Inhibition of rheumatoid synovial fibroblast proliferation by antisense oligonucleotides targeting proliferating cell nuclear antigen messenger RNA

Yoshitaka Morita, Naoki Kashihara, Masahiro Yamamura, Hideyuki Okamoto, Seishi Harada, Yohei Maeshima, Kazunori Okamoto, Hirofumi Makino

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective. To evaluate the feasibility of antisense oligonucleotides as therapeutic agents to inhibit synovial cell growth in rheumatoid arthritis (RA). Methods. Fibroblast-like cells established from RA synovium were stimulated with interleukin-lβ (IL1β) and treated with antisense or sense oligonucleotides targeting proliferating cell nuclear antigen (PCNA) messenger RNA (mRNA). Proliferation of these cells was determined by 3H- thymidine incorporation. Effects of antiseuse oligonudeotides on the expression of mRNA and protein were evaluated by reverse transcriptase- polymerase chain reaction and immunohistochemical staining, respectively. Results. Antisense oligonucleotides targeting PCNA inhibited IL-1-stimulated fibroblast proliferation, whereas sense oligonucleotides had no effect. Both mRNA and protein levels of PCNA were suppressed in the cells treated with antisense oligonucleotides, indicating that the antiproliferative effect was occurring through an antisense mechanism. Conclusion. These results suggest that antisense strategies designed to suppress PCNA expression have potential use as therapeutic agents for RA.

Original languageEnglish
Pages (from-to)1292-1297
Number of pages6
JournalArthritis and Rheumatism
Volume40
Issue number7
DOIs
Publication statusPublished - Jul 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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