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Immunohistochemical analysis of transforming growth factor beta isoforms and their receptors in human cartilage from normal and osteoarthritic femoral heads

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Abstract

Objective

Osteoarthritis (OA) is characterized by erosion of cartilage and formation of osteophytes. Since transforming growth factor beta (TGF-β) is known to be involved in chondrogenesis and osteogenesis, we studied by immunochemistry the expression of TGF-β isoform types 1, 2, and 3 and their receptor types I and II in slightly and strongly altered areas of human OA cartilage and in osteophytes.

Methods

Specimens were collected from femoral heads at the time of hip arthroplasty, selecting osteophytic regions and areas of slight or severe degradation according to the Mankin score. Cryostat sections were prepared and submitted to immunohistochemistry using appropriate antibodies to TGF-β1–3 and TGF-β receptors I and II.

Results

TGF-β1 expression was shown to be depressed in strongly degraded cartilage, compared to normal and slightly altered areas. TGF-β2 was barely detectable in all samples studied. In osteophytes, a marked overexpression of TGF-β1 and -β3 was observed. An important decrease in TGF-β receptor II was found in fibrillated cartilage areas.

Conclusions

The three major isoforms of TGF-β are expressed in human OA cartilage, albeit the TGF-β2 level is very low. Their expression patterns and the ratio of receptors I and II varies according to the degree of OA severity. The decrease in TGF-β1 production and marked downregulation of receptor II in fibrillated cartilage may lead to reduced chondrocyte responsiveness to TGF-β and contribute to the irreversibility of the disease. Overexpression of TGF-β1 and -β3 in osteophytes suggests that the two isoforms are involved in the formation of these structures.

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Acknowledgements

We thank Prof. Vielpeau (Department of Orthopedic Surgery) for providing samples of femoral heads and Prof. Rousselot (Department of Anatomicopathology) for providing facilities for histological analysis. This study was supported by grants from the University of Caen and the Regional Council of Normandy.

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Authors and Affiliations

  1. L’Oréal, Centre de Recherche Charles Zviak, 92583, Clichy Cedex, France

    M.-P. Verdier & S. Seité

  2. Centre Anticancéreux F. Baclesse, 14000, Caen, France

    K. Guntzer

  3. Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, Avenue de la Côte de Nacre, 14032, Caen Cedex, France

    J.-P. Pujol & K. Boumédiène

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  1. M.-P. Verdier
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  2. S. Seité
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  3. K. Guntzer
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  4. J.-P. Pujol
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  5. K. Boumédiène
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Correspondence to J.-P. Pujol.

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Verdier, MP., Seité, S., Guntzer, K. et al. Immunohistochemical analysis of transforming growth factor beta isoforms and their receptors in human cartilage from normal and osteoarthritic femoral heads. Rheumatol Int 25, 118–124 (2005). https://doi.org/10.1007/s00296-003-0409-x

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  • DOI: https://doi.org/10.1007/s00296-003-0409-x

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