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Immunohistological study on collagen in cartilage-bone metamorphosis and degenerative osteoarthrosis

Immunhistologische Untersuchungen an Kollagen bei der Knorpel-, Knochenumwandlung und in der degenerativen Osteoarthrose

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Zusammenfassung

Unter Verwendung von spezifischen Antikörpern ist es möglich, mit Hilfe immunhistologischer Methoden die Verteilung der verschiedenen Kollagentypen und auch die Kollagensynthese einzelner Zellen zu verfolgen. Diese Methode wurde angewendet, um die Kollagensynthese von Chondrocyten im normalen Gelenkknorpel, Epiphysenknorpel der Wachstumsplatte, osteoarthrotischen Gelenkknorpel, sowie unter in vitro Kulturbedingungen zu verfolgen. Während im normalen Knorpel nur Typ II Kollagen synthetisiert wird, wurde festgestellt, daß die hypertrophierenden großen Chondrocyten an der Basis des Säulenknorpels auf die Synthese des Typ I Kollagens umschalten. Ähnliches gilt auch für die arthrotischen Zellen des Gelenkknorpels. Hier führt die Degeneration zu einer Umschaltung der Kollagensynthese von Typ II auf Typ I Kollagen. Dieses Phänomen kann auch in vitro nachvollzogen werden. In Suspensionskulturen, in denen Chondrocyten in Aggregaten eine knorpelähnliche Matrix aufzubauen vermögen, vollzieht sich der Umschaltungsprozeß langsamer als in Monolayerkulturen.

Diese Beobachtungen zeigen, daß Chondrocyten zur Aufrechterhaltung ihrer Typ II Kollagensynthese eine spezielle Zell-Matrix-Wechselwirkung benötigen. Wird durch eine Veränderung der Knorpelmatrix (z.B. bei dem Degenerationsprozeß der Osteoarthrose) diese Wechselbeziehung gestört, kommt es zu einer Neuorientierung der Kollagensynthese und — in deren Folge — zur Umschaltung auf Typ I Kollagen.

Summary

Synthesis of collagen by chondrocytes was studied by immunofluorescence using antibodies specific for type I, II and III collagen. The following tissues and culture conditions were chosen for this immunohistological study: normal articular cartilage, epiphyseal growth cartilage, cartilage undergoing osteoarthrotic degeneration, suspension culture and monolayer culture. While type II collagen is the unique collagen all over hyaline cartilage, type I collagen is produced by hypertrophic chondrocytes in the growth plate. In addition, chondrocytes in osteoarthrotic areas of articular cartilage synthesize type I collagen. Under in vitro culture conditions, chondrocytes initially produce type II collagen and synthesize later on type I collagen. The change of synthesis from type II to type I collagen is more rapid in monolayer than in suspension culture. It is concluded that the presence of matrix compounds and the cellmatrix interaction as well are necessary to maintain synthesis of type II collagen in chondrocytes. Alterations in the cell-matrix interactions are shown to occur in the hypertrophic zone of the epiphyseal growth plate, in cartilage undergoing osteoarthrotic degeneration as well as in chondrocytes grown in culture. Thus, change in the control of gene activity may subsequently lead to change in collagen synthesis. It is possible that the synthesis of type I collagen, which cannot fulfil the physiological function of a structural element in cartilageneous tissue, is a crucial factor in the process of osteoarthrosis.

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Abbreviations

EDTA:

Ethylendiaminetetraacetate

FITC:

Fluoresceine isothiocyanate

References

  1. Becker, U., Nowack, H., Gay, S., Timpl, R.: Production and specificity of antibodies against the aminoterminal region in type III collagen. Immunology31, in press

  2. Chung, E., Miller, E.J.: Collagen polymorphism: characterization of molecules with the chain composition (α1(III))3 in human tissues. Science183, 1200 (1975)

    Google Scholar 

  3. Dehm, P., Prockop, D.J.: Biosynthesis of cartilage procollagen. Europ. J. Biochem.35, 159 (1973)

    PubMed  Google Scholar 

  4. Deshmukh, K., Nimni, M.: Effects of lysosomal enzymes on the type of collagen synthesized by bovine articular cartilage. Biochem. biophys. Res. Commun.53, 424 (1973)

    PubMed  Google Scholar 

  5. Epstein, E.H., Jr.: (α1(III))3 human skin collagen. J. biol. Chem.249, 3225 (1974)

    PubMed  Google Scholar 

  6. Freeman, M.: The fatigue of cartilage in the pathogenesis of osteoarthrosis. Acta orthop. scand.46, 323 (1975)

    PubMed  Google Scholar 

  7. Freeman, M., Meachim, G.: Ageing, regeneration and remodelling of articular cartilage. In: Adult Articular Cartilage, ed. M.A.R. Freeman, Sir Isaac Pitman and Sons, 287 (1973)

  8. Furthmayr, H., Timpl, R.: Immunochemistry of collagens and procollagens. Int. Review of Connective Tissue Research7, 61 (1976)

    Google Scholar 

  9. Gay, S., Balleisen, L., Remberger, K., Fietzek, P.P., Adelmann, B.C., Kühn, K.: Immunohistochemical evidence for the presence of collagen type III in human arterial walls, arterial thrombi and leukocytes, incubated with collagen in vitro. Klin. Wschr.53, 899 (1975a)

    PubMed  Google Scholar 

  10. Gay, S., Fietzek, P.P., Remberger, K., Eder, M., Kühn, K.: Liver cirrhosis: Immunofluorescence and biochemical studies demonstrate two types of collagen. Klin. Wschr.53, 205 (1975b)

