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.

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