• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Nov 1995; 96(5): 2454–2460.
PMCID: PMC185898

Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation.


Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli beta-galactosidase marker gene, and a third vector (Ad.RSV hIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 10(3) plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli beta-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface of osteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining of the cartilage organ cultures for E. coli beta-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-1ra and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-1ra-treated cartilage samples were resistant to IL1-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-1-induced extracellular matrix degradation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Steinberg JJ, Sledge CB. Chondrocyte mediated cartilage degradation: regulation by prostaglandin E2, cyclic AMP and interferon alpha. J Rheumatol Suppl. 1991 Feb;27:63–65. [PubMed]
  • Dodge GR, Poole AR. Immunohistochemical detection and immunochemical analysis of type II collagen degradation in human normal, rheumatoid, and osteoarthritic articular cartilages and in explants of bovine articular cartilage cultured with interleukin 1. J Clin Invest. 1989 Feb;83(2):647–661. [PMC free article] [PubMed]
  • Fell HB, Jubb RW. The effect of synovial tissue on the breakdown of articular cartilage in organ culture. Arthritis Rheum. 1977 Sep-Oct;20(7):1359–1371. [PubMed]
  • Hamerman D. Cartilage changes in the rheumatoid joint. Clin Orthop Relat Res. 1969 May-Jun;64:91–97. [PubMed]
  • Bora FW, Jr, Miller G. Joint physiology, cartilage metabolism, and the etiology of osteoarthritis. Hand Clin. 1987 Aug;3(3):325–336. [PubMed]
  • Bland JH, Cooper SM. Osteoarthritis: a review of the cell biology involved and evidence for reversibility. Management rationally related to known genesis and pathophysiology. Semin Arthritis Rheum. 1984 Nov;14(2):106–133. [PubMed]
  • Bandara G, Robbins PD, Georgescu HI, Mueller GM, Glorioso JC, Evans CH. Gene transfer to synoviocytes: prospects for gene treatment of arthritis. DNA Cell Biol. 1992 Apr;11(3):227–231. [PubMed]
  • Bandara G, Mueller GM, Galea-Lauri J, Tindal MH, Georgescu HI, Suchanek MK, Hung GL, Glorioso JC, Robbins PD, Evans CH. Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10764–10768. [PMC free article] [PubMed]
  • Roessler BJ, Allen ED, Wilson JM, Hartman JW, Davidson BL. Adenoviral-mediated gene transfer to rabbit synovium in vivo. J Clin Invest. 1993 Aug;92(2):1085–1092. [PMC free article] [PubMed]
  • Roessler BJ, Hartman JW, Vallance DK, Latta JM, Janich SL, Davidson BL. Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector. Hum Gene Ther. 1995 Mar;6(3):307–316. [PubMed]
  • Hung GL, Galea-Lauri J, Mueller GM, Georgescu HI, Larkin LA, Suchanek MK, Tindal MH, Robbins PD, Evans CH. Suppression of intra-articular responses to interleukin-1 by transfer of the interleukin-1 receptor antagonist gene to synovium. Gene Ther. 1994 Jan;1(1):64–69. [PubMed]
  • Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994 Oct 6;331(14):889–895. [PubMed]
  • Dinarello CA. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. [PubMed]
  • Arend WP, Dayer JM. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990 Mar;33(3):305–315. [PubMed]
  • Smith RJ, Rohloff NA, Sam LM, Justen JM, Deibel MR, Cornette JC. Recombinant human interleukin-1 alpha and recombinant human interleukin-1 beta stimulate cartilage matrix degradation and inhibit glycosaminoglycan synthesis. Inflammation. 1989 Aug;13(4):367–382. [PubMed]
  • Kumkumian GK, Lafyatis R, Remmers EF, Case JP, Kim SJ, Wilder RL. Platelet-derived growth factor and IL-1 interactions in rheumatoid arthritis. Regulation of synoviocyte proliferation, prostaglandin production, and collagenase transcription. J Immunol. 1989 Aug 1;143(3):833–837. [PubMed]
  • Gilman SC. Activation of rabbit articular chondrocytes by recombinant human cytokines. J Rheumatol. 1987 Oct;14(5):1002–1007. [PubMed]
  • Dayer JM, de Rochemonteix B, Burrus B, Demczuk S, Dinarello CA. Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J Clin Invest. 1986 Feb;77(2):645–648. [PMC free article] [PubMed]
  • Dinarello CA, Thompson RC. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today. 1991 Nov;12(11):404–410. [PubMed]
  • Schwab JH, Anderle SK, Brown RR, Dalldorf FG, Thompson RC. Pro- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats. Infect Immun. 1991 Dec;59(12):4436–4442. [PMC free article] [PubMed]
  • Dripps DJ, Brandhuber BJ, Thompson RC, Eisenberg SP. Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J Biol Chem. 1991 Jun 5;266(16):10331–10336. [PubMed]
  • Arend WP. Interleukin-1 receptor antagonist. Adv Immunol. 1993;54:167–227. [PubMed]
  • Hurwitz DR, Chinnadurai G. Evidence that a second tumor antigen coded by adenovirus early gene region E1a is required for efficient cell transformation. Proc Natl Acad Sci U S A. 1985 Jan;82(1):163–167. [PMC free article] [PubMed]
  • Walsh C, Cepko CL. Clonally related cortical cells show several migration patterns. Science. 1988 Sep 9;241(4871):1342–1345. [PubMed]
  • Weiss C, Mirow S. An ultrastructural study of osteoarthritis changes in the articular cartilage of human knees. J Bone Joint Surg Am. 1972 Jul;54(5):954–972. [PubMed]
  • Wooley PH, Whalen JD, Chapman DL, Berger AE, Richard KA, Aspar DG, Staite ND. The effect of an interleukin-1 receptor antagonist protein on type II collagen-induced arthritis and antigen-induced arthritis in mice. Arthritis Rheum. 1993 Sep;36(9):1305–1314. [PubMed]
  • Chesterman PJ, Smith AU. Homotransplantation of articular cartilage and isolated chondrocytes. An experimental study in rabbits. J Bone Joint Surg Br. 1968 Feb;50(1):184–197. [PubMed]
  • Green WT., Jr Articular cartilage repair. Behavior of rabbit chondrocytes during tissue culture and subsequent allografting. Clin Orthop Relat Res. 1977 May;(124):237–250. [PubMed]
  • Aston JE, Bentley G. Repair of articular surfaces by allografts of articular and growth-plate cartilage. J Bone Joint Surg Br. 1986 Jan;68(1):29–35. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...