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. 1992 Apr;51(4):440–447. doi: 10.1136/ard.51.4.440

Upregulation of insulin-like growth factor I gene expression in the lesions of osteoarthritic human articular cartilage.

J F Middleton 1, J A Tyler 1
PMCID: PMC1004688  PMID: 1586240

Abstract

Expression of insulin-like growth factor I (IGF-I)mRNA and IGF-I protein was studied in human osteoarthritic and young articular cartilage by in situ hybridisation and immunohistochemistry. In situ hybridisation showed that relatively low amounts of IGF-I mRNA signal were present in anatomically normal regions of osteoarthritic and young cartilage. In fibrillated osteoarthritic cartilage, however, the signal intensity was significantly higher than in non-fibrillated cartilage. Particularly high levels of IGF-I mRNA were present in the surface cell clones of more advanced lesions, the amount of signal being about four to five times greater than in anatomically normal cartilage. The amount of message varied with cartilage depth. In young cartilage there was less IGF-I mRNA in the superficial zone than in the middle and deep zones. In fibrillated regions of osteoarthritic joints the amount of message in surface cells was greater than in deeper regions. A specific human IGF-I antibody was used to show the presence intracellularly of IGF-I protein in osteoarthritic and young cartilage. Raised levels of IGF-I message in osteoarthritic chondrocytes may represent an attempt at increased matrix repair, operating by an autocrine/paracrine mechanism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arend W. P., Dayer J. M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990 Mar;33(3):305–315. doi: 10.1002/art.1780330302. [DOI] [PubMed] [Google Scholar]
  2. Brahic M., Haase A. T. Detection of viral sequences of low reiteration frequency by in situ hybridization. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6125–6129. doi: 10.1073/pnas.75.12.6125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burch W. M., Weir S., Van Wyk J. J. Embryonic chick cartilage produces its own somatomedin-like peptide to stimulate cartilage growth in vitro. Endocrinology. 1986 Sep;119(3):1370–1376. doi: 10.1210/endo-119-3-1370. [DOI] [PubMed] [Google Scholar]
  4. 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 Jan;122(1):22–27. doi: 10.1210/endo-122-1-22. [DOI] [PubMed] [Google Scholar]
  5. Clemmons D. R., Underwood L. E., Van Wyk J. J. Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts. J Clin Invest. 1981 Jan;67(1):10–19. doi: 10.1172/JCI110001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  7. D'Ercole A. J., Applewhite G. T., Underwood L. E. Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol. 1980 Mar 15;75(2):315–328. doi: 10.1016/0012-1606(80)90166-9. [DOI] [PubMed] [Google Scholar]
  8. D'Ercole A. J., Hill D. J., Strain A. J., Underwood L. E. Tissue and plasma somatomedin-C/insulin-like growth factor I concentrations in the human fetus during the first half of gestation. Pediatr Res. 1986 Mar;20(3):253–255. doi: 10.1203/00006450-198603000-00011. [DOI] [PubMed] [Google Scholar]
  9. D'Ercole A. J. Somatomedins/insulin-like growth factors and fetal growth. J Dev Physiol. 1987 Dec;9(6):481–495. [PubMed] [Google Scholar]
  10. D'Ercole A. J., Stiles A. D., Underwood L. E. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Daughaday W. H., Parker K. A., Borowsky S., Trivedi B., Kapadia M. Measurement of somatomedin-related peptides in fetal, neonatal, and maternal rat serum by insulin-like growth factor (IGF) I radioimmunoassay, IGF-II radioreceptor assay (RRA), and multiplication-stimulating activity RRA after acid-ethanol extraction. Endocrinology. 1982 Feb;110(2):575–581. doi: 10.1210/endo-110-2-575. [DOI] [PubMed] [Google Scholar]
