Calcified Tissue International

, Volume 35, Issue 1, pp 767–772 | Cite as

Xenografts of articular chondrocytes in the nude mouse

  • Jack M. Lipman
  • Cahir A. McDevitt
  • Leon Sokoloff
Laboratory Investigations


Subcutaneous transplantation of articular chondrocytes isolated enzymatically from immature rabbits and dogs into athymic (nu/nu) mice resulted in the formation of hyaline cartilaginous nodules. Graft rejection was seen when the cells were injected into heterozygous (nu/+) mice. Radiosulfate-labeled proteoglycan extracted from the xenografts had a high buoyant density and was digested by chondroitinase ABC. A monomeric preparation of proteoglycan (A1-D1) contained a small quantity of aggregate as assessed by gel chromatography and gel electrophoresis. Almost no incorporation of3H-thymidine was found by autoradiography. The matrix did not become calcified over the course of 42 days. The nude mouse system lends itself to testing a variety of problems in the biology of cartilage. These include the redifferentiation of chondrocytes following dedifferentiation in vitro. Species differences were found in this regard. The nodules formed by rabbit articular chondrocytes, grown in monolayer culture for up to 14 days, had a hyaline chondroid character. Dog chondrocytes that had “dedifferentiated,” during 14 days of culture prior to transplantation, formed a graft that had a sparse fibrous rather than hyaline matrix.

