Contribution du gène "Ank" dans la balance PPi/Pi et dans le maintien du phénotype du chondrocyte articulaire

Abstract : Articular chondrocalcinosis (CCA) are microcrystalline arthtopathies characterized by the presence of calcium pyrophosphate dihydrate crystals (CPPD) in the cartilage. There are 3 forms of CCA, including the familal forms, dependent upon an autosomal dominant transmission mechanism, the sporadic forms, whose probability of occurrence increases with ageing, and the metabolic forms, secondary to other pathologies like hyperparathyroidism. The Ank gene encodes a transporter which exports inorganic pyrophosphate (PPi) outside the cells. A link is well established between mutations in the coding sequence of the Ank gene and the familial forms of CCA. We studied, on one hand, the contribution of the Ank gene in the production of PPi by articular chondrocytes stimulated with transforming growth factor-[bêta]1 (TGF-[bêta]1), since the sensitivity of chondrocytes to this growth factor increases with ageing. On the other hand, since CPPD are often associated with osteoarthritis (OA), and since Ank expression levels influences the chondrogenesis, we elucidated the possible implication of Ank in the loss of the articular chondrocytes phenotype observed during OA. Finally, we analyzed the role of calcium on the TGF-[bêta]1 effects on ePPi production, hypercalcaemia being often found during hyperparathyroidism. This work allowed demonstrating, on one hand, the predominant role of ANK in the situations of chondrocytic hypersensitivity to TGF-[bêta]1. On the other hand, the PPi exported by ANK influences the expression of articular chondrocytic markers. Finally, calcium plays a crucial role in the inducer effects of TGF-[bêta]1 in the production of PPi.
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Frédéric Cailotto. Contribution du gène "Ank" dans la balance PPi/Pi et dans le maintien du phénotype du chondrocyte articulaire. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10114⟩. ⟨tel-01748300⟩

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