    PubMed  Google Scholar 

  11. Gay, S., Remberger, K., Müller, P.K., Lemmen, C., Adelmann, B.C.: Immunfluoreszenzmikroskopische Differenzierung von Kollagentyp I, II and III mit hochgereinigten Antikörpern im alternden Bindegewebe. Verh. dtsch. Ges. Path.59, 272 (1975c)

    Google Scholar 

  12. Gay, S., Müller, P.K., Meigel, W.N., Kühn, K.: Polymorphie des Kollagens. Neue Aspekte für Struktur und Funktion des Bindegewebes. Hautarzt27, in press. (1976a)

  13. Gay, S., Martin, G.R., Müller, P.K., Timpl, R., Kühn, K.: Simultaneous synthesis of type I and type III collagens by fibroblasts in culture. Proc. nat. Acad. Sci. (Wash.) (1976b) in press

  14. Hahn, E., Timpl, R., Müller, E.J.: The production of specific antibodies to native collagen with the chain composition (α1(I))3, (α1(II))3 and (α1(I)α2). J. Immunol.113, 421 (1974)

    PubMed  Google Scholar 

  15. Holtzer, H., Abbot, J.: The stability of the differentiated state. Ed.: Beerman, W., Reinert, J. and Ursprung, H. Springer, Berlin, p. 1 (1968)

  16. Landells, J.W.: The reactions of injured human articular cartilage. J. Bone Jt. Surg.39, 548 (1957)

    Google Scholar 

  17. Layman, D.L., Sokoloff, L., Miller, E.J.: Collagen synthesis by articular cartilage in monolayer culture. Exp. Cell Res.73, 107 (1972)

    PubMed  Google Scholar 

  18. Levitt, D., Dorfman, A.: Concepts and mechanism of cartilage differentiation. Develop. Biol.8, 103 (1974)

    Google Scholar 

  19. Mayne, R., Vail, M., Miller, E.J.: Analysis of changes in collagen biosynthesis that occur when chick chondrocytes are grown in 5-bromo-2′-deoxyuridine. Proc. nat. Acad. Sci. (Wash.)72, 4511 (1975)

    PubMed  Google Scholar 

  20. Meachim, G., Collins, D.H.: Cell counts of normal and osteoarthritic articular cartilage in relation to the uptake of sulfate (35SO4) in vitro. Ann. rheum. Dis.21, 45 (1962)

    PubMed  Google Scholar 

  21. Meachim, G., Fergie, I.: Morphological patterns of articular cartilage fibrillation. J. Pathol.115, 231 (1975)

    PubMed  Google Scholar 

  22. Müller, P.K., Jamhawi, O.: The biosynthesis of a precursor of cartilage collagen by embryonic chicken sterna in the presence of α,α′-dipyridyl. Biochim. biophys. Acta (Amst.)365, 158 (1974)

    PubMed  Google Scholar 

  23. Müller, P.K., Lemmen, C., Gay, S., Meigel, W.N.: Disturbance in the regulation of the type of collagen synthesized in a form of osteogenesis imperfecta. Europ. J. Biochem.59, 97 (1975a)

    PubMed  Google Scholar 

  24. Müller, P.K., Lemmen, C., Gay, S., von der Mark, K., Kühn, K.: Biosynthesis of collagen by chondrocytes in vitro. In: Extracellular Matrix Influences on Gene Expression. Academic Press, Inc., New York, San Francisco, p. 293 (1975b)

    Google Scholar 

  25. Nimni, M.: Collagen, its structure and function on normal and pathological connective tissue. Sem. Arthr. Rheum.4, 95 (1974)

    Google Scholar 

  26. Nimni, M., Deshmukh, K.: Differences in collagen metabolism between normal and osteoarthrotic human cartilage. Science181, 751 (1973)

    PubMed  Google Scholar 

  27. Nowack, H., Gay, S., Wick, G., Becker, U., Timpl, R.: Preparation and use in immunohistology of antibodies specific for type I and type III collagen and procollagen. J. Immunol. Method., submitted

  28. Penttinen, R.P., Lichtenstein, J.R., Martin, G.R., McKusick, V.A.: Abnormal metabolism in cultured cells in osteogenesis imperfecta. Proc. nat. Acad. Sci. (Wash.)72, 586 (1975)

    PubMed  Google Scholar 

  29. Pope, F.M., Martin, G.R., Lichtenstein, J.R., Penttinen, R., Gerson, B., Rowe, D.W., McKusick, V.A.: Patient with Ehlers-Danlos Syndrome Type IV lack type VII collagen. Proc. nat. Acad. Sci. (Wash.)72, 1314 (1975)

    PubMed  Google Scholar 

  30. Schiltz, J.R., Mayne, R., Holtzer, H.: The synthesis of collagen and glycosaminoglycans by dedifferentiated chondroblasts, in culture. Differentiation1, 97 (1973)

    Google Scholar 

  31. von der Mark, H., von der Mark, K., Gay, S.: Study of differential collagen synthesis during development of the chick embryo by immunofluorescence: I. Preparation of collagen type I and type II specific antibodies and their application to early stages of chick embryo. Develop. Biol.48, 237 (1976)

    PubMed  Google Scholar 

  32. Wick, G., Furthmay, H., Timpl, R.: Purified antibodies to collagen: an immunofluorescence reaction with tissue collagen. Int. Arch. Allergy48, 664 (1975)

    PubMed  Google Scholar 

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This investigation was supported by grants of the Deutsche Forschungsgemeinschaft, Mu 378/4, Re 388/1 and SFB 51

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Gay, S., Müller, P.K., Lemmen, C. et al. Immunohistological study on collagen in cartilage-bone metamorphosis and degenerative osteoarthrosis. Klin Wochenschr 54, 969–976 (1976). https://doi.org/10.1007/BF01468947

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