Local induction of heat shock protein 70 (Hsp70) by proteasome inhibition confers chondroprotection during surgically induced osteoarthritis in the rat knee
Issue title: Bioengineering and Biotherapies, September 2007, Nancy
Affiliations: Physiopathologie et Pharmacologie Articulaires, UMR 7561 CNRS – Nancy Université, Faculté De Médecine, UMR 7561 CNRS – Nancy Université, Vandœuvre lès Nancy, France
Note: [] Equal contribution to this work.
Note: [] Address for correspondence: Pierre Gillet, Physiopathologie et Pharmacologie Articulaires, Faculté De Médecine, UMR 7561 CNRS – Nancy Université, Avenue De La Forêt De Haye Bp 184, F 54505 Vandœuvre lès Nancy, France. E-mail: P.Gillet@Chu-Nancy.Fr.
Abstract: Aim: to determine if chondrocytic Hsp70 induction, via intra-articular injections of a reversible proteasome inhibitor (MG132), can protect articular chondrocytes from cellular death in experimental rat OA knee induced surgically by anterior cruciate ligament transection (ACLT). Materials and methods: ACLT was performed on D0. Histological lesions in naive (sham) controls (ACLT+saline) and treated (ACLT+MG132) rats were assessed according to Mankin's score. Repeated intra-articular injections (1.5 μM MG132 or saline were performed on D1, D7, D14 and D21. Rats were sacrificed sequentially on D7, D14 and D28. Detection of active caspase-3 and protein expression of Hsp70 was also determined on D7, D14 and D28 by immunostaining methods. Results: MG132 significantly reduced OA lesions on D28 in the MG132 treated group. The expression of Hsp70 increased 11-fold in the MG132-treated group versus 2-3-fold in ACLT-control rats on D28. Concomitantly, cells expressing caspase-3 increased 4-fold in ACLT model and decreased 2-fold with MG132 treatment. Conclusions: Intra-articular induction of Hsp70 by MG132 could be a safe and interesting tool in chondrocytes protection from cellular injuries and thus might be a novel chondroprotective modality in rat OA.
