Abstract:

Objective    To investigate the effects of estrogen on the disease development and the expressions of peptidylarginine deiminase 4 (PADI4) and thioredoxin domain containing protein 5 (TXNDC5) in collagen induced arthritis (CIA) models. Methods    Twenty-nine male Lewis rats were randomly divided into four groups: the healthy control group (group H, n=6）, the CIA group (group C, n=8), the CIA group treated with estrogen (group T, n=8) and the estrogen group（group E, n=7). CIA was induced subcutaneously with bovine type Ⅱcollagen (CⅡ) and estrogen treatment was operated during CⅡsensitization. ELISA was used to measure the levels of TNFα, IL-1β and VEGF in serum samples. Immunohistochemisty, Western-blot and real-time PCR were applied to detect the expressions of PADI4 and TXNDC5 in synovial membranes. Results    Compared with group C, the onset of CIA significantly delayed for 6 days (P=0.045) with no effects on inflammatory severity and incidence rates of the disease in group T; the serum levels of TNFαand IL-1βwere not evidently altered, but the level of VEGF was considerably increased (P=0.023). Synovial tissues in group T showed more hyperplasia with angiogenesis, in which PADI4 was mainly expressed in the lining and infiltrated inflammatory cells of synovium and TXNDC5 was mainly presented in the lining of synovium and endotheliocytes of capillaries. Estrogen pronouncedly stimulates the expression of TXNDC5 (P<0.05) rather than the expression of PADI4. Conclusion    Although estrogen can delay the onset of arthritis, it may stimulate angiogenesis in rheumatoid arthritis synovium via the up-regulation of TXNDC5.

Key words: Rheumatoid arthritis; Collagen-induced arthritis; Estrogen; Peptidylarginine deiminase 4