Etude des potentialités des agonistes des récepteurs activés par les proliférateurs de péroxysomes (PPAR) sur les réponses chondrocytaires induites par le Transforming Growth Factor Beta (TGF-[bêta]

Abstract : When considering the bipotential effects of TGF-[bêta]1 and the antifibrotic effect associated with PPAR activation in many organs, we investigated the ability of synthetic PPAR agonists of the three isotypes ([alpha], [beta/delta] and [gamma]) to affect TGF-[beta]1-induced metabolism responses in rat chondrocytes. ln our report, we choose alginate as the optimal culture system. ln addition, using a panel of PPAR target genes, we demonstrate that Wy14643, GW501516 and rosiglitazone induced preferentially [alpha]-, [beta/delta]- and [gamma]-dependent responses respectively, while pioglitazone induced "[gamma] > [alpha]" responses. Moreover, the stimulating effect of TGF-[beta]1 on proteoglycans or collagens synthesis is reduced dramatically by all PPAR agonists via early and/or tardive inhibitions of Smads, ERK1/2 and/or PGE2 pathways. This could suggest that PPAR agonists inhibit crucial activities and regulate extracellular matrix (ECM) turnover biosynthesis by restoring MMPs activities. These regulations were found to be dependant of the selectivity profile of each agonist in rat chondrocytes. Taken all together, our data demonstrate that PPAR agonists reduce TGF-[beta]1-induced responses in rat chondrocytes and may favour an altered repair capacity of cartilage in response to some articular joint growth factors, like TGF-[beta]. Due to the complexity of the involved mechanisms related to the physiopathological role of TGF-[beta]1 and to the lack of chondroprotection provided by PPAR agonists in cartilage, further studies are required.
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Theses
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http://docnum.univ-lorraine.fr/prive/SCD_T_2006_0252_POLENI.pdf
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https://hal.univ-lorraine.fr/tel-01747007
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Submitted on : Thursday, March 29, 2018 - 10:49:24 AM
Last modification on : Monday, April 16, 2018 - 10:40:58 AM

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Paul-Emile Poleni. Etude des potentialités des agonistes des récepteurs activés par les proliférateurs de péroxysomes (PPAR) sur les réponses chondrocytaires induites par le Transforming Growth Factor Beta (TGF-[bêta]. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10252⟩. ⟨tel-01747007⟩

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