title: A controlled double-duration inducible gene expression system for cartilage tissue engineering.
abstract: Cartilage engineering that combines competent seeding cells and a compatible scaffold is increasingly gaining popularity and is potentially useful for the treatment of various bone and cartilage diseases. Intensive efforts have been made by researchers to improve the viability and functionality of seeding cells of engineered constructs that are implanted into damaged cartilage. Here, we designed an integrative system combining gene engineering and the controlled-release concept to solve the problems of both seeding cell viability and functionality through precisely regulating the anti-apoptotic gene bcl-2 in the short-term and the chondrogenic master regulator Sox9 in the long-term. Both in vitro and in vivo experiments demonstrated that our system enhances the cell viability and chondrogenic effects of the engineered scaffold after introduction of the system while restricting anti-apoptotic gene expression to only the early stage, thereby preventing potential oncogenic and overdose effects. Our system was designed to be modular and can also be readily adapted to other tissue engineering applications with minor modification.
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.|School of Life Sciences, Tsinghua University, Beijing, China.|Center for Synthetic &System Biology, Tsinghua University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.|School of Life Sciences, Tsinghua University, Beijing, China.|Center for Synthetic &System Biology, Tsinghua University, Beijing, China.
authors.forename: Junxiang
authors.initials: J
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.|School of Life Sciences, Tsinghua University, Beijing, China.|Center for Synthetic &System Biology, Tsinghua University, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.|School of Life Sciences, Tsinghua University, Beijing, China.|Center for Synthetic &System Biology, Tsinghua University, Beijing, China.
authors.forename: Daixu
authors.initials: D
authors.lastname: Wei
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.|School of Life Sciences, Tsinghua University, Beijing, China.|Center for Synthetic &System Biology, Tsinghua University, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.|School of Life Sciences, Tsinghua University, Beijing, China.|Center for Synthetic &System Biology, Tsinghua University, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D020219:Chondrogenesis; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C052617:Bcl2 protein, mouse