays. Computer Programs in Biomedicine 15: 13–22.Google Scholar
  53. Gibson GJ, Schor SL, Grant ME 1982. Effects of matrix macromolecules on chondrocyte gene expression: synthesis of a low molecular weight collagen species by cells cultured within collagen gels. J Cell Biol 93: 767–774.PubMedGoogle Scholar
  54. Goldhaber P 1958. The effect of hyperoxia on bone resorption in tissue culture. A M A Arch Pathol 66: 635–641.Google Scholar
  55. Goldhaber P 1961. Oxygen dependent bone resorption in tissue culture. In: The Parathyroids (eds Greep RO, Talmage RV ), Charles C Thomas, Springfield Illinois, pp 243–254.Google Scholar
  56. Goltzman D 1978. Examination of the requirement for metabolism of PTH in skeletal tissue before biological action. Endocrinol 102: 1555–1559.Google Scholar
  57. Goltzman D, Callahan EN, Trgear GW, Potts JT Jr 1978. Influence of guanyl nucleotides on parathyroid hormone-stimulated adenylyl cyclase activity in renal cortical membranes. Endocrinol 103: 1352–1360.Google Scholar
  58. Goltzman D, Henderson B, Loveridge N 1980. Cytochemical bioassay of parathyroid hormone: Characteristics of the assay and analysis of circulating hormonal forms. J Clin Invest 65: 1309–1317.Google Scholar
  59. Goltzman D, Stewart AF, Broadus AE 1981. Malignancy associated hypercalcaemia: evaluation with a cytochemical bioassay for parathyroid hormone. J Clin Endocrinol Metab 53: 899–904.PubMedGoogle Scholar
  60. Hammerstrom LE, Hanker JS, Toverud SU 1971. Cellular differences in acid phosphatase isoenzymes in bone and teeth. Clin Orthop 68: 151–167.Google Scholar
  61. Hattersley G, Chambers TJ 1989. Generation of osteoclastic function in mouse bone marrow cultures: Multinuclearity and tartrate-resistant acid phosphatase are unreliable markers for osteoclastic differentiation. Endocrinol 124: 1689–1696.Google Scholar
  62. Horiuchi N, Rosenblatt M 1987. Evaluation of a parathyroid hormone antagonist in an in vivo multiparameter bioassay. Am J Physiol 253: E187 - E192.PubMedGoogle Scholar
  63. Horton MA, Rimmer EF, Moore A, Chambers TJ 1985. On the origin of the osteoclast: the cell surface phenotype of rodent osteoclasts. Calcif Tiss Int 37: 46–50.Google Scholar
  64. Hsu FSF, Pua KH, Nissenson RA 1983. Bioassay of human serum parathyroid hormone using solid phase immunoextraction. Calcif Tiss Int 35: 683–689.Google Scholar
  65. lbbotson KJ, Roodman GD, McManus LM, Mundy GR 1984. Identification and characterization of osteoclast-like cells and their progenitors in culture of feline marrow mononuclear cells. J Cell Biol 99; 471–480.Google Scholar
  66. Ibbotson KJ, Twardzik DR, D’Souza SM, Hargreaves WR, Todaro GJ, Mundy GR 1985. Stimulation of bone resorption in vitro by synthetic transforming growth factor-alpha. Science 228: 1007–1009.PubMedGoogle Scholar
  67. Jones SJ, Boyde A Ali NN Maconnachie E 1986. Variation in the sizes of resorption lacunae made in vitro. Scanning Electron Microsc 4: 1571–1574.Google Scholar
  68. Kent GN, Dodds RA, Bitensky L, Chayen J, Klenerman L, Watts RWE 1983.Google Scholar
  69. Changes in crystal size and orientation of acidic glycosaminoglycans at the fracture site in fractured necks of femur. J Bone Joint Surg (Br) 65:188–194.Google Scholar
