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Insulin enhances the growth of cartilage in organ and tissue cultures of mouse neonatal mandibular condyle

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Summary

Condylar cartilages were cultured in the form of organ cultures on top of collagen sponges in medium containing 2% fetal calf serum and were treated with 3.5–350 nM insulin for 6 days. Doses of 175 nM of insulin caused a marked increase (+96%) in DNA synthesis and in proteoglycan production (+74%), features that manifested themselves structurally by a 60% increase in overall size of the cultured explants. Using a tissue culture system comprised of cartilage progenitor cells, insulin was found to enhance the differentiation of the progenitor cells so that by 6 days in culture and appreciable nodule of differentiated chondrocytes developed. The latter was surrounded by perichondrial cells whereas the extracellular matrix within the newly formed, insulin-induced, nodule reacted positively for cartilagespecific antigens (type II collagen and bone sialoprotein). It is suggested that insulin induces a direct stimulatory effect on progenitor cell proliferation, cartilage differentiation, and extracellular matrix deposition.

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References

  1. Laron Z, Karp M, Pertzelan A, Kauli R (1972) Insulin, growth and growth hormone. Isr J Med Sci 3:440–452

    Google Scholar 

  2. Karp M, Laron Z, Doron M (1973) Insulin secretion in children with constitutional familial short stature. J Pediatr 83:241–246

    CAS  PubMed  Google Scholar 

  3. Laron Z (1981) Insulin as a growth hormone. In: Coller R et al (eds) Pediatric endocrinology. Raven Press, New York, pp 149–165

    Google Scholar 

  4. Salter J, Best C (1953) Insulin as a growth hormone. Br Med J 2:353–356

    CAS  PubMed  Google Scholar 

  5. Susa JB, Widness JA, Hintz R, Liu F, Sehgal P, Schwartz R (1984) Somatomedins and insulin in diabetic pregnancies: effects on fetal macrosomia in the human and rhesus monkey. J Clin Endocrinol Metab 58:1099–1105

    CAS  PubMed  Google Scholar 

  6. Schliwiller E, Guler JP, Merryweather J, Scandella C, Marki W, Zapf J, Froesch ER (1986) Growth retardation of insulindeficient diabetic rats by recombinant human insulin-like growth factor I.Nature 323:169–171

    Google Scholar 

  7. Hock JM, Centrella M, Canalis E (1988) Insulin-like growth factor I has independent effects on bone matrix formation and cell replication. Endocrinology 122:254–263

    CAS  PubMed  Google Scholar 

  8. Strauss DS (1984) Growth stimulation actions of insulin in vitro and in vivo. Endocr Rev 5:356–369

    Google Scholar 

  9. Lebovitz HE, Eisenbarth GS (1975) Hormonal regulation of cartilage growth and metabolism. Vitam Horm 33:575–648

    CAS  PubMed  Google Scholar 

  10. Vetter U, Zapf J, Heit W, Helbing G, Heinze E, Froesch ER, Teller WM (1986) Human fetal and adult chondrocytes. Effects of insulin-like growth factors I and II, insulin and growth hormone on clonal growth. J Clin Invest 77:1903–1908

    CAS  PubMed  Google Scholar 

  11. Stevens RL, Nissley SP, Kimura JH, Rechler MM, Kaplan AJ, Hascall VC (1981) Effects of insulin and multiciplication-stimulating activity on proteoglycan biosynthesis in chondrocytes from the swarm rat chodrosarcoma. J Biol Chem 256: 2045–2052

    CAS  PubMed  Google Scholar 

  12. Bembenek ME, Willis DH, Liberti JP (1982) The effect of insulin on collagen production in isolated chondrocytes. Biochem Biophys Res Commun 106:338–345

    Article  CAS  PubMed  Google Scholar 

  13. Lewinson D, Silbermann M (1986) Parathyroid hormone stimulates proliferation of chondroprogenitor cells in vitro. Calcif Tissue Int 38:155–162

