title: YAP-mediated mechanotransduction regulates osteogenic and adipogenic differentiation of BMSCs on hierarchical structure.
abstract: Hierarchical structure mimicking the natural bone microenvironment has been considered as a promising platform to regulate cell functions. We have previously fabricated hierarchical macropore/nanowire structure and evidence has shown that it can better manipulate the cytoskeleton status and osteogenic performance of osteoblasts. However, how cues of hierarchical structure are translated and ultimately linked to BMSC lineage commitment have still remained elusive, which hinders the accurate knowledge and further development of the hierarchical structure. In this study, bone marrow-derived mesenchymal stem cells (BMSCs) fate on hierarchical structure was investigated as well as the detailed mechanisms. It was shown that well-developed cytoskeleton and focal adhesion were observed for BMSCs on hierarchical structure, which was accompanied by enhanced osteogenic and depressed adipogenic potential. Evidence of increased YAP activity and nuclear translocation were exhibited on hierarchical structure and YAP knockdown inhibited osteogenic differentiation and promoted adipogenic differentiation induced by hierarchical structure. Further remove of cytoskeleton tension inhibited YAP function, which confirmed the key role of YAP-mediated mechanotransduction in the BMSC differentiation. These results together provide information of the stem cell fate commitment on hierarchical structure and a promising approach to design advanced biomaterials by focusing on specific mechanotransduction process.
authors.affiliation: Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences,1295 Dingxi Road, Shanghai 200050, PR China; Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China; University of Chinese Academy of Sciences,19 Yuquan Road, Beijing 100049, PR China.
authors.forename: Houhua
authors.initials: H
authors.lastname: Pan
authors.affiliation: Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences,1295 Dingxi Road, Shanghai 200050, PR China.
authors.forename: Youtao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences,1295 Dingxi Road, Shanghai 200050, PR China.
authors.forename: Zequan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences,1295 Dingxi Road, Shanghai 200050, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences,1295 Dingxi Road, Shanghai 200050, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences,1295 Dingxi Road, Shanghai 200050, PR China. Electronic address: xbzheng@mail.sic.ac.cn.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China. Electronic address: chillow@163.com.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing
keywords: BMSC; Differentiation; Hierarchical structure; Mechanotransduction; YAP