Article

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

L'Oréal, Centre de Recherche Charles Zviak, 92583 Clichy Cedex, France.
Rheumatology International (Impact Factor: 1.63). 04/2005; 25(2):118-24. DOI: 10.1007/s00296-003-0409-x
Source: PubMed

ABSTRACT Osteoarthritis (OA) is characterized by erosion of cartilage and formation of osteophytes. Since transforming growth factor beta (TGF-beta) is known to be involved in chondrogenesis and osteogenesis, we studied by immunochemistry the expression of TGF-beta 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.
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-beta(1-3) and TGF-beta receptors I and II.
TGF-beta1 expression was shown to be depressed in strongly degraded cartilage, compared to normal and slightly altered areas. TGF-beta2 was barely detectable in all samples studied. In osteophytes, a marked overexpression of TGF-beta1 and -beta3 was observed. An important decrease in TGF-beta receptor II was found in fibrillated cartilage areas.
The three major isoforms of TGF-beta are expressed in human OA cartilage, albeit the TGF-beta2 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-beta1 production and marked downregulation of receptor II in fibrillated cartilage may lead to reduced chondrocyte responsiveness to TGF-beta and contribute to the irreversibility of the disease. Overexpression of TGF-beta1 and -beta3 in osteophytes suggests that the two isoforms are involved in the formation of these structures.

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    • "It induces its signal through activation of type I (TßRI) and type II (TßRII) receptors. These receptors play a major role in osteoarthritis (OA) [2] [3]. Their expression as well as their membrane compartmentalization regulates TGFß1 signaling [4] [5] [6]. "
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    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 05/2012; 1823(5):983. DOI:10.1016/j.bbamcr.2012.02.017. · 5.30 Impact Factor
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    • "It induces its signal through activation of type I (TßRI) and type II (TßRII) receptors. These receptors play a major role in osteoarthritis (OA) [2] [3]. Their expression as well as their membrane compartmentalization regulates TGFß1 signaling [4] [5] [6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-1β (IL-1β), a key-cytokine in osteoarthritis, impairs TGFβ signaling through TβRII down-regulation by increasing its degradation. Here, we investigated the molecular mechanism that controls TßRII fate in IL-1ß treated cells. Chondrocytes were treated with IL-1ß in the presence of different inhibitors. TßRII and Cav-1 expression were assayed by Western blot and RT-PCR. We showed that IL-1ß-induced degradation of TßRII is dependent on proteasome and on its internalization in caveolae. In addition, IL-1ß enhances Cav-1 expression, a major constituent of lipid raft. In conclusion, we enlighten a new mechanism by which IL-1ß antagonizes TGFß pathway and propose a model of TßRII turnover regulation upon IL-1ß treatment.
    Biochimica et Biophysica Acta 03/2012; 1823(5):983-6. DOI:10.1016/j.bbamcr.2012.02.017 · 4.66 Impact Factor
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    • "Degradation of cartilage extracellular matrix (ECM) by proinflammatory cytokine-stimulated matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS or A Dystrophin And Metalloproteinase with ThromboSpondin motif) [1] [2] is observed in inflammatory rheumatoid arthritis (RA) and aging-associated osteoarthritis (OA), the most prominent forms of arthritis in clinic [3] [4]. Cartilage from older patients has limited capacity to regenerate due to reduced transforming growth factor beta (TGF-β) and its type II receptor, and resulting chondrocyte hyporesponsiveness [5]. TGF-β super-family members stimulate chondrogenesis during development and maintain cartilage integrity in adults [6] [7]. "
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