  70. Kent GN, Loveridge N, Reeve J, Zanelli JM 1985. Pharmacokinetics of synthetic parathyroid hormone 1–34 in man measured by cytochemical bioassay and radioimmunoassay. Clin Sci 68: 171–177.PubMedGoogle Scholar
  71. Kidd GS, Schaaf M, Adler RA, Lassman MN, Wray HL 1980. Skeletal responsiveness in pseudohypoparathyroidism: A spectrum of clinical disease. Am J Med 68: 72–77.Google Scholar
  72. Kleinman HK, Luckenbill-Edds L, Cannon FW, Sephel GC 1987. Use of extracellular matrix components for cell culture. Anal Biochem 166: 1–13.PubMedGoogle Scholar
  73. Knauer DJ, Smith GL 1980. Inhibition of biological activity of multiplication stimulating activity by binding to its carrier protein. Proc Natl Acad Sci USA 77: 7252–7256.PubMedGoogle Scholar
  74. Kumar MA, Slack E, Edwards A, Soliman HA, Baghdiantz A, Foster GV, McIntyre I 1965. A biological assay for calcitonin. J Endocrinol 33: 469–475.PubMedGoogle Scholar
  75. Kremer R, Bennet HPJ, Mitchell J, Goltzman D 1982. Characterisation of rabbit renal receptor for native parathyroid hormone employing a radioligand purified by reverse phase liquid chromatography. J Biol Chem 257: 14048–14054.PubMedGoogle Scholar
  76. Lane EA, Zanelli JM 1988. Tumour factors associated with the humoral hypercalcaemia of malignancy - acute hypercalcaemic activity of synthetic fragments of parathyroid hormone related peptide. J Endocrinol 119 (suppl) 149 (abstract).Google Scholar
  77. Lindahi AW, Elting J, Elks J, Roos BA 1983. Estimation of biologically active intact parathyroid hormone in normal and hyperparathyroid sera by sequential N-terminal immunoextraction and mid-region immunoassay. J Clin Endocrinol Metab 57: 1007–1014.Google Scholar
  78. Lomri A, Marie PJ 1988. Effect of parathyroid hormone and forskolin on cytoskeletal protein synthesis in cultured mouse osteoblastic cells. Biochim Biophys Acta 970: 333–342.PubMedGoogle Scholar
  79. Loveridge N 1983. The technique of cytochemical bioassay. In: Cytochemical Bioassays: Techniques and Clinical Applications. (eds Chayen J, Bitensky L ), Marcel Dekker, New York pp 45–82.Google Scholar
  80. Loveridge N, Farquharson C 1989. A novel approach to the assay of the skeletal activities of growth factors and calciotropic hormones. J Bone Min Res in press (abstract).Google Scholar
  81. Loveridge N, Fischer JA, Nagant de Deuxchaisnes C, Dambacher MA, Werder E, Devogelaer J-P, De Meyer R, Bitensky L, Chayen J 1982. Inhibition of cytochemical bioactivity of parathyroid hormone by plasma in pseudohypoparathyroidism type I. J Clin Endocrinol Metab 54: 1274–1275.PubMedGoogle Scholar
  82. Loveridge N, Kent GN, Heath DA, Jones EL 1985. Parathyroid hormone-like bioactivity in a patient with severe osteitis fibrosa cystica due to malignancy: renotropic actions of a tumour extract as assessed by cytochemical bioassay. Clin Endocrinol 22: 135–146.Google Scholar
  83. Loveridge N, Tschopp F, Born W, Devogelaer J-P, Nagant de Deuxchaisnes C, Fischer JA 1986a. Separation of inhibitory activity from biologically active parathyroid hormone in patients with pseudohypoparathyroidism type I. Biochim Biophys Acta, 889: 117–122.PubMedGoogle Scholar
  84. Loveridge N, Fischer JA, Devogelaer J-P, Nagant de Deuxchaisnes C 1986b. Suppression of parathyroid hormone inhibitory activity of plasma in pseudohyoparathyroidism type I by IV calcium. Clin Endocrinol 24: 549–554.Google Scholar