  12. Daughaday W. H., Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989 Feb;10(1):68–91. doi: 10.1210/edrv-10-1-68. [DOI] [PubMed] [Google Scholar]
  13. Eyre D. R., McDevitt C. A., Billingham M. E., Muir H. Biosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthrosis. Biochem J. 1980 Jun 15;188(3):823–837. doi: 10.1042/bj1880823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Froesch E. R., Schmid C., Schwander J., Zapf J. Actions of insulin-like growth factors. Annu Rev Physiol. 1985;47:443–467. doi: 10.1146/annurev.ph.47.030185.002303. [DOI] [PubMed] [Google Scholar]
  15. Froger-Gaillard B., Hossenlopp P., Adolphe M., Binoux M. Production of insulin-like growth factors and their binding proteins by rabbit articular chondrocytes: relationships with cell multiplication. Endocrinology. 1989 May;124(5):2365–2372. doi: 10.1210/endo-124-5-2365. [DOI] [PubMed] [Google Scholar]
  16. Funa K., Steinholtz L., Nou E., Bergh J. Increased expression of N-myc in human small cell lung cancer biopsies predicts lack of response to chemotherapy and poor prognosis. Am J Clin Pathol. 1987 Aug;88(2):216–220. doi: 10.1093/ajcp/88.2.216. [DOI] [PubMed] [Google Scholar]
  17. Furlanetto R. W., Underwood L. E., Van Wyk J. J., D'Ercole A. J. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest. 1977 Sep;60(3):648–657. doi: 10.1172/JCI108816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Guenther H. L., Guenther H. E., Froesch E. R., Fleisch H. Effect of insulin-like growth factor on collagen and glycosaminoglycan synthesis by rabbit articular chondrocytes in culture. Experientia. 1982 Aug 15;38(8):979–981. doi: 10.1007/BF01953688. [DOI] [PubMed] [Google Scholar]
  19. Guerne P. A., Carson D. A., Lotz M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J Immunol. 1990 Jan 15;144(2):499–505. [PubMed] [Google Scholar]
  20. Han V. K., D'Ercole A. J., Lund P. K. Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science. 1987 Apr 10;236(4798):193–197. doi: 10.1126/science.3563497. [DOI] [PubMed] [Google Scholar]
  21. Han V. K., Lund P. K., Lee D. C., D'Ercole A. J. Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus: identification, characterization, and tissue distribution. J Clin Endocrinol Metab. 1988 Feb;66(2):422–429. doi: 10.1210/jcem-66-2-422. [DOI] [PubMed] [Google Scholar]
  22. Jansen J., van Buul-Offers S. C., Hoogerbrugge C. M., de Poorter T. L., Corvol M. T., Van den Brande J. L. Characterization of specific insulin-like growth factor (IGF)-I and IGF-II receptors on cultured rabbit articular chondrocyte membranes. J Endocrinol. 1989 Feb;120(2):245–249. doi: 10.1677/joe.0.1200245. [DOI] [PubMed] [Google Scholar]
  23. Jansen M., van Schaik F. M., Ricker A. T., Bullock B., Woods D. E., Gabbay K. H., Nussbaum A. L., Sussenbach J. S., Van den Brande J. L. Sequence of cDNA encoding human insulin-like growth factor I precursor. Nature. 1983 Dec 8;306(5943):609–611. doi: 10.1038/306609a0. [DOI] [PubMed] [Google Scholar]
  24. Lund P. K., Moats-Staats B. M., Hynes M. A., Simmons J. G., Jansen M., D'Ercole A. J., Van Wyk J. J. Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem. 1986 Nov 5;261(31):14539–14544. [PubMed] [Google Scholar]
  25. Mankin H. J., Dorfman H., Lippiello L., Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971 Apr;53(3):523–537. [PubMed] [Google Scholar]
  26. McQuillan D. J., Handley C. J., Campbell M. A., Bolis S., Milway V. E., Herington A. C. Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage. Biochem J. 1986 Dec 1;240(2):423–430. doi: 10.1042/bj2400423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nilsson A., Isgaard J., Lindahl A., Dahlström A., Skottner A., Isaksson O. G. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science. 1986 Aug 1;233(4763):571–574. doi: 10.1126/science.3523759. [DOI] [PubMed] [Google Scholar]
