title: Integrin β1 Gene Therapy Enhances in Vitro Creation of Tissue-Engineered Cartilage Under Periodic Mechanical Stress.
abstract: OBJECTIVE
  Periodic mechanical stress activates integrin β1-initiated signal pathways to promote chondrocyte proliferation and matrix synthesis. Integrin β1 overexpression has been demonstrated to play important roles in improving the activities and functions of several non-chondrocytic cell types. Therefore, in the current study, we evaluated the effects of integrin β1 up-regulation on periodic mechanical stress-induced chondrocyte proliferation, matrix synthesis and ERK1/2 phosphorylation in chondrocyte monolayer culture, and evaluated the quality of tissue-engineered cartilage constructed in vitro under periodic mechanical stress combined with integrin β1 up-regulation.
  
  
  RESULTS
  Our results revealed that under periodic mechanical stress, pre-treatment with integrin β1-wild type vector significantly enhanced chondrocyte proliferation and matrix synthesis and promoted ERK1/2 phosphorylation in comparison to mock transfectants. Furthermore, when chondrocytes were seeded in PLGA scaffolds, more accumulated GAG and type II collagen tissue were detected after Lv-integrin β1 transfection compared with sham controls exposed to periodic mechanical stress. In contrast, in the Lv-shRNA-integrin β1 group, the opposite results were observed.
  
  
  CONCLUSIONS
  Our findings collectively suggest that in addition to periodic mechanical stress, integrin β1 up-regulation in chondrocytes could further improve the quality of tissue-engineered cartilage.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liang
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Weiding
authors.initials: W
authors.lastname: Cui
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhefeng
authors.initials: Z
authors.lastname: Chen
authors.forename: Qijia
authors.initials: Q
authors.lastname: Zhou
authors.forename: Shun
authors.initials: S
authors.lastname: Xu
authors.forename: Chenjun
authors.initials: C
authors.lastname: Zhai
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy; D019012:Integrin beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013314:Stress, Mechanical; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D015854:Up-Regulation
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D019012:Integrin beta1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3