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IGF System Components and Their Role in Bone Metabolism

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Part of the book series: Contemporary Endocrinology ((COE,volume 17))

Abstract

Bone is a dynamic tissue that is capable of repair after injury and remodeling in response to changes in physical strains that occur throughout life. This regenerative property of the bone is essential for the maintenance of the structural mass, strength, and shape of bone and for fracture healing The volume of bone and ultimately its strength are determined by the balance between two opposing processes, osteoclastic bone resorption and osteoblastic bone formation, that together constitute bone remodeling. The balance may be shifted to favor more formation than resorption, leading to net gain in bone as seen during puberty or during increased mechanical loading. The balance can also be shifted to favor less formation than resorption as seen during disuse or during chronic disease states such as osteoporosis. Studies in a number of laboratories have focused on understanding the regulation of the bone resorption and bone formation processes based on the premise that insights on molecular signaling messenger molecules that are responsible for controlling these two processes could lead to new treatments for osteoporosis. The following section briefly describes the bone cell parameters involved in bone formation and bone resorption processes and the corresponding regulatory signaling molecules that are responsible for regulating these bone cell parameters.

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References

  1. Roodman GD. Advances in bone biology: the osteoclast. Endocr Rev 1996; 17: 308–332.

    PubMed  CAS  Google Scholar 

  2. Aubin JE, Liu F. The osteoblast lineage. In: Bilezikian JP, Raisz LG, Rodan GA, eds. Principles in Bone Biology. Academic Press, San Diego, 1996, pp. 51–68.

    Google Scholar 

  3. Mohan S, Linkhart T, Farley J, Baylink D. Bone-derived factors active on bone cells. Calcif Tissue Int 1984; 36 (Suppl 1): 5139–45.

    Article  Google Scholar 

  4. Mohan S, Jennings JC, Linkhart TA, Baylink DJ. Primary structure of human skeletal growth factor: homology with human insulin-like growth factor-II. Biochim Biophys Acta 1988; 966: 44–55.

    Article  PubMed  CAS  Google Scholar 

  5. Mohan S, Baylink DJ. Bone growth factors. [Review]. Clin Orthop Rel Res 1991; 30–48.

    Google Scholar 

  6. Bautista CM, Mohan S, Baylink DJ. Insulin-like growth factors I and II are present in the skeletal tissues of ten vertebrates. Metab Clin Exp 1990; 39: 96–100.

    Article  PubMed  CAS  Google Scholar 

  7. Canalis E, McCarthy T, Centrella M. Isolation and characterization of insulin-like growth factor I (somatomedin-C) from cultures of fetal rat calvariae. Endocrinology 1988; 122: 22–27.

    Article  PubMed  CAS  Google Scholar 

  8. Canalis E, Pash JM, Verghese S. Skeletal growth factors. Crit Rev Euk Gene Expr 1993; 3: 155–166.

    CAS  Google Scholar 

  9. Conover CA. The role of insulin-like growth factors and binding proteins in bone cell biology. In: Bilezikian JP, Rodan GA, eds. Principles of Bone Biology. Academic Press, San Diego, 1996; pp. 607–618.

    Google Scholar 

  10. Baylink DJ, Finkelman RD, Mohan S. Growth factors to stimulate bone formation. [Review]. J Bone Miner Res 1993; 8 (Suppl 2): S565–72.

    Article  PubMed  Google Scholar 

  11. Shinar DM, Endo N, Halperin D, Rodan GA, Weinreb M. Differential expression of insulin-like growth factor-I (IGF-I) and IGF-II messenger ribonucleic acid in growing rat bone. Endocrinology 1993; 132: 1158–1167.

    Article  PubMed  CAS  Google Scholar 

  12. Malpe R, Baylink DJ, Linkhart TA, Wergedal JE, Mohan S. Insulin-like growth factor (IGF)-I, -II, IGF binding proteins (IGFBP)-3, -4, and -5 levels in the conditioned media of normal human bone cells are skeletal site-dependent. J Bone Miner Res 1997; 12: 423–430.

    Article  PubMed  CAS  Google Scholar 

  13. Mohan S, Bautista CM, Herring SJ, Linkhart TA, Baylink DJ. Development of valid methods to measure insulin-like growth factors-I and -II in bone cell-conditioned medium. Endocrinology 1990; 126: 2534–2542.

    Article  PubMed  CAS  Google Scholar 

  14. Okazaki R, Conover CA, Harris SA, Spelsberg TC, Riggs BL. Normal human osteoblast-cells constitutively express genes for insulin-like growth factors-I and II but transformed human osteoblast cell lines do not. J Bone Miner Res 1995; 10: 788–795.

    Article  PubMed  CAS  Google Scholar 

  15. McCarthy TL, Centrella M, Canalis E. Constitutive synthesis of insulin-like growth factor-II by primary osteoblast-enriched cultures from fetal rat calvariae. Endocrinology 1992; 130: 1303–1308.

    CAS  Google Scholar 

  16. Canalis E. Insulin like growth factors and the local regulation of bone formation. [Review]. Bone 1993; 14: 273–276.

    Article  PubMed  CAS  Google Scholar 

  17. Birnbaum RS, Bowsher RR, Wiren KM. Changes in IGF-I and -II expression and secretion during the proliferation and differentiation of rat osteoblasts. J Endocrinol 1995; 144: 251–259.

    Article  PubMed  CAS  Google Scholar 

  18. Zhang RW, Simmons DJ, Crowther RS, Mohan S, Baylink DJ. Contribution of marrow stromal cells to the regulation of osteoblast proliferation in rats: evidence for the involvement of insulin-like growth factors. Bone Miner 1991; 13: 201–215.

    Article  PubMed  CAS  Google Scholar 

  19. Hayden JM, Hart KA, Baylink DJ, Johnstone D, Thompson G, Mohan S. Basal and regulated secretion of IGF system components differ between human bone marrow stromal cells and normal human osteoblasts. In: 10th International Congress of Endocrinology, San Francisco, CA, June 12–15, 1996 (Abstract).

    Google Scholar 

  20. Cheng SL, Zhang SF, Mohan S, Lecanda F, Fausto A, Hunt AH, Canalis E, Avioli LV. Regulation of IGF-I, IGF-II and their binding proteins in human bone marrow stromal cells by dexamethasone. J Cell Biochem 1998; 71: 449–458.

    Article  PubMed  CAS  Google Scholar 

  21. Lazowski DA, Fraher LJ, Hodsman A, Steer B, Mdodrowski D, Han VKM. Regional variation of insulin-like growth factor-I gene expression in mature rat bone and cartilage. Bone 1994; 15: 563–576.

    Article  PubMed  CAS  Google Scholar 

  22. Middleton J, Arnott N, Beresford J. Osteoblasts and osteoclasts in adult human osteophyte tissue express the mRNAs for insulin-like growth factors I and II and the type I IGF receptor. Bone 1995; 16: 287–293.