  85. Loveridge N, Caple IW, Rodda C, Martin TJ, Care AD 1988. Further evidence for a parathyroid hormone-related protein in fetal parathyroid glands of sheep. Quart J Exp Physiol 73: 781–784.Google Scholar
  86. Luben RA, Wong GL, Cohn DV 1976. Biochemical characterization with parathormone and calcitonin of isolated bone cells: provisional identification of osteoclasts and osteoblasts. Endocrinol 99: 526–534.Google Scholar
  87. Lundy MW, Lau K-HW, Blair HC, Baylink DJ 1988. Chick osteoblasts contain fluoride sensitive acid phosphatase activity. J Histochem Cytochem 36: 1175–1180.PubMedGoogle Scholar
  88. MacDonald BR, Gallagher JA, Anfelt-Ronne I, Beresford JN, Gowen M, Russell RGG 1984. Effects of bovine parathyroid hormone and 1,25 dihydroxyvitamin D3 on the production of prostaglandins by cells derived from human bone. FEBS Letts 169: 49–52.Google Scholar
  89. MacDonald BR, Gallagher JA, Russell RGG 1986. Parathyroid hormone stimulates the proliferation of cells derived from human bone. Endocrinol 118: 2445–2449.Google Scholar
  90. MacDonald BR, Takahashi N, McManus LM, Holahan J, Mundy GR, Roodman GD 1987. Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. Endocrinol 120: 2326–2333.Google Scholar
  91. Majeska RJ, Rodan SB, Rodan GA 1980. Parathyroid hormone responsive clonal cell line from rat osteosarcoma. Endocrinol 107: 1494–1503.Google Scholar
  92. Martin KJ, Hruska KA, Freitag JJ, Klahr S, Slatopolsky E 1979. The peripheral metabolism of parathyroid hormone. N Eng J Med 301: 1092–1095.Google Scholar
  93. Martin TJ, Ingelton PM, Underwood JCE, Michelangeli VP, Henk NH, Melick RA 1976. Nature 260: 436–438.PubMedGoogle Scholar
  94. McKee MD, Murray TM 1985. Binding of intact parathyroid hormone to chicken renal membranes: evidence for a second binding site with carboxy-terminal specificity. Endocrinol 11.7: 1930–1939.Google Scholar
  95. McSheehy PMJ, Chambers TJ 1986. Osteoblastic cells mediate osteoclastic responsiveness to parathyroid hormone. Endocrinol 118: 824–828.Google Scholar
  96. Miller SC 1985. The rapid appearance of acid phosphatase activity at the developing ruffled border of parathyroid hormone activated medullary bone osteoclasts. Calcif Tiss Int 37: 526–529.Google Scholar
  97. Minkin C 1982. Bone acid phosphatase: tartrate resistant acid phosphatase as a marker for of osteoclast function. Calcif Tiss Int 34: 285–290.Google Scholar
  98. Moseley JM, Kubota M, Diefenbach-Jagger H, Wettenhal REH, Kemp BE, Suva LJ, Rodda CP, Ebeling PR, Hudson PJ, Zajac JD, Martin TJ 1987. Parathyroid hormone-related protein purified from a human lung cancer cell line. Proc Acad Sci USA 84: 5048–5052.Google Scholar
  99. Mostafa YA, Meyer RA, Latorraca R 1982. A simple and rapid method for osteoclast indentification using a histochemical method for acid phosphatase. Histochem J 14: 409–413.PubMedGoogle Scholar
  100. Munson PL 1961. Biological assay of parathyroid hormone. In: The Parathyroids, (eds Greep RO, Talmage RV ), Charles C Thomas, Springfield, Illinois. pp 94–113.Google Scholar
  101. Murray TM, Rao LG, Muzaffar SA, Ly H 1989. Human parathyroid hormone carboxylterminal peptide (53–84) stimulates alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma cells in vitro. Endocrinol 124: 1097–1099.Google Scholar
