Evidence map›Paper›PMID 33441426›Full record

ArticleScience translational medicine2021

Targeting cartilage EGFR pathway for osteoarthritis treatment.

Yulong Wei, Lijun Luo, Tao Gui, Feifan Yu, Lesan Yan, Lutian Yao, Leilei Zhong, Wei Yu, Biao Han, Jay M Patel and 11 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
22.1field-weighted citation impact, top 1% 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

96 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Article
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  8. Article
  9. Targeting the SARM1-cADPR-CaArthritis research & therapy · 2026
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  14. Targeted Inhibition of CD74Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 3 countries.

Yulong WeiDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-3823-9984
Lijun LuoDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tao GuiDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-1892-4001
Feifan YuAlphathera LLC, Philadelphia, PA 19146, USA.
Lesan YanDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-3616-9628
Lutian YaoDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-0652-2075
Leilei ZhongDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wei YuDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-6705-8264
Biao HanSchool of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.ORCID 0000-0002-7812-3524
Jay M PatelDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-4889-0818
Jessica F LiuDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-2663-8438
Frank BeierDepartment of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.ORCID 0000-0002-8505-7537
Lawrence Scott LevinDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-9108-5182
Charles NelsonDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-9945-0188
Zengwu ShaoDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Lin HanSchool of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.ORCID 0000-0003-4180-1288
Robert L MauckDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Andrew TsourkasDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jaimo AhnDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-8151-9987
Zhiliang ChengDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA. qinling@pennmedicine.upenn.edu zcheng@seas.upenn.edu.ORCID 0000-0003-3351-6874
Ling QinDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. qinling@pennmedicine.upenn.edu zcheng@seas.upenn.edu.ORCID 0000-0002-2582-0078
University of Pennsylvania · USUnion Hospital · CNDrexel University · USPhiladelphia VA Medical Center · USAlphaThera (United States) · USUniversity of Michigan · USWestern University · CA

Funding

Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)P30AR069619 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI LOUIS J SOSLOWSKY · 2016 to 2026
$9.1M
Biomechanics of Cartilage: Roles of Decorin in ECM Assembly and DegradationR01AR074490 · NIAMS · DREXEL UNIVERSITY · PI Lin Han · 2019 to 2026
$2.3M
EGFR signaling in osteoarthritis and treatmentR01AG067698 · NIA · UNIVERSITY OF PENNSYLVANIA · PI QIN, LING · 2020 to 2024
$2.3M
Mechanism of radiotherapy-induced osteoporosis and its treatmentR01AR066098 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI QIN, LING · 2015 to 2019
$1.8M
Role of EGFR signaling in bone formation and the anabolic actions of PTHR01DK095803 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI QIN, LING · 2013 to 2017
$1.7M
Targeted treatment for radiculopathy via engineered PLA2-responsive multifunctional micellesR01NS100892 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI CHENG, ZHILIANG · 2017 to 2021
$1.7M
NIAMS NIH HHS P30 AR069619NIAMS NIH HHS R01 AR066098NIAMS NIH HHS R01 AR074490NIA NIH HHS R01 AG067698NIDDK NIH HHS R01 DK095803NINDS NIH HHS R01 NS100892
6 · The paper itself

Abstract

Osteoarthritis (OA) is a widespread joint disease for which there are no disease-modifying treatments. Previously, we found that mice with cartilage-specific epidermal growth factor receptor (EGFR) deficiency developed accelerated knee OA. To test whether the EGFR pathway can be targeted as a potential OA therapy, we constructed two cartilage-specific EGFR overactivation models in mice by overexpressing heparin binding EGF-like growth factor (HBEGF), an EGFR ligand. Compared to wild type, Col2-Cre HBEGF-overexpressing mice had persistently enlarged articular cartilage from adolescence, due to an expanded pool of chondroprogenitors with elevated proliferation ability, survival rate, and lubricant production. Adult Col2-Cre HBEGF-overexpressing mice and Aggrecan-CreER HBEGF-overexpressing mice were resistant to cartilage degeneration and other signs of OA after surgical destabilization of the medial meniscus (DMM). Treating mice with gefitinib, an EGFR inhibitor, abolished the protective action against OA in HBEGF-overexpressing mice. Polymeric micellar nanoparticles (NPs) conjugated with transforming growth factor-α (TGFα), a potent EGFR ligand, were stable and nontoxic and had long joint retention, high cartilage uptake, and penetration capabilities. Intra-articular delivery of TGFα-NPs effectively attenuated surgery-induced OA cartilage degeneration, subchondral bone plate sclerosis, and joint pain. Genetic or pharmacologic activation of EGFR revealed no obvious side effects in knee joints and major vital organs in mice. Together, our studies demonstrate the feasibility of using nanotechnology to target EGFR signaling for OA treatment.

Indexed as

Cartilage, ArticularOsteoarthritisAnimalsDisease Models, AnimalErbB ReceptorsKnee JointMiceErbB Receptors

Identifiers

PMID33441426
PMCPMC8027922
OpenAlexW3119762793

What OpenQuestion holds

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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.