Role of Oct-4 in rheumatoid arthritis

  • 木 芭娜

Student thesis: Master's Thesis

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that may affect many tissues and organs especially flexible (synovial) joints The process involves an inflammatory response of the joints (synovium) to swelling (hyperplasia) of synovial cells excess synovial fluid and the development of fibrous tissue (pannus) in the synovium Autoimmunity plays a critical role in RA and RA is considered a systemic autoimmune disease Oct-4 is a homeodomain transcription factor of the POU family This protein is critically involved in the selfrenewal of undifferentiated embryonic stem cells Oct-4 may play a role in systemic rheumatic diseases IL-23 plays an important part in the inflammatory response against infection It promotes upregulation of the matrix metalloprotease- 9 (MMP-9) increases angiogenesis and reduces CD8+ T cell infiltration Our previous data have shown that Oct-4 expression is significantly higher in patients with RA and in ankle joints of mice with collagen-induced arthritis (CIA) than in patients with osteoarthritis (OA) and normal mice Therefore in this study we first demonstrate immunohistochemically that Oct-4 and phosphorylated Stat4 (p-Stat4) were highly expressed in the synovial tissue of CIA mice IL- 23p19 expression was also upregulated in the ankle joints of CIA mice by dissecting with immunoblot analysis Furthermore We used lentiviral vector expressing short hairpin RNA (shRNA) specific to Oct-4 (LVshOct-4) for intra-articular administration to CIA mice and the expression of Oct-4 was greatly reduced after the treatment with LVshOct-4 Histologic score was also lower in the LVshOct-4-treated CIA ankle joints than the control counterparts In conclusion this study may reveal a new concept that Oct-4 is a positive contributor to the pathogenesis of RA and reduction of Oct-4 provides a novel therapeutic approach for the treatment of RA in the future
Date of Award2014 Aug 21
Original languageEnglish
SupervisorChao-Liang Wu (Supervisor)

Cite this

'