Overexpression of ADAMTS-7 leads to accelerated initiation and progression of collagen-induced arthritis in mice.
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.
Department of Orthopaedic Surgery, New York University Medical Center, Rm 1608, HJD, 301 East 17th Street, New York, NY, 10003, USA.
Yuying
Y
Zhang
Fanhua
F
Wei
Chuan-Ju
CJ
Liu
D051722:ADAM Proteins / Q000235:genetics*; D000071118:ADAMTS7 Protein; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D064236:Cartilage Oligomeric Matrix Protein / Q000097:blood; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000633:toxicity; D018450:Disease Progression; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D064236:Cartilage Oligomeric Matrix Protein; C508717:IL17A protein, human; D020381:Interleukin-17; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; C496264:Adamts7 protein, mouse