    Article  PubMed  CAS  Google Scholar 

  23. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. [Review]. Endocr Rev 1995; 16: 3–34.

    PubMed  CAS  Google Scholar 

  24. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev 1995; 16: 143–163.

    PubMed  CAS  Google Scholar 

  25. Slootweg MC, Hoogerbrugge CM, de Poorter TL, Duursma SA, Van Buul-Offers SC. The presence of classical insulin-like growth factor (IGF) type-I and type-II receptors on mouse osteoblasts: autocrine/ paracrine growth effects of IGFs. J Endocrinol 1990; 125: 271–277.

    Article  PubMed  CAS  Google Scholar 

  26. Mohan S, Baylink DJ. Characterization of the IGF regulatory system in bone. [Review]. Adv Exp Med Biol 1993; 343: 397–406.

    Article  PubMed  CAS  Google Scholar 

  27. Centrella M, McCarthy TL, Canalis E. Receptors for insulin-like growth factors-I and -II in osteoblastenriched cultures from fetal rat bone. Endocrinology 1990; 126, 39–44.

    CAS  Google Scholar 

  28. Mohan S, Baylink DJ. The role of insulin-like growth factor-II in the coupling of bone formation to resorption. In: Spencer EM, ed. Modern Concepts of Insulin-Like Growth Factors. Elsevier, New York, 1991, pp. 169–184.

    Google Scholar 

  29. Raile K, Kessler HU, Pfuender M, Blum WF, Kolb H, Schwarz HP, Kiess W. Human osteosarcoma (U-2 OS) cells express both insulin-like growth factor-I (IGF-I) receptors and insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptors and synthesize IGF-II: autocrine growth stimulation by IGF-II via IGF-I receptor. J Cell Physiol 1994; 159: 531–541.

    Article  PubMed  CAS  Google Scholar 

  30. Nakao Y, Takeda Y, Yamaguchi Y, Baylink DJ, Mohan S. Mitogenic and IGF binding protein binding activity of IGF-II analogs. J Bone Miner Res 1993; 8: S199 (Abstract).

    Google Scholar 

  31. Hou P, Sato T, Hofstetter W, Foged NT. Identification and characterization of the insulin-like growth factor I receptor in mature rabbit osteoclasts. J Bone Miner Res 1997; 12: 534–540.

    Article  PubMed  CAS  Google Scholar 

  32. Mochizuki H, Hakeda Y, Wakatsuki N, Usui N, Akashi S, Sato T, Tanaka K, Kumegawa M. Insulin-like growth factor-I supports formation and activation of osteoclasts. Endocrinology 1992; 131: 1075–1080.

    Article  PubMed  CAS  Google Scholar 

  33. Hill PA, Reynolds JJ, Meikle MC. Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. Endocrinology 1995; 136: 124–131.

    Article  PubMed  CAS  Google Scholar 

  34. Mohan S, Bautista CM, Wergedal J, Baylink DJ. Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action. Proc Natl Acad Sci USA 1989; 86: 8338–8342.

    Article  PubMed  CAS  Google Scholar 

  35. LaTour D, Mohan S, Linkhart TA, Baylink DJ, Strong DD. Inhibitory insulin-like growth factor-binding protein: cloning, complete sequence, and physiological regulation. Mol Endocrinol 1990; 4: 1806–1814.

    Article  PubMed  CAS  Google Scholar 

  36. Mohan S, Jennings JC, Linkhart TA, Baylink DJ. Isolation and purification of a low-molecular-weight skeletal growth factor from human bones. Biochim Biophys Acta 1986; 884: 234–242.

    Article  PubMed  CAS  Google Scholar 

  37. Bautista CM, Baylink DJ, Mohan S. Isolation of a novel insulin-like growth factor (IGF) binding protein from human bone: a potential candidate for fixing IGF-II in human bone. Biochem Biophys Res Commun 1991; 176: 756–763.

    Article  PubMed  CAS  Google Scholar 

  38. Conover CA. Insulin-like growth factor binding protein proteolysis in bone cell models. Prog Growth Factor Res 1995; 6: 301–309.

    Article  PubMed  CAS  Google Scholar 

  39. Hassager C, Fitzpatrick LA, Spencer EM, Riggs BL, Conover CA. Basal and regulated secretion of insulin-like growth factor binding proteins in rat osteoblast-like cell is cell specific. J Clin Endocrinol Metab 1992; 75: 228–233.

    Article  PubMed  CAS  Google Scholar 

  40. Mohan S. Insulin-like growth factor binding proteins in bone cell regulation. [Review]. Growth Regul 1993; 3: 67–70.

    PubMed  CAS  Google Scholar 

  41. McCarthy TL, Casinghino S, Centrella M, Canalis E. Complex pattern of insulin-like growth factor binding protein expression in primary rat osteoblast enriched cultures: regulation by prostaglandin E2, GH and the insulin-like growth factors. J Cell Physiol 1994; 160: 163–175.

    Article  PubMed  CAS  Google Scholar 

  42. Andress DL. A novel human insulin-like growth factor binding protein secreted by human osteoblastlike cells. Biochem Biophys Res Commun 1991; 176: 213–218.

    Article  PubMed  CAS  Google Scholar 

  43. Conover CA, Bale LK, Clarkson JT, Toning O. Regulation of insulin-like growth factor binding protein-5 messenger ribonucleic acid expression and protein availability in rat osteoblast-like cells. Endocrinology 1993; 132: 2525–2530.

    Article  PubMed  CAS  Google Scholar 

  44. Mohan S, Baylink DJ. Evidence that the inhibition of TE85 human bone cell proliferation by agents which stimulate cAMP production may in part be mediated by changes in the IGF-II regulatory system. Growth Regul 1991; 1: 110–118.

    PubMed  CAS  Google Scholar 

  45. Mohan S, Strong DD, Hilliker S, Malpe R, Lee K, Farley J, Baylink DJ. Dibutyryl cyclic adenosine monophosphate differentially regulates cell proliferation in low and high alkaline phosphatase SaOS2 human osteosarcoma cells: evidence for mediation by the insulin-like growth factor-II system. J Cell Physiol 1993; 156: 462–468.

    Article  PubMed  CAS  Google Scholar 

  46. Campbell PG, Wines K, Yanosick TB, Novak JF. Binding and activation of plasminogen on the surface of osteosarcoma cells. J Cell Physiol 1994; 159: 1–10.

    Article  PubMed  CAS  Google Scholar 

  47. Birnbaum RS, Wiren KM. Changes in insulin-like growth factor binding protein expression and secretion during the proliferation, differentiation and mineralization of primary cultures of rat osteoblasts. Endocrinology 1994; 135: 223–230.

