title: c-Jun transactivates Puma gene expression to promote osteoarthritis.
abstract: Osteoarthritis (OA) is a chronic degenerative joint disorder in which genetic, hormonal, mechanical and ageing factors affect its progression. Current studies are focusing on chondrocytes as a key mediator of OA at a cellular level. however, the mechanism underlying chondrocyte apoptosis remains unclear. PUMA is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family and is involved in a large number of physiological and pathological processes. In the present study, we examined whether PUMA has a role in IL-1β-induced apoptosis and whether the c-Jun N-terminal kinase (JNK)/c-Jun pathway mediates the induction of PUMA, thus contributing to chondrocyte apoptosis. The results demonstrated an increase in PUMA protein and mRNA levels in cultured mouse chondrocytes following 4 h of IL-1β treatment. Furthermore, this upregulation of PUMA was critical for chondrocyte apoptosis as knockdown of PUMA using PUMA-specific siRNA significantly reduced apoptosis in cultured cells. Upon pharmacological inhibition of the JNK/c-Jun pathway with CE11004 or SP600125, the expression of PUMA was notably suppressed with a concomitant decrease in apoptosis observed in IL-1β-treated chondrocytes. Also, immunohistochemical studies revealed that the PUMA and c-Jun proteins were upregulated in chondrocytes from the articular cartilage of OA patients. Together, these data suggest a role for PUMA and the JNK/c-Jun pathway in the regulation of chondrocyte apoptosis during OA.
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Huading
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hou
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yongkai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D053583:Interleukin-1beta; C488588:PUMA protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D048031:JNK Mitogen-Activated Protein Kinases