title: Bone morphogenetic protein-10 induces cardiomyocyte proliferation and improves cardiac function after myocardial infarction.
abstract: Heart disease is among the leading causes of death worldwide, and the limited proliferation of mammalian cardiomyocytes prevents heart regeneration in response to injury. Bone morphogenetic protein-10 (BMP10) exerts multiple roles in various developmental events; however, the effect of BMP10 and the underlying mechanism involved in cardiac repair remains unclear. After stimulation with the recombinant BMP10, an obvious dose-dependent cardiomyocyte proliferation and reentry of differentiated mammalian cardiomyocytes into the cell cycle was observed. Furthermore, BMP10 stimulation strikingly enhanced Tbx20 expression. Further analysis demonstrated that T-box 20 (Tbx20) was involved in BMP10-induced proliferation of differentiated cardiomyocytes as preconditioning with Tbx20 siRNA significantly attenuated BMP10-induced DNA synthesis. In vivo, BMP10 induced rat cardiomyocyte DNA synthesis and cytokinesis. After myocardial infarction (MI), BMP10 stimulated cardiomyocyte cell-cycle reentry and mitosis, resulting in the decrease of infarct size and improvement of cardiac repair. Taken together, these data indicated that BMP10 stimulated cardiomyocyte proliferation and repaired cardiac function after heart injury. Consequently, BMP10 may be a potential target for innovative strategies against heart failure.
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Shun
authors.initials: S
authors.lastname: Qi
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Hao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D015316:Genetic Therapy; D006321:Heart / Q000503:physiopathology*; D006334:Heart Function Tests; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; C525708:Bmp1 protein, rat; D055395:Bone Morphogenetic Protein 1
keywords: BMP10; CARDIAC REPAIR; CARDIOMYOCYTE PROLIFERATION; MYOCARDIAL INFARCTION