    Article  PubMed  CAS  Google Scholar 

  48. Thrailkill KM, Siddhanti SR, Fowlkes JL, Quarles LD. Differentiation of MC3T3–E1 osteoblasts is associated with temporal changes in the expression of IGF-I and IGFBPs. Bone 1995; 17: 307–313.

    Article  PubMed  CAS  Google Scholar 

  49. Conover CA, Durham SK, Zapf J, Masiarz FR, Kiefer MC. Cleavage analysis of insulin-like growth factor (IGF)-dependent IGF-binding protein-4 proteolysis and expression of protease-resistant IGFbinding protein-4 mutants. J Biol Chem 1995; 270: 4395–4400.

    Article  PubMed  CAS  Google Scholar 

  50. Delany AM, Rydziel S, Canalis E. Autocrine down-regulation of collagenase-3 in rat bone cell cultures by insulin-like growth factors. Endocrinology 1996; 137: 4665–4670.

    Article  PubMed  CAS  Google Scholar 

  51. Kanzaki S, Hilliker S, Baylink DJ, Mohan S. Evidence that human bone cells in culture produce insulin-like growth factor-binding protein-4 and -5 proteases. Endocrinology 1994; 134: 383–392.

    Article  PubMed  CAS  Google Scholar 

  52. Mohan S, Strong DD, Linkhart TA, Baylink DJ. Regulation and actions of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in bone: physiological and clinical implications. In: Baxter RC, Gluckman PD, Rosenfeld RG, eds. The Insulin-Like Growth Factors and Their Regulatory Proteins. Excerpta Medica, Amsterdam, 1994, pp. 205–215.

    Google Scholar 

  53. Durham SK, Kiefer MC, Riggs BL, Conover CA. Regulation of insulin-like growth factor binding protein 4 by a specific insulin-like growth factor binding protein 4 proteinase in normal human osteoblast-like cells: implications in bone cell physiology. J Bone Miner Res 1994; 9: 111–117.

    Article  PubMed  CAS  Google Scholar 

  54. Durham SK, Riggs BL, Conover CA. The insulin-like growth factor-binding protein-4 (IGFBP-4)IGFBP-4 protease system in normal human osteoblast-like cells: regulation by transforming growth factor-beta. J Clin Endocrinol Metab 1994; 79: 1752–1758.

    Article  PubMed  CAS  Google Scholar 

  55. Durham SK, De Leon DD, Okazaki R, Riggs BL, Conover CA. Regulation of insulin-like growth factor (IGF)-binding protein-4 availability in normal human osteoblast-like cells: role of endogenous IGFs. J Clin Endocrinol Metab 1995; 80: 104–110.

    Article  PubMed  CAS  Google Scholar 

  56. Durham SK, Riggs BL, Harris SA, Conover CA. Alterations in insulin-like growth factor (IGF)dependent IGF-binding protein-4 proteolysis in transformed osteoblastic cells. Endocrinology 1995; 136: 1374–1380.

    Article  PubMed  CAS  Google Scholar 

  57. Qin X, Strong DD, Pham T, Baylink DJ, Mohan S. Studies on the mechanism by which insulin-like growth factor (IGF)-II enhances IGF binding protein (IGFBP)-4 proteolysis in human osteoblast cell conditioned medium. J Bone Miner Res 1997; 12: 51–60 (Abstract).

    Google Scholar 

  58. Conover CA, Kiefer MC. Regulation and biological effect of endogenous insulin-like growth factor binding protein-5 in human osteoblastic cells. J Clin Endocrinol Metab 1993; 76: 1153–1159.

    Article  PubMed  CAS  Google Scholar 

  59. Knutsen R, Honda Y, Strong DD, Sampath TK, Baylink DJ, Mohan S. Regulation of insulin-like growth factor system components by osteogenic protein-1 in human bone cells. Endocrinology 1995; 136: 857–865.

    Article  PubMed  CAS  Google Scholar 

  60. Thrailkill KM, Quarles LD, Nagase H, Suzuki K, Serra DM, Fowlkes JL. Characterization of insulin-like growth factor-binding protein 5-degrading proteases produced throughout murine osteoblast differentiation. Endocrinology 1995; 136: 3527–3533.

    Article  PubMed  CAS  Google Scholar 

  61. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C, Lang K, Baylink DJ. Studies on the mechanisms by which insulin-like growth factor (IGF) binding protein-4 (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. J Biol Chem 1995; 270: 20424–20431.

    Article  PubMed  CAS  Google Scholar 

  62. Campbell PG, Novak JF, Wines K, Walton PE. Localization of plasmin activity on osteosarcoma cells: cell surface proteolysis of insulin-like growth factor binding proteins. Growth Regul 1993; 3: 95–98.

    PubMed  CAS  Google Scholar 

  63. Lalou C, Silve C, Rosato R, Segovia B, Binoux M. Interactions between insulin-like growth factor-I (IGF-I) and the system of plasminogen activators and their inhibitors in the control of IGF-binding protein-3 production and proteolysis in human osteosarcoma cells. Endocrinology 1994; 135: 2318–2326.

    Article  PubMed  CAS  Google Scholar 

  64. Campbell PG, Novak JF. Insulin-like growth factor binding protein inhibits IGF action in human osteosarcoma cells. J Cell Physiol 1991; 149: 293–300.

    Article  PubMed  CAS  Google Scholar 

  65. Conover CA, DeLeon DD. Acid-activated insulin-like growth factor binding protein-3 proteolysis in normal and transformed cells. Role of cathepsin D. J Biol Chem 1994; 269: 7076–7080.

    PubMed  CAS  Google Scholar 

  66. Wergedal JE, Mohan S, Lundy M, Baylink DJ. Skeletal growth factor and other growth factors known to be present in bone matrix stimulate proliferation and protein synthesis in human bone cells. J Bone Miner Res 5: 179–186.

    Google Scholar 

  67. Linkhart TA, Jennings JC, Mohan S, Wakley GK, Baylink DJ. Characterization of mitogenic activities extracted from bovine bone matrix. Bone 1986; 7: 479–487.

    Article  PubMed  CAS  Google Scholar 

  68. Canalis E, Centrella M, Burch W, McCarthy TL. Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 1989; 83: 60–65.

    Article  PubMed  CAS  Google Scholar 

  69. Canalis E, Rydziel S, Delany AM, Varghese S, Jeffrey JJ. Insulin-like growth factors inhibit interstitial collagenase synthesis in bone cell cultures. Endocrinology 1995; 136: 1348–1354.

    Article  PubMed  CAS  Google Scholar 

  70. Strong DD, Beachler AL, Wergedal JE, Linkhart TA. Insulin-like growth factor-II and transforming growth factor beta regulate colllagen expression in osteoblast-like cells in vitro. J Bone Miner Res 1991; 6: 15–23.

