兰州大学机构库
Leptin Potentiates Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling
2020-03-09
Online publication date2020-03
Source PublicationSTEM CELLS AND DEVELOPMENT   Impact Factor & Quartile Of Published Year  The Latest Impact Factor & Quartile
ISSN1547-3287
EISSN1557-8534
Volume29Issue:8Pages:498-510
page numbers13
AbstractMesenchymal stem cells (MSCs) are multipotent progenitors that have the ability to differentiate into multiple lineages, including bone, cartilage, and fat. We previously demonstrated that the least known bone morphogenetic protein (BMP)9 (also known as growth differentiation factor 2) is one of the potent osteogenic factors that can induce both osteogenic and adipogenic differentiation of MSCs. Nonetheless, the molecular mechanism underlying BMP9 action remains to be fully understood. Leptin is an adipocyte-derived hormone in direct proportion to the amount of body fat, and exerts pleiotropic functions, such as regulating energy metabolism, bone mass, and mineral density. In this study, we investigate the potential effect of leptin signaling on BMP9-induced osteogenic differentiation of MSCs. We found that exogenous leptin potentiated BMP9-induced osteogenic differentiation of MSCs both in vitro and in vivo, while inhibiting BMP9-induced adipogenic differentiation. BMP9 was shown to induce the expression of leptin and leptin receptor in MSCs, while exogenous leptin upregulated BMP9 expression in less differentiated MSCs. Mechanistically, we demonstrated that a blockade of JAK signaling effectively blunted leptin-potentiated osteogenic differentiation induced by BMP9. Taken together, our results strongly suggest that leptin may potentiate BMP9-induced osteogenesis by cross-regulating BMP9 signaling through the JAK/STAT signaling pathway in MSCs. Thus, it is conceivable that a combined use of BMP9 and leptin may be explored as a novel approach to enhancing efficacious bone regeneration and fracture healing.
Keywordmesenchymal stem cells BMP9 leptin osteogenesis osteogenic differentiation adipogenesis bone mass
PublisherMARY ANN LIEBERT, INC
DOI10.1089/scd.2019.0292
Indexed BySCIE
Language英语
Funding ProjectNational Institutes of Health[CA226303] ; United States Department of Defense[OR130096] ; Medical Scientist Training Program of the National Institutes of Health[T32 GM007281] ; University of Chicago Cancer Center Support Grant[P30CA014599] ; National Center for Advancing Translational Sciences of the National Institutes of Health[UL1 TR000430]
WOS Research AreaCell Biology ; Hematology ; Research & Experimental Medicine ; Transplantation
WOS SubjectCell & Tissue Engineering ; Hematology ; Medicine, Research & Experimental ; Transplantation
WOS IDWOS:000525467100001
PublisherMARY ANN LIEBERT, INC
Original Document TypeArticle ; Early Access
PMID 32041483
Citation statistics
Document Type期刊论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/417506
Collection兰州大学
第一临床医学院
第二临床医学院
Corresponding AuthorXia, Yayi; He, Tong-Chuan
Affiliation
1.Lanzhou Univ, Hosp 1, Inst Bone & Joint Res, Dept Orthopaed Surg, Lanzhou, Peoples R China
2.Lanzhou Univ, Hosp 2, Inst Bone & Joint Res, Dept Orthopaed Surg, Lanzhou 730030, Peoples R China
3.Lanzhou Univ, Hosp 1, Inst Bone & Joint Res, Dept Obstet & Gynecol, Lanzhou, Peoples R China
4.Lanzhou Univ, Hosp 2, Inst Bone & Joint Res, Dept Obstet & Gynecol, Lanzhou, Peoples R China
5.Univ Chicago, Med Ctr, Mol Oncol Lab, Dept Orthopaed Surg & Rehabil Med, 5841 South Maryland Ave,MC3079, Chicago, IL 60637 USA
6.Chongqing Med Univ, Minist Educ, Key Lab Diagnost Med, Chongqing, Peoples R China
7.Chongqing Med Univ, Sch Lab Med, Chongqing, Peoples R China
8.Chongqing Med Univ, Affiliated Hosp 1, Dept Breast Surg, Chongqing, Peoples R China
9.Chongqing Med Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Chongqing, Peoples R China
10.Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing, Peoples R China
11.Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing, Peoples R China
12.Sichuan Univ, West China Hosp, Dept Burn & Plast Surg, Chengdu, Peoples R China
13.Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Orthopaed Surg, Guangzhou, Peoples R China
14.Wuhan Univ, Affiliated Zhongnan Hosp, Dept Orthopaed Surg, Wuhan, Peoples R China
15.Wuhan Univ, Affiliated Zhongnan Hosp, Dept Neurosurg, Wuhan, Peoples R China
16.Nanjing Med Univ, BenQ Med Ctr, Dept Orthopaed Surg, Nanjing, Peoples R China
17.Qingdao Univ, Affiliated Hosp, Dept Orthopaed Surg, Qingdao, Peoples R China
18.Chongqing Gen Hosp, Dept Lab Diagnost Med, Chongqing, Peoples R China
19.Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Orthopaed Surg, Wuhan, Peoples R China
20.Cent South Univ, Xiangya Hosp 2, Dept Spine Surg, Changsha, Peoples R China
First Author AffilicationFirst Clinical School;  Second Clinical School
Corresponding Author AffilicationFirst Clinical School;  Second Clinical School
First Signature AffilicationFirst Clinical School
Recommended Citation
GB/T 7714
Zhang, Bo,Yang, Lijuan,Zeng, Zongyue,et al. Leptin Potentiates Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling[J]. STEM CELLS AND DEVELOPMENT,2020,29(8):498-510.
APA Zhang, Bo.,Yang, Lijuan.,Zeng, Zongyue.,Feng, Yixiao.,Wang, Xi.,...&He, Tong-Chuan.(2020).Leptin Potentiates Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling.STEM CELLS AND DEVELOPMENT,29(8),498-510.
MLA Zhang, Bo,et al."Leptin Potentiates Bone Morphogenetic Protein 9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells Through the Activation of JAK/STAT Signaling".STEM CELLS AND DEVELOPMENT 29.8(2020):498-510.
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