  102. Nagant de Deuxchaisnes C, Fischer JA, Dambacher MA, Devogelaer J-P, Arber CE, Zanelli JM, Parsons JA, Loveridge N, Bitensky L, Chayen J 1981. Dissociation of parathyroid hormone bioactivity and immunoreactivity in pseudohypoparathyroidism type I. J Clin Endocrinol Metab 53: 1105–1109PubMedGoogle Scholar
  103. Nasr LB, Monet J-D, Lucas PA 1988. Rapid (10 minute) stimulation of rat duodenal alkaline phosphatase activity by 1,25-dihydroxyvitamin D3. Endocrinol 123: 1778–1782.Google Scholar
  104. Nemere I, Yoshimoto Y, Norman AW 1984. Calcium transport in perfused duodena from normal chicks: Enhancement within fourteen minutes of exposure to 1,25-dihydroxy-vitamin D3. Endocrinol 115: 1476–1483.Google Scholar
  105. Niepel B, Radeke H, Atkinson MJ, Juppner H, Hesch RD 1983. A homologous biological assay for parathyroid hormone in human serum. J Immunoassay 4: 21–47.PubMedGoogle Scholar
  106. Nijweide PJ, Vrijheid-Lammers T, Mulder RJP, Blok J 1985. Cell surface antigens on osteoclasts and related cells in the quail studied with monoclonal antibodies. Histochemistry 83: 315–324.PubMedGoogle Scholar
  107. Nishimoto SK, Price PA 1980. Secretion of the vitamin K dependent protein of bone by rat osteosarcoma cells: evidence for an intracellular precursor. J Biol Chem 255: 6579–6583.PubMedGoogle Scholar
  108. Nissenson RA, Abbot SR, Teitelbaum AP, Clark OH, Arnaud CD 1981. Endogenous biologically active human parathyroid hormone: measurement by a guanyl nucleotide-amplified adenylate cyclase assay. J Clin Endocrinol Metab 46: 604–612.Google Scholar
  109. Noda M, Rodan GA 1986a. Type ß transforming growth factor inhibits proliferation and expression of alkaline phosphatase in murine osteoblast-like cells. Biochem Biophys Res Commun 140: 56–65.PubMedGoogle Scholar
  110. Noda M, Rodan GA 1986b. Type-beta transforming growth factor ( TGF-beta) regulation of alkaline phosphatase expression and other phenotype-related messenger RNA’s in osteoblastic rat osteosarcoma cells. J Cell Physiol 133: 426–437.Google Scholar
  111. Orrefo ROC, Mundy GR, Seyedin SM, Bonewald LF 1989. Activation of the bone-derived latent TGF-ß complex by isolated osteoclasts. Biochem Biophys Res Commun 158: 817–824.Google Scholar
  112. Oursler MJ, Bern LV, Clevinger B, Osdoby P 1985. Identification of osteoclastspecific monoclonal antibodies. J Cell Biol 100: 1592–1600.PubMedGoogle Scholar
  113. Owen M 1985. Lineage of osteogenic cells and their relationship to the stromal system. In: Bone and Mineral Research Ann Vol 3 ( Peck W ed), Excerpta Medica, Amsterdam pp 1–25.Google Scholar
  114. Parsons JA, Reit B, Robinson CJ 1973. A bioassay for parathyroid hormone using chicks. Endocrinol 92: 454–462.Google Scholar
  115. Parsons JA, Rafferty B, Gray D, Reit B, Zanelli JM, Keutman HT, Tregear GW, Callahan EN, Potts JT Jr 1975. Pharmacology of parathyroid hormone and some of its fragments and analogues. In: Calcium Regulating Hormones (eds Talmage RV, Owen M, Parsons JA ), Excerpta Medica, Amsterdam, pp 33–39.Google Scholar
  116. Partridge NC, Frampton RJ, Eisman JA, Michelangeli VP, Elms E, Bradley TR, Martin TJ 1980. Receptors for 1,25(OH), vitamin D3 enriched in clonal osteoblast-like rat osteogenic osteosarcoma cells. FEBS Letts 115: 139–142.Google Scholar