    Article  PubMed  CAS  Google Scholar 

  71. Takeda Y, Baylink DJ, Linkhart TA, Edwall D, Kumegawa M, Mohan S. Calcitrophic hormones and growth factors regulate osteoclast survival in vitro. J Bone Miner Res 1994; 9: S311 (Abstract).

    Google Scholar 

  72. Rajaram S, Baylink DJ, Mohan S. Insulin-like growth factor binding proteins in serum and other body fluids: regulation and functions. Endocr Rev 1997; 18: 801–803.

    Article  PubMed  CAS  Google Scholar 

  73. Feyen JHM, Evans DB, Binkert C, Heinrich G, Geiss S, Kocher HP. Recombinant human (cys281) insulin-like growth factor binding protein 2 inhibits both basal and insulin-like growth factor-1 stimulated proliferation and collagen synthesis in fetal rat calvariae. J Biol Chem 1991; 266: 19469–19474.

    PubMed  CAS  Google Scholar 

  74. Ernst M, Rodan GA. Increased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of GH (GH): positive correlation with the presence of GH-induced IGF binding protein BP-3. Endocrinology 1990; 127: 807–814.

    Article  PubMed  CAS  Google Scholar 

  75. Amarnani S, Merriman HL, Linkhart TA, Baylink DJ, Mohan S. Autocrine regulators of MC3T3–E1 cell proliferation. J Bone Miner Res 1993; 8: 157–165.

    Article  PubMed  CAS  Google Scholar 

  76. Schiltz PM, Mohan S, Baylink DJ. Insulin-like growth factor binding protein-4 inhibits both basal and IGF-mediated chick pelvic cartilage growth in vitro. J Bone Miner Res 1993; 8: 391–396.

    Article  PubMed  CAS  Google Scholar 

  77. Andress DL, Birnbaum RS. Human osteoblast-derived insulin-like growth factor (IGF) binding protein-5 stimulates osteoblast mitogenesis and potentiates IGF action. J Biol Chem 1992; 267: 22467–22472.

    PubMed  CAS  Google Scholar 

  78. Andress DL, Loop SM, Zapf J, Kiefer MC. Carboxy-truncated insulin-like growth factor binding protein-5 stimulates mitogenesis in osteoblast-like cells. Biochem Biophys Res Commun 1993; 195: 25–30.

    Article  PubMed  CAS  Google Scholar 

  79. Kiefer MC, Schmid C, Waldvogel M, Schlapfer I, Futo E, Masiarz FR, Green K, Barr PJ, Zapf J. Recombinant human insulin-like growth factor binding proteins 4, 5, and 6: biological and physiochemical characterization. Growth Regul 1993; 3: 56–59.

    CAS  Google Scholar 

  80. Schmid C, Schalpfer I, Gostelipeter MA, Froesch ER, Zapf J. Effects and fate of human insulin-like growth factor binding protein-5 in rat osteoblast cultures. Am J Physiol 1996; 271: E1029–1035.

    PubMed  CAS  Google Scholar 

  81. Srinivasan N, Edwall D, Linkhart TA, Baylink DJ, Mohan S. Insulin-like growth factor binding protein-6 produced by human PC-3 prostate cancer cells: isolation, characterization and its biological action. J Endocrinol 1996; 149: 297–303.

    Article  PubMed  CAS  Google Scholar 

  82. Andress DL. Heparin modulates the binding of insulin-like growth factor (IGF) binding protein-5 to a membrane protein in osteoblastic cells. J Biol Chem 1995; 270: 28289–28296.

    PubMed  CAS  Google Scholar 

  83. Jones JI, Gockerman A, Busby WH Jr, Camacho-Hubner C, Clemmons DR. Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I. J Cell Biol 1993; 121: 679–687.

    Article  PubMed  CAS  Google Scholar 

  84. Oh Y, Muller HL, Lamson G, Rosenfeld RG. Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition. J Biol Chem 1993; 268: 14964–14971.

    PubMed  CAS  Google Scholar 

  85. Rajah R, Valentinis B, Cohen P. Insulin like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-bl on programmed cell death through a p53-and IGF-independent mechanism. J Biol Chem 1997; 272: 12181–12188.

    Article  PubMed  CAS  Google Scholar 

  86. Li WL, Fawcett J, Widmer HR, Fielder PJ, Rabkin R, Keller GA. Nuclear transport of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in opossum kidney cells. Endocrinology 1997; 138: 1763–1766.

    Article  PubMed  CAS  Google Scholar 

  87. Jaques G, Noll K, Wegmann B, Witten S, Kogan E, Radulescu RT, Havemann K Nuclear localization of insulin-like growth factor binding protein 3 in a lung cancer cell line. Endocrinology 1997; 138: 1767–1770.

    Article  PubMed  CAS  Google Scholar 

  88. Eriksen EF, Kassem M, Langdahl B. GH, insulin-like growth factors and bone remodelling. Eur J Clin Invest 1996; 26: 525–534.

    Article  PubMed  CAS  Google Scholar 

  89. Rosen CJ. GH, insulin-like growth factors, and the senescent skeleton: Ponce de Leon’s Fountain revisited? J Cell Biochem 1994; 56: 348–356.

    Article  PubMed  CAS  Google Scholar 

  90. Kalu DN, Liu CC, Slaerno E, Salih M, Ray M, Hollis BW. IGF-I partially prevents ovariectomyinduced bone loss: a comparative study with PTH. J Bone Miner Res 1991; 6: 548.

    Google Scholar 

  91. Ammann P, Rizzoli R, Meyer JM, Slosman D, Bonjour JP. IGF-I and palmidronate increase bone mineral density in ovariectomized adult rats. Am J Physiol 1993; 265: E770 - E776.

    PubMed  CAS  Google Scholar 

  92. Machwate M, Zerath E, Holy X, Pastoureau P, Marie PJ. Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 1994; 134: 1031–1038.

    Article  PubMed  CAS  Google Scholar 

  93. Bagi CM, DeLeon E, Brommage R, Adams S, Rosen D, Sommer A. Systemic administration of rhIGFI or rhIGF-UIGFBP-3 increases cortical bone and lean body mass in ovariectomized rats. Bone 1995; 16: 263S - 269S.

    Article  PubMed  CAS  Google Scholar 

  94. Bagi CM, Brommage R, Deleon L, Adams S, Rosen D, Sommer A. Benefit of systemically administered rhIGF-I andrhlGF-I/IGFBP-3 on cancellous bone in ovariectomized rats. J Bone Miner Res 1994; 9: 1301–1312.

    Article  PubMed  CAS  Google Scholar 

  95. Spencer EM, Liu CC, Si ECC, Howard GA. In vivo actions of insulin-like growth factor I on bone formation and resorption in rats. Bone 1991; 12: 21–26.