Key words

Articular chondrocytes Nude mouse Xenograft Dedifferentiation 


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  1. 1.
    Green WT Jr (1977) Articular cartilage repair. Behavior of rabbit chondrocytes during tissue culture and subsequent allografting. Clin Orthop 124:237–250.PubMedGoogle Scholar
  2. 2.
    Elves MW (1978) The immunobiology of joints. In: Sokoloff L (ed) The joints and synovial fluid, vol 1. Academic Press, New York, pp 331–406Google Scholar
  3. 3.
    Bentley G, Smith AU, Mukerjhee R (1978) Isolated epiphyseal chondrocyte allografts into joint surfaces. An experimental study in rabbits. Ann Rheum Dis 37:449–458PubMedCrossRefGoogle Scholar
  4. 4.
    Thyberg J, Moskalewski S (1979) Bone formation in cartilage produced by transplanted epiphyseal chondrocytes. Cell Tissue Res 204:77–94CrossRefPubMedGoogle Scholar
  5. 5.
    Loeb L (1926) Autotransplantation and homoiotransplantation of cartilage in the guinea-pig. Am J Pathol 2:111–122Google Scholar
  6. 6.
    Heyner S (1969) The significance of intercellular matrix in the survival of cartilage allografts. Transplantation 8:666–677PubMedGoogle Scholar
  7. 7.
    London WT, Fucillo DA, Anderson B, Sever JL (1970) Concentration of rubella virus in chondrocytes of congenitally infected rabbits. Nature 226:172–173CrossRefPubMedGoogle Scholar
  8. 8.
    Malseed ZM, Heyner S (1976) Antigenic profile of the rat chondrocytes. Arthritis Rheum 19:223–231PubMedGoogle Scholar
  9. 9.
    Gertzbein SD, Tait JH, Devlin S, Rogargues S (1977) The antigenicity of chondrocytes. Immunology 33:141–145PubMedGoogle Scholar
  10. 10.
    Urist MR, Adam T (1968) Cartilage or bone induction by articular cartilage. Observations with radioisotope labelling techniques. J Bone Joint Surg 50B:198–215Google Scholar
  11. 11.
    Kaminski J, Kaminski G, Moskalewski S (1980) Species differences in the ability of isolated eipiphyseal chondrocytes to hypertrophy after transplantation into the wall of the syrian hamster cheek pouch. Folia Biol (Krakow) 28:27–38Google Scholar
  12. 12.
    Gullino PM, Ediger RD, Giovanella B, Merchant B, Outzen HC, Reed ND, Wortis HH (1976) Guide for the care and use of the nude (thymus-deficient) mouse in biomedical research. ILAR News 19 (2):M1-M20Google Scholar
  13. 13.
    Sokoloff L, Malemud CJ, Green WT Jr (1970) Sulfate incorporation by articular chondrocytes in monolayer culture. Arthritis Rheum 13:118–124PubMedGoogle Scholar
  14. 14.
    Green WT Jr (1971) Behavior of articular chondrocytes in cell culture. Clin Orthop 75:248–260PubMedGoogle Scholar
  15. 15.
    Lillie RD (1965) Histopathologic technique and practical histochemistry, 3rd edn. McGraw-Hill, New YorkGoogle Scholar
  16. 16.
    Krystal G, Morris GM, Lipman JM, Sokoloff L (1983) DNA repair by articular chondrocytes. I. Unscheduled DNA synthesis following ultraviolet irradiation in monolayer culture. Mech Ageing Dev 21:83–96.CrossRefPubMedGoogle Scholar
  17. 17.
    Prins APA, Lipman JM, McDevitt CA, Sokoloff L (1982) The effect of purified growth factors on rabbit articular chondrocytes in monolayer culture. 2. Sulfated proteoglycans. Arthritis Rheum 16:1228–1238Google Scholar
  18. 18.
    McDevitt CA (1981) The proteoglycans of hyaline cartilage and the intervertebral disc in ageing and osteoarthritis. In: Glynn LE (ed) Handbook of inflammation, vol 3: Tissue repair and remodeling. Elsevier-Holland, Amsterdam, pp 111–143Google Scholar
  19. 19.
    McDevitt CA, Muir H (1971) Gel-electrophoresis of proteoglycans and glycosaminoglycans on large pore composite polyacrylamide—agarose gels. Anal Biochem 44:612–622CrossRefPubMedGoogle Scholar
  20. 20.
    Oike YO, Kimata K, Shinomura T, Nakazawa K, Suzuki S (1980) Structural analysis of chick embryo cartilage proteoglycan by selective degradation with chondroitin lyases (chondroitinases) and endo-β-D-galactosidase (keratanase). Biochem J 191:193–207PubMedGoogle Scholar
  21. 21.
    Dahlberg A, Dingman CW, Peacock AC (1969) Electrophoretic characterization of bacterial polyribosomes in agarose—acrylamide gels. J Mol Biol 41:139–147CrossRefPubMedGoogle Scholar
  22. 22.
    Moskalewski S, Kawiak J (1965) Cartilage formation after homotransplantation of isolated chondrocytes. Transplantation 3:737–747PubMedGoogle Scholar
  23. 23.
    Chesterman PV, Smith AU (1968) Homotransplantation of articular cartilage and isolated chondrocytes. J Bone Joint Surg 50B:184–215Google Scholar
  24. 24.
    Moskalewski S (1981) The elastogenetic process in transplants and cultures of isolated auricular chondrocytes. Connect Tissue Res 8:171–181PubMedGoogle Scholar
  25. 25.
    Gay S (1983) Immunology of collagen. In: Wagner BM, Fleischmajer RF (eds) Connective tissue and diseases of connective tissue. IAP Monograph. Williams and Wilkins, Baltimore pp 120–128Google Scholar
  26. 26.
    Poole AR, Pidoux I, Reiner A, Tangl H, Choi H, Rosenberg L (1980) Localization of proteoglycan monomer and link protein in the matrix of bovine articular cartilage: an immunohistochemical study. J Histochem Cytochem 28:621–635PubMedGoogle Scholar
  27. 27.
    Sokoloff L (1980) In vitro culture of joints and articular tissues. In: Sokoloff L (ed) The joints and synovial fluid, vol 2. Academic Press, New York, pp 1–26Google Scholar
  28. 28.
    Srivastava VML, Malemud CJ, Sokoloff L (1974) Chondroid expression by lapine articular chondrocytes in spinner culture following monolayer growth. Connect Tissue Res 2:127–136PubMedCrossRefGoogle Scholar
  29. 29.
    Deshmukh K, Kline WG (1976) Characterization of collagen and its precursors synthesized by rabbit articular cartilage cells in various culture systems. Eur J Biochem 69:117–123CrossRefPubMedGoogle Scholar
  30. 30.
    Norby DP, Malemud CJ, Sokoloff L (1977) Differences in the collagen types synthesized by lapine articular chondrocytes in spinner and monolayer culture. Arthritis Rheum 20:709–716PubMedGoogle Scholar
  31. 31.
    Benya PD, Shaffer JD (1982) Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30:215–224CrossRefPubMedGoogle Scholar
  32. 32.
    Hsu TC, Benirschke K (1967) The atlas of mammalian chromosomes, vol 1. Springer-Verlag, New YorkGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1983

Authors and Affiliations

  • Jack M. Lipman
    • 1
  • Cahir A. McDevitt
    • 1
  • Leon Sokoloff
    • 1
  1. 1.Department of PathologyState University of New York at Stony BrookStony BrookUSA

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