  28. Ollivierre F., Gubler U., Towle C. A., Laurencin C., Treadwell B. V. Expression of IL-1 genes in human and bovine chondrocytes: a mechanism for autocrine control of cartilage matrix degradation. Biochem Biophys Res Commun. 1986 Dec 30;141(3):904–911. doi: 10.1016/s0006-291x(86)80128-0. [DOI] [PubMed] [Google Scholar]
  29. Pelletier J. P., Martel-Pelletier J. Evidence for the involvement of interleukin 1 in human osteoarthritic cartilage degradation: protective effect of NSAID. J Rheumatol Suppl. 1989 Aug;18:19–27. [PubMed] [Google Scholar]
  30. Rinderknecht E., Humbel R. E. Primary structure of human insulin-like growth factor II. FEBS Lett. 1978 May 15;89(2):283–286. doi: 10.1016/0014-5793(78)80237-3. [DOI] [PubMed] [Google Scholar]
  31. Rinderknecht E., Humbel R. E. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem. 1978 Apr 25;253(8):2769–2776. [PubMed] [Google Scholar]
  32. Rotwein P. Two insulin-like growth factor I messenger RNAs are expressed in human liver. Proc Natl Acad Sci U S A. 1986 Jan;83(1):77–81. doi: 10.1073/pnas.83.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ryu J., Treadwell B. V., Mankin H. J. Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage. Arthritis Rheum. 1984 Jan;27(1):49–57. doi: 10.1002/art.1780270109. [DOI] [PubMed] [Google Scholar]
  34. SALMON W. D., Jr, DAUGHADAY W. H. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med. 1957 Jun;49(6):825–836. [PubMed] [Google Scholar]
  35. Schalkwijk J., Joosten L. A., van den Berg W. B., van Wyk J. J., van de Putte L. B. Insulin-like growth factor stimulation of chondrocyte proteoglycan synthesis by human synovial fluid. Arthritis Rheum. 1989 Jan;32(1):66–71. doi: 10.1002/anr.1780320111. [DOI] [PubMed] [Google Scholar]
  36. Schoenle E., Zapf J., Humbel R. E., Froesch E. R. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature. 1982 Mar 18;296(5854):252–253. doi: 10.1038/296252a0. [DOI] [PubMed] [Google Scholar]
  37. Tourtellotte W. W., Verity A. N., Schmid P., Martinez S., Shapshak P. Covalent binding of formalin fixed paraffin embedded brain tissue sections to glass slides suitable for in situ hybridization. J Virol Methods. 1987 Feb;15(2):87–99. doi: 10.1016/0166-0934(87)90052-8. [DOI] [PubMed] [Google Scholar]
  38. Trippel S. B., Corvol M. T., Dumontier M. F., Rappaport R., Hung H. H., Mankin H. J. Effect of somatomedin-C/insulin-like growth factor I and growth hormone on cultured growth plate and articular chondrocytes. Pediatr Res. 1989 Jan;25(1):76–82. doi: 10.1203/00006450-198901000-00017. [DOI] [PubMed] [Google Scholar]
  39. Tyler J. A. Insulin-like growth factor 1 can decrease degradation and promote synthesis of proteoglycan in cartilage exposed to cytokines. Biochem J. 1989 Jun 1;260(2):543–548. doi: 10.1042/bj2600543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vetter U., Helbing G., Heit W., Pirsig W., Sterzig K., Heinze E. Clonal proliferation and cell density of chondrocytes isolated from human fetal epiphyseal, human adult articular and nasal septal cartilage. Influence of hormones and growth factors. Growth. 1985 Summer;49(2):229–245. [PubMed] [Google Scholar]
  41. Watanabe N., Rosenfeld R. G., Hintz R. L., Dollar L. A., Smith R. L. Characterization of a specific insulin-like growth factor-I/somatomedin-C receptor on high density, primary monolayer cultures of bovine articular chondrocytes: regulation of receptor concentration by somatomedin, insulin and growth hormone. J Endocrinol. 1985 Nov;107(2):275–283. doi: 10.1677/joe.0.1070275. [DOI] [PubMed] [Google Scholar]
  42. Wood D. D., Ihrie E. J., Dinarello C. A., Cohen P. L. Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum. 1983 Aug;26(8):975–983. doi: 10.1002/art.1780260806. [DOI] [PubMed] [Google Scholar]

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