Local induction of heat shock protein 70 (Hsp70) by proteasome inhibition confers chondroprotection during surgically induced osteoarthritis in the rat knee.
OBJECTIVE
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).


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 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.


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.
Etienne
Stéphanie
S
Physiopathologie et Pharmacologie Articulaires, UMR 7561 CNRS - Nacny Universite, Vandoeuvre les Nancy, France.
Gaborit
Nadège
N
Henrionnet
Christel
C
Pinzano
Astrid
A
Galois
Laurent
L
Netter
Patrick
P
Gillet
Pierre
P
Grossin
Laurent
L
D000818:Animals; D001178:Arthroplasty / Q000009:adverse effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007976:Leupeptins / Q000008:administration & dosage*; D008297:Male; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D061988:Proteasome Inhibitors; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D015853:Cysteine Proteinase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007976:Leupeptins; D061988:Proteasome Inhibitors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde