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Induction of predominant tenogenic phenotype in human dermal fibroblasts via synergistic effect of TGF-beta and elongated cell shape
Wang, Wenbo1; Li, Jie1; Wang, Keyun3,4; Zhang, Zhiyong1,2; Zhang, Wenjie1,2; Zhou, Guangdong1,2; Cao, Yilin1,2; Ye, Mingliang3,4; Zou, Hanfa3,4; Liu, Wei1,2
KeywordTenogenic Phenotype Cell Elongation Dermal Fibroblasts Tgf-beta Rock Activity
Source PublicationAMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
2016-03-01
ISSN0363-6143
DOI10.1152/ajpcell.00300.2015
Volume310Issue:5Pages:C357-C372
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectCell Biology ; Physiology
WOS Research AreaCell Biology ; Physiology
WOS KeywordMESENCHYMAL STEM-CELLS ; CRUCIATE LIGAMENT CELLS ; CYTOSKELETAL TENSION ; EPITHELIAL-CELLS ; GENE-EXPRESSION ; IN-VITRO ; DIFFERENTIATION ; TENDON ; NUCLEUS ; TISSUE
AbstractMicropattern topography is widely investigated for its role in mediating stem cell differentiation, but remains unexplored for phenotype switch between mature cell types. This study investigated the potential of inducing tenogenic phenotype in human dermal fibroblasts (hDFs) by artificial elongation of cultured cells. Our results showed that a parallel microgrooved topography could convert spread hDFs into an elongated shape and induce a predominant tenogenic phenotype as the expression of biomarkers was significantly enhanced, such as scleraxis, tenomodulin, collagens I, III, VI, and decorin. It also enhanced the expression of transforming growth factor (TGF)-beta 1, but not alpha-smooth muscle actin. Elongated hDFs failed to induce other phenotypes, such as adiopogenic, chondrogenic, neurogenic, and myogenic lineages. By contrast, no tenogenic phenotype could be induced in elongated human chondrocytes, although chondrogenic phenotype was inhibited. Exogenous TGF-beta 1 could enhance the tenogenic phenotype in elongated hDFs at low dose (2 ng/ml), but promoted myofibroblast transdifferentiation of hDFs at high dose (10 ng/ml), regardless of cell shape. Elongated shape also resulted in decreased RhoA activity and increased Rho-associated protein kinase (ROCK) activity. Antagonizing TGF-beta or inhibiting ROCK activity with Y27632 or depolymerizing actin with cytochalasin D could all significantly inhibit tenogenic phenotype induction, particularly in elongated hDFs. In conclusion, elongation of cultured dermal fibroblasts can induce a predominant tenogenic phenotype likely via synergistic effect of TGF-beta and cytoskeletal signaling.
Language英语
WOS IDWOS:000371299500004
PublisherAMER PHYSIOLOGICAL SOC
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/171039
Collection中国科学院大连化学物理研究所
Corresponding AuthorLiu, Wei
Affiliation1.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Shanghai Key Lab Tissue Engn, Dept Plast & Reconstruct Surg,Sch Med, Shanghai 200011, Peoples R China
2.Natl Tissue Engn Ctr China, Shanghai, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Analyt Chem, Natl Chromatog R&A Ctr, Dalian, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Wang, Wenbo,Li, Jie,Wang, Keyun,et al. Induction of predominant tenogenic phenotype in human dermal fibroblasts via synergistic effect of TGF-beta and elongated cell shape[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2016,310(5):C357-C372.
APA Wang, Wenbo.,Li, Jie.,Wang, Keyun.,Zhang, Zhiyong.,Zhang, Wenjie.,...&Liu, Wei.(2016).Induction of predominant tenogenic phenotype in human dermal fibroblasts via synergistic effect of TGF-beta and elongated cell shape.AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,310(5),C357-C372.
MLA Wang, Wenbo,et al."Induction of predominant tenogenic phenotype in human dermal fibroblasts via synergistic effect of TGF-beta and elongated cell shape".AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 310.5(2016):C357-C372.
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