  117. Partridge NC, Alcorn D, Michelangeli VP, Kemp BE, Ryan GB, Martin TJ 1981. Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells Enodocrinol 108: 213–219.Google Scholar
  118. Pearse AGE 1980. Histochemistry: Theorectical and Applied, Vol 1, 4th edition, Churchill-Livingstone, LondonGoogle Scholar
  119. Pfeilschifter J, Seyedin SM, Mundy GR 1988. Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures. J Clin Invest 82: 680–685.PubMedGoogle Scholar
  120. Pfeilschifter J, D’Souza SM, Mundy GR 1987. Effects of transforming growth factor-13 on osteoblastic osteosarcoma cells. Endocrinol 121: 212–218.Google Scholar
  121. Pharoah MJ, Heersche JNM 1985. 1,25 dihydroxyvitamin D3 causes an increase in the number of osteoclast-like cells in cat bone marrow cultures. Calcif Tiss Int 37: 276–281.Google Scholar
  122. Raisz LG. 1963. Stimulation of bone resorption by parathyroid hormone in tissue culture. Nature 197: 1015.PubMedGoogle Scholar
  123. Raisz LG 1965. Bone resorption in tissue culture. Factors influencing the response to parathyroid hormone. J Clin Invest 44: 103–106.PubMedGoogle Scholar
  124. Rao LG, Murray TM 1985. Binding of intact parathyroid hormone to rat osteosarcoma cells: major contribution of binding sites for the carboxy-terminal region of the hormone. Endocrinology 117: 1632–1638.PubMedGoogle Scholar
  125. Reynolds JJ, Dingle JT 1970. A sensitive in vitro method for studying the induction and inhibtion of bone resorption. Calcif Tiss Res 4: 339–349.Google Scholar
  126. Rico AG, Bernard P, Braun JP, Burgat-Sacaze V 1980. Whole body autoradiography in metabolic studies of drugs and toxicants. Adv Vet Sci Comp Med 24: 291–311.PubMedGoogle Scholar
  127. Robertson WR, Lambert A, Loveridge N (1987). The role of modern in clinical endocrinolgy. Clin Endocrinol 27: 259–278.Google Scholar
  128. Rodan GA, Martin TJ 1981. Role of osteoblasts in hormonal control of bone resorption: a hypothesis. Calcif Tiss Int 33: 349–351.Google Scholar
  129. Rodan GA, Rodan SB 1984. Expression of the osteoblastic phenotype. In; Bone and Mineral Research Annual vol 2 (Peck WA ed), Elsevier, Amsterdam, pp 244–285. Rosen DM, Stempien SA, Thompson AY, Seyedin SM 1988. Transforming growth factor-beta modulates the expression of osteoblast and chondroblast phenotypes in vitro. J Cell Physiol 134: 337–346.Google Scholar
  130. Rosenblatt M, Callahan EN, Mahaffey JE, Pont A, Potts JT Jr 1977. Parathyroid hormone inhibitors. Design, synthesis and biological evaluation of hormone analogues. J Biol Chem 252: 5847–5851.Google Scholar
  131. Rouleau MF, Warshawsky H, Goltzman D 1986. Parathyroid hormone binding in vivo to renal, hepatic and skeletal tissues of the rat using a radioautographic approach. Endocrinol 118: 919–931.Google Scholar
  132. Rouleau MF, Mitchell J, Goltzman D 1988. in vivo distribution of parathyroid a predominant osseous target cell is not -191.Google Scholar
  133. Quantitative cytochemical responses to rat kidney and bone cells. Mol Cell Loveridge N 1987. PTH bioactivity inGoogle Scholar
  134. Seshadri MS, Chan YL, Wilkinson MR, Mason RS Posen S 1985b. Some problems associated with adenylate cyclase bioassays for parathyroid hormone. Clin Sci 68: 311–319.PubMedGoogle Scholar
  135. Skerry TM, Bitensky L, Chayen J, Lanyon LE 1988. Loading related reorientation of bone proteoglycan in vivo. Strain memory in bone tissue? J Orthop Res 6: 547–551.PubMedGoogle Scholar