    Article  PubMed  CAS  Google Scholar 

  96. Zapf J, Froesch ER. Insulin-like growth factors/somatomedins: structure, secretion and biological actions and physiological role. Horm Res 1986; 24: 121–130.

    Article  PubMed  CAS  Google Scholar 

  97. Verhaeghe J, van Bree R, van Herck E, Thomas H, Skottner A, Dequeker J, Mosekilde LI, Einhorn TA, Bouillon R. Effects of recombinant human GH and insulin-like growth factor-I, with or without 17f3estradiol, on bone and mineral homeostasis of aged ovariectomized rats. J Bone Miner Res 1996; 11: 1723–1735.

    Article  PubMed  CAS  Google Scholar 

  98. Baker J, Liu J, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal development. Cell 1993; 75: 73–82.

    PubMed  CAS  Google Scholar 

  99. Liu J, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (IGF-I) and type 1 IGF receptor (IGF1r). Cell 1993; 75: 59–72.

    PubMed  CAS  Google Scholar 

  100. Johansson AG, Lindh E, Ljunghall S. IGF-I stimulates bone turnover in osteoporosis. Lancet 1992; 339: 16–19.

    Article  Google Scholar 

  101. Ebeling PR, Jones JD, O’Fallon WM, Janes CH, Riggs BL. Short-term effects of recombinant human IGF-I on bone turnover in normal women. J Clin Endocrinol Metab 1993; 77: 1384–1387.

    Article  PubMed  CAS  Google Scholar 

  102. Grinspoon S, Baum H, Peterson S, Klibanski A. Effects of rhIGF-I administration on bone turnover during short-term fasting. J Clin Invest 1995; 96: 900–906.

    Article  PubMed  CAS  Google Scholar 

  103. Johansson G, Lindh E, Kollerup G, Ljunghall S. Dose-dependent effects of IGF-I on metabolism of collagen type I in male osteoporosis. J Bone Miner Res 1995; 10: S393.

    Google Scholar 

  104. Johansson AG, Lindh E, Blum WF, Kollerup G, Sorenson OH, Ljunghall S. Effects of GH and IGFI in men with idiopathic osteoporosis. J Clin Endocrinol Metab 1996; 81: 44–48.

    Article  PubMed  CAS  Google Scholar 

  105. Ghiron LJ, Thompson JL, Holloway L, Hintz RL, Butterfield GE, Hoffman AR, Marcus R. Effects of recombinant insulin-like growth factor-I and GH on bone turnover in elderly women. J Bone Miner Res 1995; 10: 1844–1852.

    Article  PubMed  CAS  Google Scholar 

  106. Bagi CM, Brommage R, Deleon L, Adams S, Rosen D, Sommer A. Benefit of systemically administered rhIGF-I and rhIGF-I/IGFBP-3 on cancellous bone in ovariectomized rats. J Bone Miner Res 1994; 9: 1301–1312.

    Article  PubMed  CAS  Google Scholar 

  107. Bagi CM, DeLeon E, Brommage R, Rosen D, Sommer A. Treatment of ovariectomized rats with the complex of rhIGF-I/IGFBP-3 increases cortical and cancellous bone mass and improves structure in the femoral neck. Calcif Tissue Int 1995; 57: 40–46.

    Article  PubMed  CAS  Google Scholar 

  108. Kling L, Dony C, Leser U, Popp F, Bauss F, Lang K. Insulin-like growth factor binding protein-5 increases the osteoanabolic effects of insulin-like growth factor-I on calvarial bone in mice after local administration. J Bone Miner Res 1996; 11: S153 (Abstract).

    Google Scholar 

  109. McCarthy TL, Centrella M, Canalis E. Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone. Endocrinology 1989; 124: 1247–1253.

    CAS  Google Scholar 

  110. Linkhart TA, Mohan S. Parathyroid hormone stimulates release of insulin-like growth factor-I (IGFI) and IGF-II from neonatal mouse calvaria in organ culture. Endocrinology 1989; 125: 1484–1491.

    Article  PubMed  CAS  Google Scholar 

  111. McCarthy TL, Ji CH, Shu H, Casinghino S, Crothers K, Rotwein P, Centrella M. 1713-Estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures. J Biol Chem 1997; 272: 18132–18139.

    Article  PubMed  CAS  Google Scholar 

  112. Ernst M, Rodan GA. Estradiol regulation of insulin-like growth factor-I expression in osteoblastic cells: evidence for transcriptional control. Mol Endocrinol 1991; 5: 1081–1089.

    Article  PubMed  CAS  Google Scholar 

  113. Gray TK, Mohan S, Linkhart TA, Baylink DJ. Estradiol stimulates in vitro the secretion of insulin-like growth factors by the clonal osteoblastic cell line, UMR106. Biochem Biophys Res Commun 1989; 158: 407–412.

    Article  PubMed  CAS  Google Scholar 

  114. McCarthy TL, Centrella M, Canalis E. Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures. J Biol Chem 1990; 265: 15353–15356.

    PubMed  CAS  Google Scholar 

  115. Thomas MJ, Umayahara Y, Shu H, Centrella M, Rotwein P, McCarthy TL. Identification of the cAMP response element that controls transcriptional activation of the insulin-like growth factor-I gene by prostaglandin E2 in osteoblasts. J Biol Chem 1996; 271: 21835–21841.

    Article  PubMed  CAS  Google Scholar 

  116. Ishizuka T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S, Yamaguchi A. Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest 1997; 99: 2961–2970.

    Article  Google Scholar 

  117. Finkelman RD, Mohan S, Linkhart TA, Abraham SM, Boussy JP, Baylink DJ. PTH stimulates the proliferation of TE-85 human osteosarcoma cells by a mechanism not involving either increased cAMP or increased secretion of IGF-I, IGF-II or TGF beta. Bone Miner 1992; 16: 89–100.

    Article  PubMed  CAS  Google Scholar 

  118. Chen TL, Chang LY, Bates RL, Perlman AJ. Dexamethasone and 1,25-dihydroxyvitamin D3 modulation of insulin-like growth factor binding proteins in rat osteoblast-like cell cultures. Endocrinology 1991; 128: 73–80.

    Article  PubMed  CAS  Google Scholar 

  119. Canalis E. Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 1996; 81: 3441–3447.

    Article  PubMed  CAS  Google Scholar 

  120. Scharla SH, Strong DD, Mohan S, Baylink DJ, Linkhart TA. I,25-Dihydroxyvitamin D3 differentially regulates the production of insulin-like growth factor I (IGF-I) and IGF-binding protein-4 in mouse osteoblasts. Endocrinology 1991; 129: 3139–3146.

