title: Role of PPARα in down-regulating AGE-induced TGF-β and MMP-9 expressions in chondrocytes.
abstract: Peroxisome proliferator-activated receptor is closely associated with the pathogenesis of osteoarthritis. The level of exogenous advanced glycation end-products (AGEs) in articular cartilage is highly associated with the severity of osteoarthritic lesions. However, their interactions and role in promoting osteoarthritisprogression remain unclear. Here, we investigated the effect of AGEs on transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 expression, and discussed the correlation between AGEs and osteoarthritis, possible signaling pathways and mechanism in rabbit chondrocytes. TGF-β and MMP-9 mRNA and protein expression, catalase (CAT) and superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were analyzed in chondrocytes treated with different concentrations of AGEs using RT-PCR and/or western blot; we detected NF-κB nuclear translocation by immunofluorescence. AGE treatment significantly increased TGF-β and MMP-9 mRNA and protein expression compared to controls (P < 0.01) in a dose-dependent manner (highest at 100 μg/mL). AGE-induced TGF-β and MMP-9 expressions in chondrocytes were significantly inhibited by anti-RAGE and PDTC (0.1 mM) treatment (P < 0.01). Furthermore, AGE-treatment significantly decreased CAT and SOD activity and increased MDA levels in a concentration-dependent manner compared to controls (P < 0.05), significantly promoting NF-κB nuclear translocation. AGE significantly inhibited the increased expression of TGF-β and MMP- 9, and induced chondrocyte damage. Its mechanism is associated with RAGE activation, increased ROS expression, and activation of the NF- κB signaling pathways.
authors.affiliation: Department of Bone Trauma, Inner Mongolia People's Hospital, Hohhot, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Traumatic Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Bone Trauma, Inner Mongolia People's Hospital, Hohhot, China.
authors.forename: G W
authors.initials: GW
authors.lastname: Sun
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D047493:PPAR alpha; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9