  136. Sporn MB, Roberts AB, Wakefield LM, deCrombrugghe B 1987. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 33: 105: 1039–1045.Google Scholar
  137. Stamp TCB, Jenkins MV, Loveridge N, Saphier PW, Katakity M, MacArthur S 1988. Fluoride therapy in osteoporosis: acut effects on parathyroid and mineral homeostasis. Clin Sci 75: 143–146.PubMedGoogle Scholar
  138. Stewart AF, Insogna KL, Goltzman D, Broadus AE 1983. Identification of adenylate cyclase and cytochemical glucose 6-phophate dehydrogenase stimulating activity in extracts of tumours from patients with humoral hypercalcaemia of malignancy. Proc Natl Acad Sci USA 80: 1451–1458.Google Scholar
  139. Strewler GJ, Stern PH, Jacobs JW, Eveloff J, Klein RF, Leung SC, Rosenblatt M, Nissenson R 1987. Parathyroid hormone-like protein from human renal carcinoma: structural and functional homology with parathyroid hormone. J Clin Invest 80: 1803–1805.PubMedGoogle Scholar
  140. Scheven BAA, Kawilarang-de Hass EWM, Wassenaar A-M, Nijweide PJ 1986a. Differentiation kinetics of osteoclasts in the periosteum of embryonic bones in vivo and in vitro. Anat Rec 214: 418–423.PubMedGoogle Scholar
  141. Scheven BAA, Visser JWM, Nijweide PJ 1986b. in vitro osteoclast generation from different bone marrow fractions, including a highly enriched haematopoietic stem cell population. Nature 321: 79–81.Google Scholar
  142. Scheven BAA, Hamilton NJ 1990.. Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms. Bone in pressGoogle Scholar
  143. Seshadri MS, Chan YL, Wilkinson MR, Mason RS Posen S 1985a. An adenylate cyclase bioassay for parathyroid hormone: some clinical experiences. Clin Sci 68: 321–326.PubMedGoogle Scholar
  144. Sudo H, Kodama H, Amagai Y, Yamamoto S Kasai S 1983. in vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol 96: 191–198.Google Scholar
  145. Tashjian AH, Levine L 1978. Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria. Biochem Biophys Res Commun 85: 966–975.PubMedGoogle Scholar
  146. Tashjian AH, Hohman EL, Antoniades HN, Levine L 1982. Platelet-derived growth factor stimulates bone resorption via a prostaglandin-mediated mechanism. Endocrinol 111: 118–124.Google Scholar
  147. Tashjian AH, Voekel EF, Lazzaro M, Goad D, Bosma T, Levine L 1987. Tumour necrosis factor a (cachechtin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism. Endocrinol 120: 2029–2036.Google Scholar
  148. Tashjian AH, Voekel EF, Lazzaro M, Singer FR, Roberts AB, Derynck R, Winkler ME, Levine L 1985. a and ß human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria. Proc Natl Acad Sci USA 82: 4535–4538.Google Scholar
  149. Testa NG, Allen TD Lajtha LG, Onions D, Jarret O 1981. Generation of osteoclasts in vitro. J Cell Sci 47: 127–137.PubMedGoogle Scholar
  150. Teitelbaum AP, Strewler GJ 1984. Parathyroid hormone receptors coupled to cyclic adenosine monophosphate formation in an established renal cell line. Endocrinol 114: 980–986.Google Scholar
  151. Thiede MA, Rodan GA 1988. Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Science 242: 278–280.PubMedGoogle Scholar
  152. Ullberg S 1977. The technique of whole body autoradiography. Cryosectioning of large specimens. Science Tools, LKB Instrument Journal 2–29.Google Scholar