    Article  PubMed  CAS  Google Scholar 

  121. Linkhart TA, MacCharles DC. Interleukin-1 stimulates release of insulin-like growth factor-I from neonatal mouse calavaria by a prostaglandin synthesis-dependent mechanism. Endocrinology 1992; 131: 2297–2305.

    Article  PubMed  CAS  Google Scholar 

  122. Gabbitis B, Pash J, Canalis E. Regulation of insulin-like growth factor-II synthesis in bone cell cultures by skeletal growth factors. Endocrinology 1994; 135: 284–289.

    Article  Google Scholar 

  123. Tremollieres FA, Strong DD, Baylink DJ, Mohan S. Insulin-like growth factor II and transforming growth factor beta 1 regulate insulin-like growth factor I secretion in mouse bone cells. Acta Endocrinol 1991; 125: 538–546.

    PubMed  CAS  Google Scholar 

  124. Diez JJ, Iglesias P, Sastre J, Mendez J, Selgas R, Gómez-Pan A. GH responses to GH-releasing hormone and clonidine before and after erythropoietin therapy in CAPD patients. Nephron 1996; 74: 548–554.

    Article  PubMed  CAS  Google Scholar 

  125. Okazaki R, Durham SK, Riggs BL, Conover CA. Transforming growth factor-beta and forskolin increase all classes of insulin-like growth factor-I transcripts in normal human osteoblast-like cells. Biochem Biophys Res Commun 1995; 207: 963–970.

    Article  PubMed  CAS  Google Scholar 

  126. Strom P, Ljunghall S, Melhus H. Adult human osteoblast-like cells do not express insulin-like growth factor-I. Biochem Biophys Res Commun 1994; 199: 78–82.

    Article  PubMed  CAS  Google Scholar 

  127. Tremollieres FA, Strong DD, Baylink DJ, Mohan S. Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production. Acta Endocrinol 1992; 126: 329–337.

    PubMed  CAS  Google Scholar 

  128. Mohan S, Chevalley T, Linkhart TA, Douglas D, Libanati C, Baylink DJ. Reduction in IGF-I and IGFII production may mediate glucocorticoid inhibition of human bone cell proliferation. J Bone Miner Res 1995; 10: S492(Abstract).

    Google Scholar 

  129. McCarthy TL, Centrella M, Canalis E. Cortisol inhibits the synthesis of insulin-like growth factor-I in skeletal cells. Endocrinology 1990; 126: 1569–1575.

    CAS  Google Scholar 

  130. Yeh LC, Adamo ML, Kitten AM, Olson MS, Lee JC. Osteogenic protein-l-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells. Endocrinology 1996; 137: 1921–1931.

    Article  PubMed  CAS  Google Scholar 

  131. Canalis E, Pash J, Gabbitas B, Rydziel S, Varghese S. Growth factors regulate the synthesis of insulin-like growth factor-I in bone cell cultures. Endocrinology 1993; 133: 33–38.

    Article  PubMed  CAS  Google Scholar 

  132. Zaman G, Suswillo RFL, Cheng ZM, Tavares LA, Lanyon LE. Early responses to dynamic strain change and prostaglandins in bone derived cells in culture. J Bone Miner Res 1997; 12: 769–777.

    Article  PubMed  CAS  Google Scholar 

  133. Rawlinson SC, Mohan S, Baylink DJ, Lanyon LE. Exogenous prostacyclin, but not prostaglandin E2, produces similar responses in both G6PD activity and RNA production as mechanical loading, and increases IGF-II release, in adult cancellous bone in culture. Calcif Tissue Int 1993; 53: 324–329.

    Article  PubMed  CAS  Google Scholar 

  134. Fitzsimmons RJ, Strong DD, Mohan S, Baylink DJ. Low-amplitude, low-frequency electric field-stimulated bone cell proliferation may in part be mediated by increased IGF-II release. J Cell Physiol 1992; 150: 84–89.

    Article  PubMed  CAS  Google Scholar 

  135. Fitzsimmons RJ, Ryaby JT, Mohan S, Magee FP, Baylink DJ. Combined magnetic fields increase insulin-like growth factor-II in TE-85 human osteosarcoma bone cell cultures. Endocrinology 1995; 136: 3100–3106.

    Article  PubMed  CAS  Google Scholar 

  136. Honda Y, Landale EC, Strong DD, B aylink DJ, Mohan S. Recombinant synthesis of insulin-like growth factor-binding protein-4 (IGFBP-4): development, validation, and application of a radioimmunoassay for IGFBP-4 in human serum and other biological fluids. J Clin Endocrinol Metab 1996; 81: 1389–1396.

    Article  PubMed  CAS  Google Scholar 

  137. Mohan S, Srinivasan N, Pham T, Linkhart TA, Baylink DJ. Opposing effects of TGF beta1 on IGF binding protein (IGFBP)-4 and IGFBP-5 level in the conditioned medium of normal human osteoblasts: evidence for mediation via different post receptor signaling mechanism. In: 79th Annual Meeting of the Endocrine Society, Minneapolis, MN, June 11–14,1997 (Abstract).

    Google Scholar 

  138. Qin X, Morales S, Mohan S, Linkhart TA, Baylink DJ, Strong DD. Structural and functional analysis of IGF binding protein-4 promoter: demonstration of functional cAMP response elements. J Bone Miner Res 1996; 11: S309(Abstract).

    Google Scholar 

  139. Pash JM, Canalis E. Transcriptional regulation of insulin-like growth factor-binding protein-5 by prostaglandin E2 in osteoblast cells. Endocrinology 1996; 137: 2375–2382.

    Article  PubMed  CAS  Google Scholar 

  140. Scharla SH, Strong DD, Mohan S, Chevalley T, Linkhart TA. Effect of tumor necrosis factor-alpha on the expression of insulin-like growth factor I and insulin-like growth factor binding protein 4 in mouse osteoblasts. Eur J Endocrinol 1994; 131: 293–301.

    Article  PubMed  CAS  Google Scholar 

  141. Scharla SH, Strong DD, Rosen C, Mohan S, Holick M, Baylink DJ, Linkhart TA. 1,25-Dihydroxyvitamin D3 increases secretion of insulin-like growth factor binding protein-4 (IGFBP-4) by human osteoblast-like cells in vitro and elevates IGFBP-4 serum levels in vivo. J Clin Endocrinol Metab 1993; 77: 1190–1197.

    Article  PubMed  CAS  Google Scholar 

  142. Kassem M, Okazaki R, DeLeon DD, Harris SA, Robinson JA, Spelsberg TC, Conover CA, Riggs BL. Potential mechanism of estrogen mediated decrease in bone formation: estrogen increases production of inhibitory insulin-like growth factor binding protein-4 in human osteoblastic cell line with high levels of estrogen receptors. Proc Assoc Am Physicians 1996; 108: 154–164.

    Google Scholar 

  143. Okazaki R, Riggs BL, Conover CA. Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells. Endocrinology 1994; 134: 126–132.

