Overexpression of ADAMTS-7 leads to accelerated initiation and progression of collagen-induced arthritis in mice
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The aim of the present study is to determine whether ADAMTS-7 contributes to the onset and severity of joint inflammation in the pathogenesis of inflammatory arthritis. ADAMTS-7 was found to be elevated in the course of collagen-induced arthritis (CIA). ADAMTS-7 transgenic (TG) mice were more susceptible to the induction of CIA. The onset of CIA was accelerated and the arthritic severity was increased in TG mice compared to wild-type mice. The overall incidence was also significantly higher in TG mice. In addition, arthritic TG mice displayed significantly higher clinical and histological arthritis scores. The COMP degradative fragments were significantly elevated in articular cartilage and sera in CIA models of TG mice. Furthermore, the production of tumor necrosis factor-alpha and interleukin-17 was also increased in serum and draining lymph nodes of arthritic TG mice. Therefore, these data provided the in vivo evidence, suggesting that ADAMTS-7 may play an important role in the pathogenesis of inflammatory arthritis, and that inhibition of ADAMTS-7 may be a potential target to ameliorate the severity of inflammatory arthritis.
KeywordsADAMTS-7 COMP Transgenic mice Collagen-induced arthritis TNF-α
This work was supported partly by NIH research Grants R01AR062207, R01AR061484, R56AI100901, and a Disease Targeted Research Grant from Rheumatology Research Foundation (to C. J. Liu). The founding resources had no involvement in study design, in the collection and analysis of data.
Conflict of interest
The authors have no financial conflicts of interest.