Evidence map›Paper›PMID 30643142›Full record

ArticleNature communications2019

Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis.

Hao Chen, Bo Hu, Xiao Lv, Shouan Zhu, Gehua Zhen, Mei Wan, Amit Jain, Bo Gao, Yu Chai, Mi Yang and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
206citing papers in PubMed, 1 pooled it
18.7field-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

206 citing papers in PubMed, 1 synthesis or guideline pooled it, 292 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Piezo2FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  9. Review
  10. Article
  11. Review
  12. Hypothalamic prolactin receptorNature communications · 2026
    Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. SCD1 Regulates Osteoclast Differentiation by Modulating Arachidonic Acid Metabolism and Mitochondrial Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 2 countries.

Hao ChenDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Bo HuDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Xiao LvDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Shouan ZhuDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Gehua ZhenDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Mei WanDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Amit JainDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Bo GaoDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Yu ChaiDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Mi YangDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Xiao WangDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0001-6395-706X
Ruoxian DengDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Lei WangDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Yong CaoDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Shuangfei NiDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Shen LiuDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA.
Wen YuanSection of Spine Surgery, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
Huajiang ChenSection of Spine Surgery, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200433, P. R. China.
Xinzhong DongHoward Hughes Medical Institute and The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.ORCID http://orcid.org/0000-0002-9750-7718
Yun GuanDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Huilin YangDepartment of Orthopaedic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, P. R. China. suzhouspine@163.com.
Xu CaoDepartment of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, MD, 21205, USA. xcao11@jhmi.edu.
Johns Hopkins University · USHoward Hughes Medical Institute · USSecond Military Medical University · CNSoochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.

Indexed as

Adrenergic beta-AntagonistsAdrenergic FibersAnimalsBone and BonesBone DensityBone RegenerationCells, CulturedCyclooxygenase 2DinoprostoneDisease Models, AnimalFeedback, PhysiologicalFemaleHumansHydroxyprostaglandin DehydrogenasesMaleMice15-hydroxyprostaglandin dehydrogenaseAdrenergic beta-AntagonistsCyclooxygenase 2DinoprostoneHydroxyprostaglandin DehydrogenasesPropranololPtger4 protein, mousePtgs2 protein, mousePyridinesReceptors, Prostaglandin E, EP4 SubtypeSW033291Thiophenes

Identifiers

PMID30643142
PMCPMC6331599
OpenAlexW2909717083

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.