BMP-2 Signaling and Mechanotransduction Synergize to Drive Osteogenic Differentiation via YAP/TAZ

被引：113

作者：

Wei, Qiang ^{[1
,2
,3
]}

Holle, Andrew ^{[2
,3
]}

Li, Jie ^{[2
,3
]}

Posa, Francesca ^{[2
,3
,4
]}

Biagioni, Francesca ^{[5
]}

Croci, Ottavio ^{[5
]}

Benk, Amelie S. ^{[2
,3
]}

Young, Jennifer ^{[2
,3
]}

Noureddine, Fatima ^{[2
,3
]}

Deng, Jie ^{[1
,2
,3
]}

Zhang, Man ^{[1
,2
,3
]}

Inman, Gareth J. ^{[6
,7
]}

Spatz, Joachim P. ^{[2
,3
]}

Campaner, Stefano ^{[5
]}

Cavalcanti-Adam, Elisabetta A. ^{[2
,3
,8
]}

机构：

[1] Sichuan Univ, State Key Lab Polymer Mat & Engn, Coll Polymer Sci & Engn, Chengdu 610065, Peoples R China

[2] Max Planck Inst Med Res, Dept Cellular Biophys, Jahnstr 29, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, Dept Biophys Chem, INF 253, D-69120 Heidelberg, Germany

[4] Univ Foggia, Med Sch, Dept Clin & Expt Med, I-71122 Foggia, Italy

[5] Ist Italian Tecnol IIT, Ctr Genom Sci IIT SEMM, I-20139 Milan, Italy

[6] Canc Res UK Beatson Inst, Growth Factor Signalling & Squamous Canc, Garscube Estate, Glasgow G61 1BD, Lanark, Scotland

[7] Univ Glasgow, Inst Canc Sci, Glasgow G12 8QQ, Lanark, Scotland

[8] MPI Med Res, Cent Sci Facil Cellular Biotechnol, Jahnstr 29, D-69120 Heidelberg, Germany

来源：

ADVANCED SCIENCE | 2020年 / 7卷 / 15期

基金：

中国国家自然科学基金;

关键词：

BMP-2; cell differentiation; mechanotransduction; signaling; YAP; TAZ; BONE MORPHOGENETIC PROTEIN-2; GROWTH-FACTOR; POLYMER-COATINGS; MATRIX STIFFNESS; CELL FATE; TGF-BETA; YAP; TAZ; INTEGRIN; ACTIVATION;

D O I：

10.1002/advs.201902931

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Growth factors and mechanical cues synergistically affect cellular functions, triggering a variety of signaling pathways. The molecular levels of such cooperative interactions are not fully understood. Due to its role in osteogenesis, the growth factor bone morphogenetic protein 2 (BMP-2) is of tremendous interest for bone regenerative medicine, osteoporosis therapeutics, and beyond. Here, contribution of BMP-2 signaling and extracellular mechanical cues to the osteogenic commitment of C2C12 cells is investigated. It is revealed that these two distinct pathways are integrated at the transcriptional level to provide multifactorial control of cell differentiation. The activation of osteogenic genes requires the cooperation of BMP-2 pathway-associated Smad1/5/8 heteromeric complexes and mechanosensitive YAP/TAZ translocation. It is further demonstrated that the Smad complexes remain bound onto and active on target genes, even after BMP-2 removal, suggesting that they act as a "molecular memory unit." Thus, synergistic stimulation with BMP-2 and mechanical cues drives osteogenic differentiation in a programmable fashion.

引用

页数：15

共 65 条

[21] BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity [J].