    CAS  PubMed  Google Scholar 

  14. Maor G, Hochberg Z, von der 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

    CAS  PubMed  Google Scholar 

  15. Silbermann M, Maor G (1985) Receptor-mediated glucocorticoid inhibition of cell proliferation in mouse growth cartilage in vitro. Acta Endocrinol 108:343–350

    CAS  PubMed  Google Scholar 

  16. Silbermann M, von der Mark K, Mirsky N, van Menxel M, Lewinson D (1987) Effects of increased doses of 1,25 dihydroxyvitamin D3 on matrix and DNA synthesis in condylar cartilage of suckling mice. Calcif Tissue Int 41:95–104

    CAS  PubMed  Google Scholar 

  17. Maor G, Laron Z, Silbermann M (1989) In vitro effect of insulin-like growth factor I (IGF-I) and insulin on neonatal cartilage progenitor cells. Calcif Tissue Int 44:S11

    Google Scholar 

  18. Silbermann M, Iwamoto M, Kato Y, Suzuki F (1988) TGFβ stimulates DNA synthesis in precartilage cells but depresses alkaline phosphatase activity in chondrocytes and the calcification of the cartilage extracellular matrix in vitro. Calcif Tissue Int 42:S98

    Google Scholar 

  19. Silbermann M, Reddi AH, Hand AR, Leapman R, von der Mark K, Franzen A (1987) Chondroid bone arises from mesenchymal stem cells in organ cultures of mandibular condyles. J Craniofac Genet Dev Biol 7:59–79

    CAS  PubMed  Google Scholar 

  20. Weiss A, von der Mark K, Silbermann M (1986) A tissue culture system supporting cartilage cell differentiation, extracellular mineralization, and subsequent bone formation, using mouse condylar progenitor cells. Cell Diff 19:103–113

    CAS  Google Scholar 

  21. Maor G, von der Mark K, Reddi AH, Heinegard D, Franzen A, Silbermann M (1987) Acceleration of cartilage and bone differentiation on collagen substrate. Collagen Rel Res 7:351–360

    CAS  Google Scholar 

  22. Kato Y, Koike T, Iwamoto M, Kinoshita M, Sato K, Hivaki Y, Suzuki F (1988) Effects of limited exposure of rabbit chondrocytes cultures to parathyroid hormone and dibutyryl adenosine 3′, 5′-monophosphate on cartilage characteristic proteoglycan synthesis. Endocrinology 122:1991–1997

    CAS  PubMed  Google Scholar 

  23. von der Mark H, von der Mark K, Gay S (1976) Immunofluorescence studies of differential collagen synthesis during development of the chick embryo. Dev Biol 48:237–249

    PubMed  Google Scholar 

  24. Holmdahl R, Rubin K, Klareskog L, Larsson E, Wigzell H (1986) Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies. Arthritis Rheum 29:400–410

    CAS  PubMed  Google Scholar 

  25. Franzen A, Heingard D (1985) Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J 232:715–724

    CAS  PubMed  Google Scholar 

  26. Silbermann M, Frommer J (1972) The nature of endochondral ossification in the mandibular condyle of the mouse. Anat Rec 172:659–668

    Article  CAS  PubMed  Google Scholar 

  27. Silbermann M, Tenenbaum H, Livne E, Leapman R, von der Mark K, Reddi AH (1987) The in vitro behavior of fetal condylar cartilage in serum-free hormone-supplemented medium. Bone 8:117–126

    Article  CAS  PubMed  Google Scholar 

  28. Copray JCVM, Brouwer N, Prins APA, Jansen HWB (1988) Effects of polypeptide growth factors on mandibular condylar cartilage of the rat in vitro. J Biol Buccule 16:109–117

    CAS  Google Scholar 

  29. Maor G, Laron Z, Ashot R, Silbermann M (in press) The growth of the murine-derived neonatal mandibular condyle is dependent on the paracrine activity of insulin-like growth factor I (IGF-I). Endocrinology

