Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1935086 | Biochemical and Biophysical Research Communications | 2008 | 5 Pages |
Abstract
Aggrecanase-1/a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS)-4 and aggrecanase-2/ADAMTS-5 have been shown to play crucial roles in cartilage destruction in arthritic diseases, including rheumatoid arthritis and osteoarthritis. In this study, we examined the effects of nobiletin, a citrus polymethoxy flavone, on the expression and production of ADAMTS-4 and -5 in vitro and in vivo. Nobiletin (16-64 μM) interfered with the interleukin (IL)-1β-mediated ADAMTS-4 and -5 mRNA expression in cultured human synovial fibroblasts. Furthermore, intraperitoneal administration of nobiletin (15, 30, and 60 mg/kg) also suppressed ADAMTS-4 and -5 mRNA expression in the joint tissues of collagen-induced arthritic (CIA) mice. Immunohistochemical analysis using an antibody against aggrecan neoepitope (NVTEGE373) revealed that aggrecanase-mediated degradation of aggrecan in cartilage was effectively inhibited by nobiletin. These results provide novel evidence that nobiletin effectively interferes with gene expression of ADAMTS-4 and -5, and thereby prevents cartilage destruction in CIA mice.
Keywords
TNFMMPPBSIGDADAMTSCOXFBSGAPDHaggrecanasecollagen-induced arthritisRheumatoid arthritiscyclooxygenaseOsteoarthritisinflammationinterleukinreverse transcriptionTIMPfetal bovine serumCIACartilagetumor necrosis factorExtracellular matrixmatrix metalloproteinaseMEKPhosphate-buffered salineTissue inhibitor of metalloproteinasesNobiletinpolymerase chain reactionPCRprostaglandinglyceraldehydes-3-phosphate dehydrogenase
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Authors
Keisuke Imada, Na Lin, Chunfang Liu, Aiping Lu, Weiheng Chen, Masamichi Yano, Takashi Sato, Akira Ito,