Evidence map›Paper›PMID 30593824›Full record

ArticleThe American journal of pathology2019

Peroxisome Proliferator-Activated Receptor-γ Knockdown Impairs Bone Morphogenetic Protein-2-Induced Critical-Size Bone Defect Repair.

Chenchao Wang, Justine Tanjaya, Jia Shen, Soonchul Lee, Bharti Bisht, Hsin Chuan Pan, Shen Pang, Yulong Zhang, Emily A Berthiaume, Eric Chen and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

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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

15 authors at 2 institutions in 3 countries.

Chenchao WangDepartment of Plastic Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China; Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California; Division of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, and Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
Justine TanjayaDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Jia ShenDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Soonchul LeeDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California; Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
Bharti BishtDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Hsin Chuan PanDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Shen PangDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Yulong ZhangDepartments of Materials Science and Engineering, and Division of Advanced Prosthodontics, University of California, Los Angeles, Los Angeles, California.
Emily A BerthiaumeDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Eric ChenDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Andrew L Da LioDivision of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, and Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California.
Xinli ZhangDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Kang TingDental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California.
Shu GuoDepartment of Plastic Surgery, First Hospital of China Medical University, Shenyang, People's Republic of China. Electronic address: sguo@cmu.edu.cn.
Chia SooDivision of Plastic and Reconstructive Surgery, Department of Orthopaedic Surgery, and Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California. Electronic address: bsoo@ucla.edu.
University of California, Los Angeles · USFirst Hospital of China Medical University · CN

Funding

NELL-1's functional role in cartilage regenerationR01AR068835 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EASLEY, JEREMIAH, SOO, CHIA · 2015 to 2019
$2.2M
NELL-1 Systemic Therapy for OsteoporosisR01AR066782 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EASLEY, JEREMIAH, TING, KANG · 2014 to 2018
$2.0M
Wnt and PPARy Signaling in Nell-1 and BMP2 Mediated Bone RegenerationR01AR061399 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SOO, CHIA · 2012 to 2016
$1.7M
COMPARATIVE ANALYSIS OF Nell-1 vs BMPs IN CALVARIAL BONE REGENERATIONR21DE017711 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SOO, CHIA · 2007 to 2008
$435k
NIAMS NIH HHS R01 AR061399NIAMS NIH HHS R01 AR066782NIAMS NIH HHS R01 AR068835NIDCR NIH HHS R21 DE017711
6 · The paper itself

Abstract

The Food and Drug Administration-approved clinical dose (1.5 mg/mL) of bone morphogenetic protein-2 (BMP2) has been reported to induce significant adverse effects, including cyst-like adipose-infiltrated abnormal bone formation. These undesirable complications occur because of increased adipogenesis, at the expense of osteogenesis, through BMP2-mediated increases in the master regulatory gene for adipogenesis, peroxisome proliferator-activated receptor-γ (PPARγ). Inhibiting PPARγ during osteogenesis has been suggested to drive the differentiation of bone marrow stromal/stem cells toward an osteogenic, rather than an adipogenic, lineage. We demonstrate that knocking down PPARγ while concurrently administering BMP2 can reduce adipogenesis, but we found that it also impairs BMP2-induced osteogenesis and leads to bone nonunion in a mouse femoral segmental defect model. In addition, in vitro studies using the mouse bone marrow stromal cell line M2-10B4 and mouse primary bone marrow stromal cells confirmed that PPARγ knockdown inhibits BMP2-induced adipogenesis; attenuates BMP2-induced cell proliferation, migration, invasion, and osteogenesis; and escalates BMP2-induced cell apoptosis. More important, BMP receptor 2 and 1B expression was also significantly inhibited by the combined BMP2 and PPARγ knockdown treatment. These findings indicate that PPARγ is critical for BMP2-mediated osteogenesis during bone repair. Thus, uncoupling BMP2-mediated osteogenesis and adipogenesis using PPARγ inhibition to combat BMP2's adverse effects may not be feasible.

Indexed as

Bone RegenerationFemurOsteogenesisAdipogenesisAnimalsBone Morphogenetic Protein 2Cell LineCell MovementCell ProliferationGene Knockdown TechniquesHumansMaleMiceMice, TransgenicPPAR gammaBMP2 protein, humanBmp2 protein, mouseBone Morphogenetic Protein 2PPAR gammaPparg protein, mouse

Identifiers

PMID30593824
PMCPMC6412314
OpenAlexW2906188290

What OpenQuestion holds

Textmetadata
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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.