Regulatory mechanism of transforming growth factor beta receptor type II degradation by interleukin-1 in primary chondrocytes

Catherine Baugé (1, 2) , Nicolas Girard (2, 1) , Sylvain Leclercq (3, 2, 1) , Philippe Galéra (1) , Karim Boumédiene (2, 1)

1 BioConnecT - Microenvironnement et Pathologies du Cartilage
2 NU - Normandie Université
3 Département de chirurgie orthopédique [Hôpital privé Saint Martin Caen]

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.

Domaines: Rhumatologie et système ostéo-articulaire; Biochimie, Biologie Moléculaire; Biologie cellulaire

Catherine Baugé, Nicolas Girard, Sylvain Leclercq, Philippe Galéra, Karim Boumédiene. Regulatory mechanism of transforming growth factor beta receptor type II degradation by interleukin-1 in primary chondrocytes. BBA - Biochimica et Biophysica Acta, 2012, 1823 (5), pp.983-6. ⟨10.1016/j.bbamcr.2012.02.017⟩. ⟨hal-01149560⟩