Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis.
Osteoarthritis is characterized by a gradual degradation of extracellular matrix, resulting from an excess of chondrocyte cell death, mainly due to an increase in apoptotis. Recent studies have revealed the essential role of HSP70 in protecting cells from stressful stimuli. Therefore, overexpressing HSP70 in chondrocytes could represent a good strategy to prevent extracellular matrix destruction. To this end, we have developed a vector carrying HSP70/GFP, and transduced chondrocytes were thus more resistant to cell death induced by mono-iodoacetate (MIA). To overcome the barrier-effect of matrix, we investigated the efficacy of plasmid delivery by electroporation (EP) in rat patellar cartilage. Two days after EP, 50% of patellar chondrocytes were HSP/GFP+. After 3 months, long-term expression of transgene was only depicted in the deep layer (20-30% positive cells). HSP70 overexpression inhibited the natural endochondral ossification in the deep layer, thus leading to a lesser decrease in chondrocyte distribution. Moreover, overexpression of HSP70, after a preventive EP transfer in rat patella, was sufficient to decrease the severity of osteoarthritis-induced lesions, as demonstrated histologically and biochemically. In conclusion, intracellular overexpression of HSP70, through EP delivery, could protect chondrocytes from cellular injuries and thus might be a novel chondroprotective modality in rat OA.
Grossin
Laurent
L
Unité Mixte de Recherches 7561, Centre National de la Recherche Scientifique-Université Henri Poincaré Nancy 1, Faculté de Médecine, Vandoeuvre lès Nancy, France.
Cournil-Henrionnet
Christel
C
Pinzano
Astrid
A
Gaborit
Nadège
N
Dumas
Dominique
D
Etienne
Stéphanie
S
Stoltz
Jean François
JF
Terlain
Bernard
B
Netter
Patrick
P
Mir
Lluis M
LM
Gillet
Pierre
P
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D019610:Cytoprotection; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006614:Hindlimb; D007596:Joints / Q000473:pathology; D008297:Male; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
D018840:HSP70 Heat-Shock Proteins