Skip to main content
SpringerLink
Log in

Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Summary

In this study we investigated the direct, shortterm effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P<0.001, n=15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P<0.05, n=10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P=0.07, n=9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P=0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Isaksson OG, Lindhal A, Nilsson A, Isgaard J (1987) Mechanisms of the stimulatory effects of growth hormone on longitudinal bone growth. Endocr Rev 8:426–438

    Google Scholar 

  2. Russell SM, Spencer EM (1985) Local injections of human or rat growth hormone or of purified human somatomedin-C stimulate unilateral tibial epiphyseal growth in hypophysectomized rats. Endocrinology 116:2563–2568

    Google Scholar 

  3. Brixen K, Nielsen HK, Mosekilde L, Flyvbjerg A (1990) A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers. J Bone Miner Res 5:609–618

    Google Scholar 

  4. Marcus R, Butterfield G, Holloway L, Baylink DJ, Hintz RL, Sherman BM (1990) Effects of short-term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab 70:519–527

    Google Scholar 

  5. Slootweg MC, Buul-Offers SC, Herrmann-Erlee MPM, Meer JM, Duursma SA (1988) Growth hormone is mitogenic for fetal mouse osteoblasts but not for undifferentiated bone cells. Endocrinology 116:11–13

    Google Scholar 

  6. Ernst M, Froesch ER (1988) Growth hormone-dependent stimulation of osteoblast-like cells in serum-free cultures via local synthesis of insulin-like growth factor 1. Biochim Biophys Res Commun 151:142–147

    Google Scholar 

  7. Maor G, Hochberg Z, Mark K, Heinegard D, Silbermann M (1989) Human growth hormone enhances chondrogenesis and osteogenesis in a tissue culture system of chondroprogenitor cells. Endocrinology 125:1239–1245

    Google Scholar 

  8. Scheven BAA, Hamilton NJ, Fakkeldij TMV, Duursma SA (1991) Effects of recombinant human insulin-like growth factor I and II (IGF-I/II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cells and human osteogenic sarcoma cells. Growth Regulation 1:160–167

    Google Scholar 

  9. Chenu C, Valentin-Optan A, Chavassieux P, Saez S, Meunier PJ, Delmas PD (1990) Insulin-like growth factor 1 hormonal regulation by growth hormone and by 1,25(OH)2D3 and activity on human osteoblast-like cells in short-term cultures Bone 11:81–86

    Google Scholar 

  10. Daughaday WH, Rotwein P (1989) Insulin-like growth factors I and II peptide, messenger ribonucleic acid and gene structure, serum and tissue concentrations. Endocr Rev 10:68–91

    Google Scholar 

  11. Canalis E, McCarthy TL, Centrella M (1989) The role of skeletal growth factors in skeletal remodeling. Endocrinol Metab Clin N Am 18:903–918

    Google Scholar 

  12. Wergedal JE, Mohan S, Lundy M, Baylink DJ (1990) Skeletal growth factors 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 

  13. Hassager C, Spencer EM, Fitzpatrick LA, Riggs BL (1991) Insulin-like growth factor binding protein secretion in osteoblast-like cells is cell line specific. J Bone Miner Res 6(suppl 1): s146

  14. Blum WF, Ranke MB, Kietzmann K, Gauggel E, Zeisel HJ, Bierich JR (1990) A specific radioimmunoassay for the growth hormone(GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency. J Clin Endocrinol Metab 70:1292–1298

    Google Scholar 

  15. Baxter RC, Martin JL (1989) Binding proteins for the insulin-like growth factors: structure, regulation and function Prog Growth Factor Res 1:49–68

    Google Scholar 

  16. Robey PG, Termine JD (1985) Human bone cells in vitro. Calcif Tissue Int 37:453–460

    Google Scholar 

  17. Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, Riggs BL (1988) Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241:84–86

    Google Scholar 

  18. Egsmose C, Daugaard H, Lund B, (1989) Determination of bone Gla protein (osteocalcin) by enzyme-linked immunosorbent assay. Clin Chim Acta 184:279–288

    Google Scholar 

  19. Melkko J, Niemi S, Risteli L, Risteli J (1990) Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem 36:1328–1332

    Google Scholar 

  20. Risteli J, Niemi S, Trivedi P, Maentausta O, Mowat OP, Risteli L (1988) Rapid equilibrium radioimmunoassay for the aminoterminal propeptide of human type III procollagen. Clin Chem 34:715–718

    Google Scholar 

  21. Blum WF, Ranke MB, Bierich JR (1988) A specific radioimmunoassay for insulin-like growth factor II: the interference of IGF binding proteins can be blocked by excess IGF-I. Acta Endocrinol 118:374–380

    Google Scholar 

  22. Blum WF, Breier B, Gluckman P, Ranke MB (1992) A novel IGFBP-blocked IGF-I RIA that measured what it pretends to measure: IGF-I. Acta Endocrinol 126 (suppl 4):76

    Google Scholar 

  23. Feldman HA (1988) Families of lines: random effects in linear regression analysis. J Appl Physiol 64:1721–1732

    Google Scholar 

  24. Cook JJ, Haynes KM, Werther GA (1988) Mitogenic effects of growth hormone in cultured human fibroblasts. J Clin Invest 81:206–212

    Google Scholar 

  25. Brixen K, Risteli J, Risteli L, Nielsen HK, Flyvbjerg A, Eriksen EF, Mosekilde L (1992) Effects of short course of growth hormone treatment on type I and type III procollagen propeptides in serum in normal human volunteers. Eur J Exp Musculoskel Res 1:5–10

    Google Scholar 

  26. Rodan GA, Rodan SB (1983) Expression of the osteoblastic phenotype, In: Peck WA (ed) Bone and mineral research, annual 1. Elsevier, Amsterdam, p 244

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  29. Mohan S, Dequeker J, Van den Eyned R, Peeters J, Aerssens J, Baylink D (1991) Increased IGF-I and IGF-II in bone from patients with osteoarthritis. J Bone Miner Res 6(suppl 1): s131

  30. Slootweg MC, Vangenesen ST, Otte AP, Duursma SA, Kruijer W (1990) Activation of mouse osteoblast growth hormone receptor. C-fos oncogene expression expression independent of phosphoinositide breakdown and cyclic AMP. J Mol Endocrinol 4:265–274

    Google Scholar 

  31. Murphy LJ, Bell GI, Friesen HG (1987) Growth hormone stimulates sequential induction of c-myc and insulin-like growth factor I expression in vivo. Endocrinology 120:1806–1812

    Google Scholar 

  32. Barnard R, Ng NW, Martin TJ, Waters MJ (1991) Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. Endocrinology 128:1459–1464

    Google Scholar 

  33. Green H, Morikawa M, Nixon T (1985) A dual effector theory of growth-hormone action. Differentiation 29:195–198

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Aarhus Bone and Mineral Research Group, University Department of Endocrinology, Aarhus amtssygehus, DK-8000, Aarhus C, Denmark

    M. Kassem, L. Mosekilde & E. F. Eriksen

  2. Universitäts Kinderklinik, Tübingen, Germany

    W. Blum

  3. Collagen Research Unit, University of Oulu, Oulu, Finland

    J. Ristelli

Authors
  1. M. Kassem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Blum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Ristelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Mosekilde
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. F. Eriksen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kassem, M., Blum, W., Ristelli, J. et al. Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro . Calcif Tissue Int 52, 222–226 (1993). https://doi.org/10.1007/BF00298723

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00298723

Key words

Search

Navigation