Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation

Qingping Yao, Sujing Wang, Joseph C. Glorioso, Christopher H Evans, Paul D. Robbins, Steven C. Ghivizzani, Thomas J. Oligino

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 to disruption 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 rabbit knee 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.

Original languageEnglish (US)
Pages (from-to)901-910
Number of pages10
JournalMolecular Therapy
Volume3
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

p53 Genes
Arthritis
Rheumatoid Arthritis
Joints
Apoptosis
Inflammation
Rabbits
Cell Culture Techniques
Tumor Suppressor Protein p53
Intra-Articular Injections
Articular Cartilage
Cell Cycle Checkpoints
Autoimmune Diseases
Cartilage
Knee
Bone and Bones
Mutation
Infection
Therapeutics

Keywords

  • Adenovirus
  • Apoptosis
  • Arthritis
  • Gene therapy
  • p53

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Yao, Q., Wang, S., Glorioso, J. C., Evans, C. H., Robbins, P. D., Ghivizzani, S. C., & Oligino, T. J. (2001). Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. Molecular Therapy, 3(6), 901-910. https://doi.org/10.1006/mthe.2001.0343

Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. / Yao, Qingping; Wang, Sujing; Glorioso, Joseph C.; Evans, Christopher H; Robbins, Paul D.; Ghivizzani, Steven C.; Oligino, Thomas J.

In: Molecular Therapy, Vol. 3, No. 6, 2001, p. 901-910.

Research output: Contribution to journalArticle

Yao, Q, Wang, S, Glorioso, JC, Evans, CH, Robbins, PD, Ghivizzani, SC & Oligino, TJ 2001, 'Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation', Molecular Therapy, vol. 3, no. 6, pp. 901-910. https://doi.org/10.1006/mthe.2001.0343
Yao, Qingping ; Wang, Sujing ; Glorioso, Joseph C. ; Evans, Christopher H ; Robbins, Paul D. ; Ghivizzani, Steven C. ; Oligino, Thomas J. / Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. In: Molecular Therapy. 2001 ; Vol. 3, No. 6. pp. 901-910.
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