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).
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 muM 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.
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.
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.