title: Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells.
abstract: Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Electronic address: liulingling2012@163.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Electronic address: qing.luo@cqu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Electronic address: sunjhemail@163.com.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Electronic address: leaf13332@163.com.
authors.forename: Aoli
authors.initials: A
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Electronic address: shiyis@cqu.edu.cn.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: ju@mech.nagoya-u.ac.jp.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ju
authors.affiliation: Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan. Electronic address: morita@mech.nagoya-u.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, People's Republic of China. Electronic address: song@cqu.edu.cn.
authors.forename: Guanbin
authors.initials: G
authors.lastname: Song
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D053495:Osteopontin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053495:Osteopontin; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Bone marrow-derived mesenchymal stem cells (BMSCs); FAK-ERK1/2 signaling; Lamin A/C; Migration; Nuclear mechanics; Osteopontin