title: Lentiviral vector-mediated over-expression of Sox9 protected chondrocytes from IL-1β induced degeneration and apoptosis.
abstract: To explore whether the over-expression of Sry-related HMG box (Sox9) in degenerative chondrocytes is able to improve cell regeneration and protects cells from inflammation induced apoptosis, we generated a Sox9 over-expressing vector delivery system in which the Sox9 gene was inserted into a lentiviral vector. After infecting mouse chondrocytes with the Sox9-encoding vector, we observed a high level of gene transduction efficiency and achieved a high level of Sox9 expression in the infected chondrocytes. To explore whether over-expression of Sox9 is able to induce cell regeneration and improve cell survival, we induced Sox9 over-expression by lentiviral vector infection 48 hours before IL-1β treatment. The cells were infected with the reporter gene GFP-encoded lentiviral vector as a negative control or left uninfected. 48-hours after IL-1β treatment, the chrondrocytes treated with IL-1β alone, underwent a degenerative process, with elevated expression of MMP-3, MMP-13, ADAMTS-5 and ALP, but the cell specific anabolic proteins collagen II and aggrecan were significantly suppressed. The cells infected with the GFP reporter vector had no increased regeneration after IL-1β treatment. The results indicated that Sox9 is an important chondrocyte transcription factor, promoting chondrocyte regeneration and cell survival, which were mediated through affecting multiple cell differentiation as well as anti-apoptotic signaling pathways.
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, P. R. China.
authors.forename: Huading
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Joint Surgery, Third Affiliated Hospital of Southern Medical University Guangzhou 510630, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, P. R. China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, P. R. China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Lian
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, P. R. China.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Sun Yat-Sen University Guangzhou, P. R. China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhao
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005822:Genetic Vectors; D053583:Interleukin-1beta / Q000494:pharmacology*; D016086:Lentivirus; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D051722:ADAM Proteins; C093560:Adam5 protein, mouse; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3
keywords: Osteoarthritis; Sox9; cell degeneration; cell survival; chondrocyte