  153. Vaes G 1968. On the mechanisms of bone resorption. The action of parathyroid hormone on the excretion and synthesis of lysosomal enzymes and on the extracellular release of acid by bone cells. J Cell Biol 39: 676–697.PubMedGoogle Scholar
  154. Van de Velde JP, Loveridge N, Vermeiden JPW 1984. Parathyroid hormone responses to calcium stress during egg-shel calcification. Endocrinol 150: 1901–1904Google Scholar
  155. Van de Wijngaert FP, Tas MC, Burger EH 1987. Characteristics of osteoclast precursor-like cells grown from mouse bone marrow. Bone and Mineral 3: 111–123.PubMedGoogle Scholar
  156. Warshowsky H, Goltzman D, Rouleau MF, Bergeron JJM 1980. Direct in vivo demonstration by radioautography of specific binding sites for calcitonin in skeletal and renal tissues of the rat. J Cell Biol 85: 682–694.Google Scholar
  157. Webber D, Braidman IP, Robertson WR, Anderson DC 1989. The effect of tartrate on bone cell acid phosphatase; a quantitative cytochemical study. J Bone Min Res in press.Google Scholar
  158. Wong GL 1984. Paracrine interactions in bone-secreted products of osteoblasts permit osteoclasts to respond to parathyroid hormone. J Biol Chem 259: 4019–4022.PubMedGoogle Scholar
  159. Wong GL, Cohn DV 1974. Separation of parathyroid hormone and calcitonin sensitive cells from non-responsive bone cells. Nature 252: 713–715.PubMedGoogle Scholar
  160. Wong GL, Cohn DV 1975. Target cells in bone for parathormone and calcitonin are different: enrichment for each cell type by sequential digestion of mouse calvaria and selective adhesion to polymeric surfaces. Proc Natl Acad Sci USA 72: 3167–3170.PubMedGoogle Scholar
  161. Wergedal JE, Baylink DJ 1969. Distribution of acid and alkaline phosphatase activity in undemineralised sections of the rat tibial diaphysis. J Histochem Cytochem 17: 799–806.PubMedGoogle Scholar
  162. Zanelli JM, Lane E, Kimura T, Sakakibara S 1985a. Biological activities of synthetic human parathyroid hormone (PTH) 1–84 relative to natural bovine 1–84 PTH in two different in vivo bioassay systems. Endocrinol 117: 1962–1967.Google Scholar
  163. Zanelli JM, Salmon DM, Azria M, Salmon GD 1985b. A rat model for resistance to chronic treatment with salmon calcitonin; application of quantitative cytochemistry. In: Calcitonin 1984. Chemistry, Physiology, Pharmacology, and Clinical Aspects, (ed Pecile A ), Excerpta Medica, Amsterdam, pp 223–230.Google Scholar
  164. Zanelli JM, Lea DJ, Nisbet JA 1969. A bioassay method in vitro for parathyroid hormone. J Endocrinol 43: 33–46.PubMedGoogle Scholar
  165. Zanelli JM, Parsons JA 1980. Bioassay of Parathyroid Hormone. In: Handbuch der inneren Medizin vol lA (eds Kuhlencordt F, Bartelheimer H ), Springer-Verlag, Berlin Heidelberg, New York, pp 599–621.Google Scholar
  166. Zapf J, Schoenle E, Jagers E, Sand I, Froesch ER 1979. Inhibition of the action of non-suppressible insulin-like activity on isolated rat fat cells by binding to its carrier protein. J Clin Invest 63: 1077–1084.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Joan M. Zanelli
    • 1
  • Nigel Loveridge
    • 2
  1. 1.National Institute for Biological Standards and ControlBlanche Lane, South Mimms, Potters BarUK
  2. 2.Bone Growth and Metabolism UnitRowett Research InstituteAberdeenUK

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