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Titolo:
Gene transfer of p53 to arthritic joints stimulates synovial apoptosis andinhibits inflammation
Autore:
Yao, QP; Wang, SJ; Glorioso, JC; Evans, CH; Robbins, PD; Ghivizzani, SC; Oligino, TJ;
Indirizzi:
Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15219 USA Univ Pittsburgh Pittsburgh PA USA 15219 Biochem, Pittsburgh, PA 15219 USA Harvard Univ, Sch Med, Ctr Mol Orthopaed, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 Ctr Mol Orthopaed, Boston, MA 02115 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 3, anno: 2001,
pagine: 901 - 910
SICI:
1525-0016(200106)3:6<901:GTOPTA>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR GENE; FIBROBLAST-LIKE SYNOVIOCYTES; RAPID COLORIMETRIC ASSAY; RHEUMATOID-ARTHRITIS; ADENOVIRUS VECTORS; SOMATIC MUTATIONS; GENOTOXIC STRESS; EXPRESSION; GROWTH; TISSUE;
Keywords:
arthritis; p53; apoptosis; gene therapy; adenovirus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Oligino, TJ Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Suite 206,300 Technol Dr, Pittsburgh, PA 15219 USA Univ Pittsburgh Suite 206,300 Technol Dr Pittsburgh PA USA 15219
Citazione:
Q.P. Yao et al., "Gene transfer of p53 to arthritic joints stimulates synovial apoptosis andinhibits inflammation", MOL THER, 3(6), 2001, pp. 901-910

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects joints. During the pathogenesis of rheumatoid arthritis, the synovial lining becomes dramatically thickened and hyperplastic. This highly aggressive tissue invades and destroys articular cartilage and bone. Several lines of evidence suggest that the proliferation of the synovial tissue may be due todisruption in the control of the cell cycle or apoptotic pathways. In particular, mutations in the tumor suppressor protein p53 have been found in synovial tissue from RA joints. We have examined the effects of overexpression of p53 by adenoviral infection in synovial cells in culture and in synovial tissue in vivo in a rabbit model of arthritis. Here we demonstrate that p53 overexpression resulted in significant apoptosis in human and rabbit synovial cells in culture. Furthermore, intraarticular injection of Ad-p53 resulted in extensive and rapid induction of synovial apoptosis in the rabbitknee without affecting cartilage metabolism. Interestingly, a significant reduction in the leukocytic infiltrate was observed within 24 h postinfection of Ad.p53. These results suggest that intraarticular gene transfer of p53 is able to induce synovial apoptosis as well as reduce inflammation and thus may be useful clinically for the treatment of RA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 23:41:45