Induction of heat shock protein 70 (Hsp70) by proteasome inhibitor MG 132 protects articular chondrocytes from cellular death in vitro and in vivo.
The aim of this work was to determine whether Hsp70 overexpression via proteasome inhibitor MG132 was able to protect chondrocytes towards mono-iodoacetate (MIA) cytotoxicity both in vitro and in vivo. In vitro, overexpression of Hsp70 via MG132 was significantly able to protect chondrocytes from MIA toxicity (MTT/LDH analyses). Hsp70 essentially mediated this chondroprotective effect as demonstrated by antisense strategy. In vivo, chondrocytic overexpression of Hsp70, after a preventive intra-articular injection of MG132 in rat knee, was sufficient to decrease the severity of OA-induced MIA lesions, as demonstrated histologically and biochemically. In conclusion, intracellular overexpression of Hsp70, through proteasome inhibition, could be an interesting tool in protecting chondrocytes from cellular injuries, either necrotic or apoptotic in nature, and thus might be a novel chondroprotective modality in rat experimental OA.
UMR 7561 CNRS -- Université Nancy I, Faculté de Médicine de Nancy, Vandoeuvre, France.
Laurent
L
Grossin
Stéphanie
S
Etienne
Nadège
N
Gaborit
Astrid
A
Pinzano
Christel
C
Cournil-Henrionnet
Catherine
C
Gerard
Elisabeth
E
Payan
Patrick
P
Netter
Bernard
B
Terlain
Pierre
P
Gillet
D000818:Animals; D002358:Cartilage, Articular; D016923:Cell Death; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018840:HSP70 Heat-Shock Proteins; D007976:Leupeptins; D016376:Oligonucleotides, Antisense; D011480:Protease Inhibitors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde