Insulin-Like Growth Factors and Skeletal Remodeling

  • Julie Patterson
  • Jay R. Shapiro
  • Marc R. Blackman
Conference paper
Part of the Serono Symposia USA book series (SERONOSYMP)

Abstract

Research during the past several years has afforded considerable insight into the integrated system of hormones, cytokines, and locally acting growth factors that regulate the differentiation of bone cell precursors and modulate bone cell activity. Insulin-like growth factor I (IGF-I) is a peptide synthesized by the osteoblast that plays a key role in skeletal extracellular matrix synthesis (1). IGF-II, also synthesized by the osteoblast, has similar effects on osteoblast differentiation, but is less potent as regards protein synthesis (2). The osteoblast, via its synthesis of various other growth factors and cytokines, subserves autocrine and paracrine functions that coordinate and mediate the metabolic activities of bone marrow stromal cells, cells of the monocyte-macrophage series, bone lining cells, and osteoclasts (3). This chapter discusses the synthesis of IGFs by bone cells and the metabolic actions of IGF-I on osteoblasts and their precursors and presents recent data describing the effect of recombinant human IGF-I (rhIGF-I) on skeletal turnover in postmenopausal women.

Keywords

Estrogen Osteoporosis Polypeptide Prostaglandin Glucocorticoid 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Canalis E. Effect of insulin-like growth factor I on DNA and protein synthesis in cultured rat calvariae. J Clin Invest 1980;66:709–19.PubMedCrossRefGoogle Scholar
  2. 2.
    Fournier B, Ferralli JM, Price PA, Schaeppi JM. Comparison of the effects of insulin-like growth factors I and II on the human osteosarcoma cell line, OHS-4. J Endocrinol 1993;136:173–80.PubMedCrossRefGoogle Scholar
  3. 3.
    Bab IA, Einhorn TA. Regulatory role of osteogenic growth polypeptides in bone formation and hematopoiesis. Crit Rev Eukaryot Gene Exp 1993; 3:31–46.Google Scholar
  4. 4.
    Canalis E, Pash J, Varghese S. Skeletal growth factors. Crit Rev Eukaryot Gene Exp 1993;3:155–66.Google Scholar
  5. 5.
    Langdahl BL, Kassem M, Hougaaard D, et al. Insulin-like growth factor II (IGF-II) is the predominant IGF expressed by normal human osteoblasts. J Bone Miner Res 1993;8:s366.Google Scholar
  6. 6.
    Chen TL, Liu F, Bates RL, Hintz RL. Further characterization of insulin-like growth factor binding proteins in rat osteoblast-like cell cultures: modulation by 17f3-estradiol and human growth hormone. Endocrinology 1991;128: 2489–96.PubMedCrossRefGoogle Scholar
  7. 7.
    Yateman ME, Claggey DC, Cwyfan Hughes SC, Frost VJ, Wass JAH, Holly JM. Cytokines modulate the sensitivity of human fibroblasts to stimulation with insulin-like growth factor-I (IGF-I) by altering endogenous IGF-binding protein production. J Endocrinol 1993;137:151–9.PubMedCrossRefGoogle Scholar
  8. 8.
    McCarthy TL, Centrella M, Canalis E. Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblastenriched cultures from fetal rat bone. Endocrinology 1989;124:1247–53.PubMedCrossRefGoogle Scholar
  9. 9.
    McCarthy TL, Centrella M, Canalis E. Cyclic AMP induces insulin-like growth factor I synthesis in osteoblast-enriched cultures. J Biol Chem 1990; 265:15353–6.PubMedGoogle Scholar
  10. 10.
    Ernst M, Heath JK, Rodan G. Estradiol effects on proliferation, messenger ribonucleic acid for collagen and insulin-like growth factor-I and parathyroid hormone stimulated adenylate cyclase activity in osteoblastic cells from calvariae and long bones. Endocrinology 1989;125:825–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Murphy LJ, Friesen HG. Differential effects of estrogen and growth hormone on uterine and hepatic insulin-like growth factor I gene expression in the ovariectomized hypophysectomized rat. Endocrinology 1988;122:325.PubMedCrossRefGoogle Scholar
  12. 12.
    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 Comm 1989;158:407–12.PubMedCrossRefGoogle Scholar
  13. 13.
    Canalis E, Pash J, Gabbitas B, Rydzeil S, Varghese S. Growth factors regulate the synthesis of insulin-like growth factor-I in bone cell cultures. Endocrinology 1993;133:33–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Kream BE, Petersen DN, Raisz LG. Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae. Bone 1990;11:411–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Hock JM, Centrella M, Canalis E. Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. Endocrinology 1988;122:254–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Pfeilschifter J, Oechsner M, Naumann A, Gronwald R, Minne HW, Ziegler R. Stimulation of bone matrix apposition in vitro by local growth factors: a comparison between insulin-like growth factor I, platelet-derived growth factor and transforming growth factor-ß. Endocrinology 1990;127:69–75.PubMedCrossRefGoogle Scholar
  17. 17.
    Tanaka H, Quarto R, Williams S, Barnes J, Liang CT. In vivo and in vitro effects of IGF-I on femoral gene expression in aged rats [Abstract]. J Bone Miner Res 1993;8:156.Google Scholar
  18. 18.
