Evidence map›Paper›PMID 25003898›Full record

ArticlePloS one2014

EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.

Lin Wan, Fengjie Zhang, Qiling He, Wing Pui Tsang, Li Lu, Qingnan Li, Zhihong Wu, Guixing Qiu, Guangqian Zhou, Chao Wan

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

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  17. Hypoxia-Inducible Factors Signaling in Osteogenesis and Skeletal Repair.International journal of molecular sciences · 2022
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

10 authors at 7 institutions in 2 countries.

Lin WanMinistry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Fengjie ZhangMinistry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Qiling HeDepartments of Microbiology and Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Wing Pui TsangMinistry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Li LuMinistry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, New Drug Function Research Center, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
Qingnan LiGuangdong Key Laboratory of Pharmaceutical Bioactive Substances, New Drug Function Research Center, School of Life Science and Biopharmacy, Guangdong Pharmaceutical University, Guangzhou, China.
Zhihong WuDepartment of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Guixing QiuDepartment of Orthopaedics, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Guangqian ZhouThe Center for Anti-Ageing and Regenerative Medicine, Medical School, Shenzhen University, Shenzhen, China.
Chao WanMinistry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Chinese University of Hong Kong · CNChinese University of Hong Kong, Shenzhen · CNGuangdong Pharmaceutical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNPeking Union Medical College Hospital · CNShenzhen University · CNUniversity of Alabama at Birmingham · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-α (HIF-α) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration.

Indexed as

AnimalsBone RegenerationBony CallusCell DifferentiationCell ProliferationCells, CulturedChondrocytesErythropoietinFemoral FracturesFemurGrowth PlateMetatarsal BonesMice, Inbred C57BLNeovascularization, PhysiologicPrimary Cell CultureProteoglycansErythropoietinProteoglycansReceptors, Erythropoietin

Identifiers

PMID25003898
PMCPMC4087003
OpenAlexW2064367477

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.