RGD Reference Report - Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis. - Rat Genome Database

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Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis.

Authors: Grossin, L  Cournil-Henrionnet, C  Pinzano, A  Gaborit, N  Dumas, D  Etienne, S  Stoltz, JF  Terlain, B  Netter, P  Mir, LM  Gillet, P 
Citation: Grossin L, etal., FASEB J. 2006 Jan;20(1):65-75.
RGD ID: 10402538
Pubmed: PMID:16394269   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.04-2889com   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Osteoarthritis, Experimental treatmentISOHspa1a (Rattus norvegicus)10402538; 10402538 RGD 
Osteoarthritis, Experimental treatmentIMP 10402538 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IMP 10402538 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa1a  (heat shock protein family A (Hsp70) member 1A)

Genes (Mus musculus)
Hspa1a  (heat shock protein 1A)

Genes (Homo sapiens)
HSPA1A  (heat shock protein family A (Hsp70) member 1A)


Additional Information