TMF protects chondrocytes from ER stress-induced apoptosis by down-regulating GSK-3β.
Endoplasmic reticulum (ER) stress-induced chondrocyte apoptosis plays a critical role in osteoarthritis cartilage degeneration. Previous studies showed that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited chondroprotective activity through inhibiting PGE2-induced ER stress and down regulating the expression of GSK-3β. To further investigate the role of GSK-3β in ER stress-induced chondrocytes apoptosis and the protective role of TMF, GSK-3β siRNA and pcDNA3.1-myc-GSK-3β were employed to knock down and overexpress GSK-3β, respectively, in chondrocytes. Results showed that TM-induced ER stress significantly promoted chondrocytes apoptosis. These could be effectively reversed by GSK-3β deficiency, while GSK-3β overexpression significantly up regulated ER stress and increased chondrocytes apoptosis. In addition, TMF down regulated the expression of GSK-3β and inhibited ER stress-induced chondrocytes apoptosis. Collectively, TMF is a potential natural compound with chondroprotective property through inhibition of ER stress-induced apoptosis with down regulation of GSK-3β.
Department of Respiratory Medicine, the First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
Xiaoliang
X
Yuan
College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China.
Linfu
L
Li
College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China.
Weimei
W
Shi
College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China.
Hai
H
Liu
College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China.
Xianhua
X
Huang
School of Basic Medicine, Gannan Medical University, Ganzhou, 341000 China.
Zhiping
Z
Liu
College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China. Electronic address: longhwu@hotmail.com.
Longhuo
L
Wu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D007769:Lactams / Q000494:pharmacology*; D016712:Mupirocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D007769:Lactams; D020011:Protective Agents; D034741:RNA, Small Interfering; C107034:thiomarinol F; D016712:Mupirocin; D000071679:Glycogen Synthase Kinase 3 beta
Chondrocytes apoptosis; ER stress; GSK-3β; TMF