Evidence map›Paper›PMID 30353129›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2019

BMP9-induced osteoblastic differentiation requires functional Notch signaling in mesenchymal stem cells.

Jing Cui, Wenwen Zhang, Enyi Huang, Jia Wang, Junyi Liao, Ruidong Li, Xinyi Yu, Chen Zhao, Zongyue Zeng, Yi Shu and 28 more

Open access · hybridAbstract read
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 77 citations in OpenAlex.

  1. The Liver-Bone Axis in Steatotic Liver Disease.Calcified tissue international · 2026
    Review
  2. Article
  3. Article
  4. Genes & diseases · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Long noncoding RNA (lncRNA)Genes & diseases · 2023
    Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 7 institutions in 2 countries.

Jing CuiKey Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wenwen ZhangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA. 187254894@qq.com.
Enyi HuangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Jia WangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Junyi LiaoMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Ruidong LiMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Xinyi YuMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Chen ZhaoMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Zongyue ZengMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Yi ShuMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Ruyi ZhangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Shujuan YanMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Jiayan LeiMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Chao YangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Ke WuMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Ying WuMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Shifeng HuangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Xiaojuan JiMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Alexander LiMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Cheng GongMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Chengfu YuanMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Linghuan ZhangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Wei LiuMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Bo HuangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Yixiao FengMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Liping AnMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Bo ZhangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Zhengyu DaiMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Yi ShenMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Wenping LuoMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Xi WangMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Ailong HuangKey Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Hue H LuuMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Russell R ReidMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Jennifer Moriatis WolfMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Gopal ThinakaranDepartment of Neurobiology, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Michael J LeeMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA.
Tong-Chuan HeMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA. tche@uchicago.edu.
University of Chicago Medical Center · USChongqing Medical University · CNMolecular Oncology (United States) · USBeijing University of Chinese Medicine · CNDalian Medical University · CNLanzhou University · CNWuhan University · CN

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1M
Re-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2M
Differential Effects of BMPs on the Healing of Craniofacial DefectsK08DE020140 · NIDCR · UNIVERSITY OF CHICAGO · PI REID, RUSSELL R. · 2009 to 2013
$624k
A genomewide discovery of chemoresistance-associated noncoding RNAs in human cancersR21CA226303 · NCI · UNIVERSITY OF CHICAGO · PI HE, TONG-CHUAN · 2018 to 2019
$381k
NCATS NIH HHS UL1 TR000430NCI NIH HHS P30 CA014599NCI NIH HHS R21 CA226303NIDCR NIH HHS K08 DE020140
6 · The paper itself

Abstract

Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into multiple lineages including osteoblastic lineage. Osteogenic differentiation of MSCs is a cascade that recapitulates most, if not all, of the molecular events occurring during embryonic skeletal development, which is regulated by numerous signaling pathways including bone morphogenetic proteins (BMPs). Through a comprehensive analysis of the osteogenic activity, we previously demonstrated that BMP9 is the most potent BMP for inducing bone formation from MSCs both in vitro and in vivo. However, as one of the least studied BMPs, the essential mediators of BMP9-induced osteogenic signaling remain elusive. Here we show that BMP9-induced osteogenic signaling in MSCs requires intact Notch signaling. While the expression of Notch receptors and ligands are readily detectable in MSCs, Notch inhibitor and dominant-negative Notch1 effectively inhibit BMP9-induced osteogenic differentiation in vitro and ectopic bone formation in vivo. Genetic disruption of Notch pathway severely impairs BMP9-induced osteogenic differentiation and ectopic bone formation from MSCs. Furthermore, while BMP9-induced expression of early-responsive genes is not affected by defective Notch signaling, BMP9 upregulates the expression of Notch receptors and ligands at the intermediate stage of osteogenic differentiation. Taken together, these results demonstrate that Notch signaling may play an essential role in coordinating BMP9-induced osteogenic differentiation of MSCs.

Indexed as

OsteogenesisCell DifferentiationGrowth Differentiation Factor 2Growth Differentiation FactorsHEK293 CellsHumansMesenchymal Stem CellsReceptors, NotchSignal TransductionUp-RegulationGDF2 protein, humanGrowth Differentiation Factor 2Growth Differentiation FactorsReceptors, Notch

Identifiers

PMID30353129
PMCPMC6300564
OpenAlexW2896980091

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.