    Article  PubMed  CAS  Google Scholar 

  144. Gabbitas B, Canalis E. Cortisol enhances the transcription of insulin-like growth factor-binding protein-6 in cultured osteoblasts. Endocrinology 1996; 137: 1687–1692.

    Article  PubMed  CAS  Google Scholar 

  145. Chevalley T, Strong DD, Mohan S, Baylink DJ, Linkhart TA. Evidence for a role for insulin-like growth factor binding proteins in glucocorticoid inhibition of normal human osteoblast-like cell proliferation. Eur J Endocrinol 1996; 134: 591–601.

    Article  PubMed  CAS  Google Scholar 

  146. Gabbitas B, Canalis E. Retinoic acid stimulates the transcription of insulin-like growth factor binding protein-6 in skeletal cells. J Cell Physiol 1996; 169: 15–22.

    Article  PubMed  CAS  Google Scholar 

  147. Zhou YH, Mohan S, Linkhart TA, Baylink DJ, Strong DD. Retinoic acid regulates insulin-like growth factor-binding protein expression in human osteoblast cells. Endocrinology 1996; 137: 975–983.

    Article  PubMed  CAS  Google Scholar 

  148. Boonyaratankornkit V, Strong DD, Mohan S, Baylink DJ, Beck C, Linkhart TA. A CACCC box motif in the IGF binding protein-5 promoter mediates progesterone transactivation of IGFBP-5 transcription in human osteoblasts. J Bone Miner Res 1996; 11:S131(Abstract).

    Google Scholar 

  149. Hayden JM, Strong DD, Baylink DJ, Powell DR, Sampath TK, Mohan S. Osteogenic protein-1 stimulates production of insulin-like growth factor binding protein-3 nuclear transcripts in human osteosarcoma cells. Endocrinology 1997; 138: 4240–4247.

    Article  PubMed  CAS  Google Scholar 

  150. Bailey D, Mohan S, Linkhart T. IL-1 alpha increases IGF binding protein-4 production in normal human bone cells via a prostaglandin dependent mechanism. J Bone Miner Res 1996; 11: S309 (Abstract).

    Google Scholar 

  151. Mohan S, Strong DD, Lempert UG, Tremollieres F, Wergedal JE, Baylink DJ. Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells. Acta Endocrinologica 1992; 127: 555–564.

    PubMed  CAS  Google Scholar 

  152. Dong Y, Canalis E. Insulin-like growth factor (IGF) I and retinoic acid induce the synthesis of IGF-binding protein 5 in rat osteoblastic cells. Endocrinology 1995; 136: 2000–2006.

    Article  PubMed  CAS  Google Scholar 

  153. Conover CA, Clarkson JT, Bale LK. Phorbol ester tumor promoters regulate insulin-like growth factor-binding protein-4 proteolysis. Endocrinology 1993; 133: 1347–1351.

    Article  PubMed  CAS  Google Scholar 

  154. Rosen CJ, Donahue LR. Insulin-like growth factors: potential therapeutic options for osteoporosis. Trends Endocrinol Metab 1995; 6: 235–240.

    Article  PubMed  CAS  Google Scholar 

  155. Mohan S, Baylink DJ. Development of a simple valid method for the complete removal of insulin-like growth factor (IGF)-binding proteins from IGFs in human serum and other biological fluids: comparison with acid-ethanol treatment and C18 Sep-Pak separation. J Clin Endocrinol Metab 1995; 80: 637–647.

    Article  PubMed  CAS  Google Scholar 

  156. Romagnoli E, Minisola S, Carnevale V, Rosso R, Pacitti MT, Scarda A, Scarnecchia L, Mazzuoli G. Circulating levels of insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor I (IGF-I) in perimenopausal women. Osteopor Int 1994; 4: 305–308.

    Article  CAS  Google Scholar 

  157. Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K. Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 1997; 12: 1272–1279.

    Article  PubMed  CAS  Google Scholar 

  158. Nasu M, Sugimoto T, Chihara M, Hiraumi M, Kurimoto F, Chihara K. Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. Eur J Endocrinol 1997; 136: 608–616.

    Article  PubMed  CAS  Google Scholar 

  159. Reed B, Zerwekh JE, Sakhaee K, Breslau NA, Gottschalk F, Pak CYC. Serum IGF-I is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res 1995; 10: 1218–1224.

    Article  PubMed  CAS  Google Scholar 

  160. Johannsson G, Eriksen EF, Lindh E, Langdahl B, Blum WF, Lindahl A, Ljunggren O, Ljunghall S. Reduced serum levels of the GH-dependent insulin-like growth factor binding protein and a negative bone balance at the level of individual remodeling units in idiopathic osteoporosis in men. J Clin Endocrinol Metab 1997; 82: 2795–2798.

    Article  Google Scholar 

  161. Mohan S, Baylink DJ. Editorial: Insulin-like growth (IGF)-binding proteins in serum: do they have additional roles besides modulating the endocrine IGF actions? J Clin Endocrinol Metab 1996; 81: 3817–3820.

    Article  PubMed  CAS  Google Scholar 

  162. Mohan S, Farley JR, Baylink DJ. Age-related changes in IGFBP-4 and IGFBP-5 levels in human serum and bone: implications for bone loss with aging. Prog Growth Factor Res 1995; 6: 465–473.

    Article  PubMed  CAS  Google Scholar 

  163. Mohan S, Libanati C, Dony C, Lang K, Srinivasan N, Baylink DJ. Development, validation, and application of a radioimmunoassay for insulin-like growth factor binding protein-5 in human serum and other biological fluids. J Clin Endocrinol Metab 1995; 80: 2638–2645.

    Article  PubMed  CAS  Google Scholar 

  164. Nicolas V, Mohan S, Honda Y, Prewett A, Finkelman RD, Baylink DJ, Farley JR. An age-related decrease in the concentration of insulin-like growth factor binding protein-5 in human cortical bone. Calcif Tissue Int 1995; 57: 206–212.

    Article  PubMed  CAS  Google Scholar 

  165. Nicolas V, Prewett A, Bettica P, Mohan S, Finkelman RD, Baylink DJ, Farley JR. Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging. J Clin Endocrinol Metab 1994; 78: 1011–1016.

    Article  PubMed  CAS  Google Scholar 

  166. Boonen S, Mohan S, Dequeker J, Aerssens J, Bouillon R, Baylink DJ. Deficit of the serum stimulatory components of insulin-like growth factor system in patients with osteoporosis and femoral neck fracture. J Bone Miner Res 1996; II: S328(Abstract).

    Google Scholar 

  167. Boonen S, Mohan S, Dequeker J, Aerssens J, Bouillon R, Baylink DJ. Prospective study of the serum insulin-like growth factor system components (IGFs) in patients with senile osteoporosis and trochanteric fracture compared with age-matched controls. J Bone Miner Res 1997; 12: S122 (Abstract).

