Le TGFβI dans la physiopathologie de l'arthrose et son rôle dans l'effet thérapeutique des cellules souches mésenchymateuses

Abstract : Osteoarthritis (OA) is the most common form of joint diseases without curative treatments. The disease is mainly characterized by the degradation of articular cartilage which is associated with other pathological changes in joint tissues. In this context, mesenchymal stem cells (MSC) have demonstrated a therapeutic effect. In order to identify new mediators involved in articular homeostasis, we analyzed MSC secretome, focusing on the transforming growth factor β (TGFβ) members, a central pathway dysregulated in OA.This approach allows us to identify the TGFβ induced protein (TGFβI or βIGH3). In the present study, we evaluated its role in the differentiation of MSC and compared its expression in articular tissues from OA patients and healthy donors.We highlight the importance of TGFβI in the regulation of differentiation of MSC towards bone and cartilage. We also demonstrate its dysregulation at both transcript and protein level in cartilage, bone and MSC from OA patients. We then evaluated its role in the therapeutic effect of MSC in vitro and in vivo and demonstrated that its decreased expression in MSC is associated with a loss of their therapeutic effect in OA models. The chondroprotective effect of TGFβI is associated with an inhibition of bone remodeling and calcification of soft articular tissues.Together, our results highlight the importance of the TGFβ pathway, and specially of TGFβI regulation, in joint homeostasis. Moreover, our work demonstrates its role in the therapeutic effect of MSC, suggesting that its dysregulation in OA MSC could lead to a decreased regenerative potential.
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Submitted on : Tuesday, July 10, 2018 - 5:06:19 PM
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Maxime Ruiz. Le TGFβI dans la physiopathologie de l'arthrose et son rôle dans l'effet thérapeutique des cellules souches mésenchymateuses. Rhumatologie et système ostéo-articulaire. Université Montpellier, 2018. Français. ⟨NNT : 2018MONTT008⟩. ⟨tel-01834605⟩

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