title: Effects of UCP4 on the Proliferation and Apoptosis of Chondrocytes: Its Possible Involvement and Regulation in Osteoarthritis.
abstract: Reactive oxygen species (ROS)-induced chondrocytes apoptosis plays a key role in osteoarthritis (OA) pathogenesis. Uncoupling protein 4 (UCP4) can protect cells against oxidative stress via reducing ROS production and cell apoptosis. Here, silencing of UCP4 in primary chondrocytes significantly inhibited cell survival, but induced ROS production and cell apoptosis. UCP4 mRNA of cartilage tissues was decreased in osteoarthritis patients, which was negatively correlated with synovial fluid (SF) leptin concentration. Moreover, leptin treatment (5, 10 and 20 ng/ml) of primary cultured chondrocytes significantly decreased mRNA and protein levels of UCP4, but increased ROS production and cell apoptosis in a dose-dependent manner. The effects of leptin treatment (20 ng/ml) on chondrocytes was partially reversed by ectopic expression of UCP4. More importantly, intraarticularly injection of UCP4 adenovirus remarkably alleviate OA progression and cell apoptosis in a rat OA model induced by anterior cruciate ligament transection (ACLT). In conclusion, UCP4, whose expression was suppressed by leptin, may be involved in the ROS production and apoptosis of chondrocytes, thus contributing to the OA pathogenesis.
authors.affiliation: Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, China.|Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, China.|Zhejiang Chinese Medical University, Hangzhou, China.|Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, China.|Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guangnan
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, China.|Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, China.|Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Luwei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou, China.|Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou, China.|Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Peijian
authors.initials: P
authors.lastname: Tong
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D000071245:Mitochondrial Uncoupling Proteins; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C117577:SLC25A27 protein, human; C494853:Slc25a27 protein, rat