    Article  Google Scholar 

  168. Boonen S, Lesaffre E, Aerssens J, Pelemans W, Dequeker J, Bouillon R. Deficiency of the GH-insulinlike growth factor-I axis potentially involved in age-related alterations in body composition. Gerontology 1996; 42: 330–338.

    Article  PubMed  CAS  Google Scholar 

  169. Pfeilschifter J. GH and bone metabolism: the role of the vitamin D system. Eur J Endocrinol 136: 30–32.

    Google Scholar 

  170. Ono T, Kanzaki S, Seino Y, Baylink DJ, Mohan S. Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF binding protein-3 and -5, and bone alkaline phosphatase isoenzyme. J Clin Endocrinol Metab 1996; 81: 2111–2116.

    Article  PubMed  CAS  Google Scholar 

  171. Rosen CJ, Donahue LR, Hunter SJ. Insulin-like growth factors and bone: the osteoporosis connection. Proc Soc Exp Biol Med 1994; 206: 83–102.

    Article  PubMed  CAS  Google Scholar 

  172. Bagi C, van der Meulen M, Brommage R, Rosen D, Sommer A. The effect of systemically administered rhIGF-I/IGFBP-3 complex on cortical bone strength and structure in ovariectomized rats. Bone 1995; 16: 559–565.

    Article  PubMed  CAS  Google Scholar 

  173. Rosen CJ, Dimai HP, Vereault D, Donahue LR, Beamer WG, Farley J, Linkhart S, Linkhart T, Mohan S, Baylink DJ. Circulating and skeletal insulin-like growth factor-I (IGF-I) concentrations in two inbred strains of mice with different bone mineral densities. Bone 1997; 21: 217–223.

    Article  PubMed  CAS  Google Scholar 

  174. Libanati C, Rajaram S, Baylink DJ, Mohan S. In a longitudinal prospective study, glucocorticoid (GC) therapy causes a marked reduction in bone formation markers and stimulatory insulin-like growth factor (IGF) system components. J Bone Miner Res 1996; 11: S150(Abstract).

    Google Scholar 

  175. Mohan S, Baylink DJ. Insulin-like growth factor system components and the coupling of bone formation to resorption. Horm Res 1996; 45: 59–62.

    Article  PubMed  CAS  Google Scholar 

  176. Farley JR, Tarbaux N, Murphy LA, Masuda T, Baylink DJ. In vitro evidence that bone formation may be coupled to resorption by release of mitogen(s) from resorbing bone. Metab Clin Exp 1987; 36: 314–321.

    Article  PubMed  CAS  Google Scholar 

  177. Hayden JM, Mohan S, Baylink DJ. The insulin-like growth factor system and the coupling of formation to resorption. [Review]. Bone 1995; 17: 93S - 98S.

    Article  PubMed  CAS  Google Scholar 

  178. Finkelman RD, Linkhart TA, Mohan S, Lau KH, Baylink DJ, Bell NH. Vitamin D deficiency causes a selective reduction in deposition of transforming growth factor beta in rat bone: possible mechanism for impaired osteoinduction. Proc Natl Acad Sci USA 1991; 88: 3657–3660.

    Article  PubMed  CAS  Google Scholar 

  179. Dequeker J, Mohan S, Finkelman RD, Aerssens J, Baylink DJ. Generalized osteoarthritis associated with increased insulin-like growth factor types I and II and transforming growth factor beta in cortical bone from the iliac crest. Possible mechanism of increased bone density and protection against osteoporosis. Arthritis Rheum 1993; 36: 1702–1708.

    Article  PubMed  CAS  Google Scholar 

  180. Cappon J, Brasel JA, Mohan S, Cooper DM. Effect of brief exercise on circulating insulin-like growth factor I. J Appl Physiol 1994; 76: 2490–2496.

    Article  PubMed  CAS  Google Scholar 

  181. Schwartz AJ, Brasel JA, Hintz RL, Mohan S, Cooper DM. Acute effects of brief low-and high-intensity exercise on circulating IGF-I, IGF-II, and IGF binding protein-3 and the proteolysis in young healthy men. J Clin Endocrinol Metab 1996; 81: 3492–3497.

    Article  Google Scholar 

  182. Ghiron LJ, Thompson JL, Holloway L, Hintz RL, Butterfield GE, Hoffman AR, Marcus R. Effects of recombinant insulin-like growth factor-I and GH on bone turnover in elderly women. J Bone Miner Res 1995; 10: 1844–1852.

    Article  PubMed  CAS  Google Scholar 

  183. Mauras N, Doi SQ, Shapiro JR. Recombinant human insulin-like growth factor I, recombinant human GH, and sex steroids: effects on markers of bone turnover in humans. J Clin Endocrinol Metab 1996; 81: 2222–2226.

    Article  PubMed  CAS  Google Scholar 

  184. Johans son AG, Forslund A, Hambraeus L, Blum WF, Ljunghall S. GH-dependent insulin-like growth factor binding protein is a major determinant of bone mineral density in healthy men. J Bone Miner Res 1994; 9: 915–921.

    Article  PubMed  CAS  Google Scholar 

  185. Hintz RL. Current and potential therapeutic uses of GH and insulin-like growth factor I. Endocrinol Metab Clin North Am 1996; 25: 759–773.

    Article  PubMed  CAS  Google Scholar 

  186. Honda Y, Fitzsimmons RJ, Baylink DJ, Mohan S. Effects of extracellular calcium on insulin-like growth factor II in human bone cells. J Bone Miner Res 1995; 10: 1660–1665.

    Article  PubMed  CAS  Google Scholar 

  187. Rosen C, Donahue LR, Hunter S, Holick M, Kavookjian H, Kirschenbaum A, Mohan S, Baylink DJ. The 24/25-kDa serum insulin-like growth factor-binding protein is increased in elderly women with hip and spine fractures. J Clin Endocrinol Metab 1992; 74: 24–27.

    Article  PubMed  CAS  Google Scholar 

  188. Pfeilschifter J, Diel I, Pilz U, Brunotte K, Naumann A, Ziegler R. Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decrease with age. J Bone Miner Res 1993; 8: 707–717.

    Article  PubMed  CAS  Google Scholar 

  189. D’ Avis PY, Frazier CR, Shapiro JR, Fedarko NS. Age-related changes in effects of insulin-like growth factor I on human osteoblast-like cells. Biochem J 1997; 324: 753–760.

    Google Scholar 

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Mohan, S., Baylink, D.J. (1999). IGF System Components and Their Role in Bone Metabolism. In: Rosenfeld, R.G., Roberts, C.T. (eds) The IGF System. Contemporary Endocrinology, vol 17. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-712-3_20

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