Étude de la contribution des récepteurs activés par les proliférateurs de peroxysomes en physiopathologie articulaire

Abstract : Peroxisome proliferator-activated receptors (PPARs) are transcription factors implicated in lipid metabolism and glucose tolerance. Once activated by specific agonists, PPARs control inflammation associated with numerous diseases, notably Rheumatoid arthritis. The first study presented here aim to compare the anti-arthritic potency of two high-affinity synthetic agonists for PPAR[alpha] and PPAR[gamma] in an experimental model. Then we focused on the effect of pioglitazone, a high-affinity synthetic agonists for PPAR[gamma], and demonstrated that a per os treatment with this agonist not only reduced experimental arthritis but also inhibited partly inflammation-related bone loss by preserving bone microarchitecture. We pointed out that PPAR[gamma], on one hand, regulated local and systemic expression of interleukine-17 (IL-17) and RANKL and on the other hand, inhibited expression of transcription factor ROR[gamma]t, a main regulator of IL-17/Th17 pathway. Study of mice deficient for PPAR[gamma] confirmed its major role in the development of the arthritic process since these mice developed spontaneously arthritis. Of interest arthritis in these mice is associated with increased number of synovial mast cells able to produce IL-17 and their own differenciation factor, the SCF. Finally, we discussed the possible link between inflammatory arthritis and mastocytosis in a case report of a patient suffering from rheumatoid arthritis concomitant to systemic mastocytosis
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Meriem Tibari-Koufany. Étude de la contribution des récepteurs activés par les proliférateurs de peroxysomes en physiopathologie articulaire. Médecine humaine et pathologie. Université de Lorraine, 2015. Français. ⟨NNT : 2015LORR0230⟩. ⟨tel-01754490⟩

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