  30. Goldstein RH, Poliks CF, Pilch PF, Smith BD, Fine A (1989) Stimulation of collagen formation by insulin and insulin-like growth factor I cultures of human lung fibroblasts. Endocrinology 124:964–970

    CAS  PubMed  Google Scholar 

  31. Okajima T, Nakamura K, Zhang H, Ling N, Tanabe T, Yasuda T, Rosenfeld RG (1992) Sensitive colorimetric bioassays for insulin-like growth factor (IGF) stimulation of cell proliferation and glucose consumption: use in studies of IGF analysis. Endocrinology 130:2201–2212

    Article  CAS  PubMed  Google Scholar 

  32. Kemp SF, Mutchinic M, Hintz RL (1984) Hormonal control of protein synthesis in chick chondrocytes: a comparison of effects of insulin, somatomedin C and triiodothyronine. Acta Endocrinol 107:179–184

    CAS  PubMed  Google Scholar 

  33. Alarid ET, Schlechter NL, Russell SM, Nicoll CS (1992) Evidence suggesting that insulin-like growth factor I is necessary for the tropic effects of insulin on cartilage growth in vivo. Endocrinology 139:2305–2309

    Google Scholar 

  34. Froger-Gaillard B, Hossenlopp P, Adolphe M, Binoux M (1989) Production of insulin-like growth factors and their binding proteins by rabbit articular chondrocytes: relationship with cell multiplication. Endocrinology 124:2365–2372

    CAS  PubMed  Google Scholar 

  35. Flier JS, Usher P, Moses AC (1986) Monoclonal antibody to the type 1 insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts. Proc Natl Acad Sci USA 83:664–668

    CAS  PubMed  Google Scholar 

  36. Zapf J, Schmidt CH, Froesch ER (1984) Biological and immunological properties of insulin-like growth factor (IGF) I and II. Clin Endocrinol Metab 13:3–30

    Article  CAS  PubMed  Google Scholar 

  37. Ullrich A, Bell JR, Chen EY, Herrera R, Petruzelli LM, Dull TJ, Gray A, Cousseus L, Liao YC, Tsubokawa M, Mason A, Seeburg PH, Grunfeld C, Rosen OM, Ramachandran J (1986) Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313:756–761

    Google Scholar 

  38. Roth RA (1988) Structure of the receptor for insulin-like growth factor II: the puzzle amplified. Science 239:1269–1271

    CAS  PubMed  Google Scholar 

  39. Morgan DO, Jarnagin K, Roth RA (1986) Purification characterization of the receptor for insulin-like growth factor I. Biochemistry 25:5560–5564

    CAS  PubMed  Google Scholar 

  40. Rosen OM (1987) After insulin binds. Science 237:1452–1458

    CAS  PubMed  Google Scholar 

  41. Winter SJ, Turvey A, Forsyth IA (1989) Stimulation of DNA synthesis in cultures of ovine mamary epithelial cells by insulin and insulin-like growth factors. J Endocrinol 123:319–326

    Google Scholar 

  42. Kono T, Robinson FW, Blevins TL, Ezaki O (1982) Evidence that translocation of the glucose transport activity is the major mechanism of insulin action on glucose transport in fat cells. J Biol Chem 257:10942–10947

    CAS  PubMed  Google Scholar 

  43. Mortimore GE, Mondon CE (1970) Inhibition by insulin of valine turnover in liver. J Biol Chem 245:2375–2383

    CAS  PubMed  Google Scholar 

  44. Draznin B, Trowbridge M (1982) Inhibition of intracellular proteolysis by insulin in isolated rat hepatocytes. J Biol Chem 257: 11988–11993

    CAS  PubMed  Google Scholar 

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Maor, G., Silbermann, M., von der Mark, K. et al. Insulin enhances the growth of cartilage in organ and tissue cultures of mouse neonatal mandibular condyle. Calcif Tissue Int 52, 291–299 (1993). https://doi.org/10.1007/BF00296654

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  • DOI: https://doi.org/10.1007/BF00296654

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