    Canalis E, Rydziel S, Gabbitas B, Varghese S. Insulin-like growth factors decrease collagen degradation and collagenase expression in bone cultures [Abstract]. J Bone Miner Res 1993:481.Google Scholar
  19. 19.
    Thrailkill K, Quarles LD. Osteoblast differentiation is associated with temporal differences in expression of insulin-like growth factor-I and IGF binding proteins. J Bone Miner Res 1993;8:s311.Google Scholar
  20. 20.
    Blum WF, Reoin JF, Kietzmann K, Ranke MB, Bierich JR. Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I. Endocrinology 1989;125:766–72.PubMedCrossRefGoogle Scholar
  21. 21.
    McCarthy TL, Wozney J, Centrella M. Cell population selective control of insulin-like growth factor (IGF-I) and IGF-II binding by bone morphogenetic protein (BMP-2) in fetal rat bone cell cultures [Abstract]. J Bone Miner Res 1993:710.Google Scholar
  22. 22.
    Scharla SH, Strong DD, Rosen C, et al. 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;77:1190–5.PubMedCrossRefGoogle Scholar
  23. 23.
    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;267:22467–72.PubMedGoogle Scholar
  24. 24.
    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;121:679–87.PubMedCrossRefGoogle Scholar
  25. 25.
    Schmid C, Schlapfer I, Foresch ER, Kiefer M, Zapf J. Insulin-like growth factor binding protein-5 is a mitogen regulated by insulin-like growth factor-I, parathyroid hormone and 1,25 dihydroxyvitamin D3 in vitro. J Bone Miner Res 1993;8(suppl 1):s293.Google Scholar
  26. 26.
    Okazaki R, Spelberg TC, Riggs BL, Conover CA. Regulation of insulin-like growth factor binding proteins by glucocorticoids in normal human osteoblastlike cells [Abstract]. J Bone Miner Res 1993:173.Google Scholar
  27. 27.
    Bagi CM, DeLeon E, Swett E, et al. Benefit of rhIGF-I/IGFBP-3 treatment on cancellous bone strength in ovariectomized rats. J Bone Miner Res 1993; 8(suppl I):872.Google Scholar
  28. 28.
    Narusawa K, Nakamura T, Matsuoka Y, Lee LJ, Tanaka H, Seino Y. Insulin-like growth factor (IGF-I)/IGF binding protein (IGFBP) 3 complex administration stimulates bone formation in rats [Abstract]. J Bone Miner Res 1993;8:621.Google Scholar
  29. 29.
    Kalu DN, Liu CC, Arjmandi BH, Salerno E, Salih MA, Hollis BW. Growth hormone but not rhIGF-I reversed bone loss due to ovariectomy in rats. J Bone Miner Res 1993;8(suppl 1):s271.Google Scholar
  30. 30.
    Coxam V, Miller MA, Bowman D, et al. Regulation of fetal metatarsal bone growth in the rat. J Bone Miner Res 1993;8(suppl 1):816.Google Scholar
  31. 31.
    Holder AT, Spencer EM, Preece MA. Effect of bovine growth hormone and a partially pure preparation of somatomedin on various growth parameters in hypopituitary dwarf mice. J Endocrinol 1981;89:275–82.PubMedCrossRefGoogle Scholar
  32. 32.
    Scheiller E, Guler HP, Merrywheather J, et al. Growth restoration of insulin-deficient diabetic rats by rhIGF-I. Nature 1986;323:169–70.CrossRefGoogle Scholar
  33. 33.
    Guler HP, Binz K, Eigenmann E, et al Small stature and insulin-like growth factors: prolonged treatment of mini-poodles with rhIGF-I. Acta Endocrinol (Copenh) 1989;121:456–64.Google Scholar
  34. 34.
    Spencer EM, Liu CC, Si EC, et al. In vivo actions of IGF-I on bone formation and resorption in rats. Bone 1991;12:21–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Bagi CM, DeLeon E, Swett E, et al. Benefit of rhIGF-I/IGFBP-3 treatment on cancellous bone strength in ovariectomized rats. J Bone Miner Res 1993; 8(suppl 1):s275.Google Scholar
  36. 36.
    Ammann P, Rissoli R, Meyer JM, et al. Bone mechanical properties and mineral density in IGF-I and/or pamidronate treated ovariectomized rats. J Bone Miner Res 1993;8(suppl 1):612.Google Scholar
  37. 37.
    Ibbotson KJ, Orcutt CM, D’Souza SM, et al. Contrasting effects of parathyroid hormone and IGF-I on an aged ovariectomized rat model of postmenopausal osteoporosis. J Bone Miner Res 1992;7:425–32.PubMedCrossRefGoogle Scholar
  38. 38.
    Bennett AE, Wahner H, Riggs BL, Heintz RL. Insulin-like growth factors I and II: aging and bone density in women. J Clin Endocrinol Metab 1984; 59:701–4.PubMedCrossRefGoogle Scholar
  39. 39.
    Johansson AG, Lindh E, Ljunghall S. Insulin-like growth factor I stimulates bone turnover in osteoporosis. Lancet 1992;339:1619.PubMedCrossRefGoogle Scholar
  40. 40.
    Rubin CD, Reed-Gitomer BY, Sakhaee K, Pak CYC. The comparative effects of recombinant human growth hormone and recombinant human insulin-like growth factor in a patient with osteoporosis. J Bone Miner Res 1992; 7:s403.CrossRefGoogle Scholar
  41. 41.
    Ebling PR, Jones JD, O’Fallon WM, Janes CH, Riggs BL. Short-term effects of recombinant human insulin-like growth factor on bone turnover in normal women. J Clin Endocrinol Metab 1993;77:1384–7.CrossRefGoogle Scholar
  42. 42.
    Shapiro JR, Rachis R, Bellantoni M, Harman SM, Blackman MR. The effect of IGF-I on skeletal turnover in post-menopausal women. J Bone Miner Res 1993;8:s327.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Julie Patterson
  • Jay R. Shapiro
  • Marc R. Blackman

There are no affiliations available

Personalised recommendations