title: The interaction between β1 integrins and ERK1/2 in osteogenic differentiation of human mesenchymal stem cells under fluid shear stress modelled by a perfusion system.
abstract: Fluid shear stress (FSS) is an important biomechanical factor regulating the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and is therefore widely used in bone tissue engineering. However, the mechanotransduction of FSS in hMSCs remains largely unknown. As β1 integrins are considered to be important mechanoreceptors in other cells, we suspect that β1 integrins should also be important for hMSCs to sense the stimulation of FSS. We used a perfusion culture system to produce FSS loading on hMSCs seeded in PLGA three-dimensional (3D) scaffolds and investigated the roles of β1 integrins, FAK and ERK1/2 in FSS-induced osteogenic differentiation of hMSCs. Our results showed that FSS not only markedly increased ALP activity and the expression of ALP, OCN, Runx2 and COLIα genes but also significantly enhanced the phosphorylation of ERK1/2, Runx2 and FAK. FSS-induced activation of ERK1/2 and FAK was inhibited by blockade of the connection between β1 integrins and ECM with RGDS peptide and integrins β1 monoclonal antibody. Our study also found that FSS could upregulate the expression level of β1 integrins and that this upregulation could be abolished by PD98059. Further investigation indicated that FSS-activated ERK1/2 led to the phosphorylation of IκBα and NFκB p65. The activation of NFκB p65 resulted in the upregulation of β1 integrin expression. Therefore, it could be inferred that β1 integrins should sense the stimulation of FSS and thus activate ERK1/2 through activating of FAK, and FSS-activated ERK1/2 feedback to upregulate the expression of β1 integrins through activating NFκB.
authors.affiliation: Institute of Cell Biology, College of Life Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China; Departmant of biology, Ningde Normal University, Ningde, Fujian, 352101, People's Republic of China.
authors.forename: Liyue
authors.initials: L
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Zong
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.forename: Zihua
authors.initials: Z
authors.lastname: Tang
authors.forename: Jiarong
authors.initials: J
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zheng
authors.forename: Xiangming
authors.initials: X
authors.lastname: Tong
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
authors.forename: Jinfu
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D019344:Lactic Acid / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008875:Middle Aged; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010477:Perfusion; D010766:Phosphorylation / Q000187:drug effects; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D033081:Shear Strength; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry; D051996:Transcription Factor RelA / Q000378:metabolism; D055815:Young Adult
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D020672:I-kappa B Proteins; D019012:Integrin beta1; C000606204:NFKBIA protein, human; D051996:Transcription Factor RelA; D015675:Osteocalcin; D000072000:NF-KappaB Inhibitor alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase