Evidence map›Paper›PMID 26082355›Full record

ArticleNature communications2015

NELL-1 in the treatment of osteoporotic bone loss.

Aaron W James, Jia Shen, Xinli Zhang, Greg Asatrian, Raghav Goyal, Jin H Kwak, Lin Jiang, Benjamin Bengs, Cymbeline T Culiat, A Simon Turner and 6 more

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

Article in Nature communications, 2015. 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 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
6.3field-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

73 citing papers in PubMed, 144 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. NELL-1: role and mechanisms in disease pathogenesis and development.Frontiers in cell and developmental biology · 2026
    Review
  5. Review
  6. Article
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  8. Review
  9. Review
  10. Article
  11. Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
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  18. Article
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  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 1 country.

Aaron W JamesDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
Jia ShenDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
Xinli ZhangDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, California 90095, USA.
Greg AsatrianDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, California 90095, USA.
Raghav GoyalDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, California 90095, USA.
Jin H KwakDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, California 90095, USA.
Lin JiangDepartment of Neurology, Easton Center for Alzheimer's Disease Research, Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
Benjamin BengsDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
Cymbeline T CuliatOak Ridge National Laboratory (ORNL), Oak Ridge, Tennessee 37830, USA.
A Simon TurnerDepartment of Veterinary Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
Howard B Seim IiiDepartment of Veterinary Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
Benjamin M WuDepartment of Bioengineering and Department of Material Sciences, University of California, Los Angeles, California 90095, USA.
Karen LyonsDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
John S AdamsDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
Kang TingDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
Chia SooDepartment of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, UCLA and Orthopaedic Hospital, University of California, Los Angeles, California 90095, USA.
University of California, Los Angeles · USColorado State University · USOrthopaedic Hospital · USFoundation for Psychocultural Research · USOak Ridge National Laboratory · US

Funding

UCLA FUNDAMENTAL CLINICAL RESEARCH TRAINING PROGRAMT32DE007296 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WONG, DAVID T · 1996 to 2011
$5.8M
VITAMIN D RESISTANCE: MONKEY TO MANR01AR037399 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ADAMS, JOHN S · 1988 to 2013
$4.3M
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
NIAMS NIH HHS R01 AR037399NIAMS NIH HHS R01 AR061399NIAMS NIH HHS R01 AR061399-01A1NIAMS NIH HHS R01 AR066782NIAMS NIH HHS R01AR066782-01NIDCR NIH HHS 5T32DE007296-14NIDCR NIH HHS T32 DE007296
6 · The paper itself

Abstract

NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss.

Indexed as

AdultAgedAged, 80 and overAnimalsbeta CateninBone and BonesCalcium-Binding ProteinsCells, CulturedDrug Evaluation, PreclinicalFemaleHaploinsufficiencyHumansIntegrin beta ChainsMaleMiceMiddle Agedbeta CateninCalcium-Binding ProteinsIntegrin beta ChainsNELL1 protein, humanNerve Tissue ProteinsWnt Proteins

Identifiers

PMID26082355
PMCPMC4557288
OpenAlexW2273202157

What OpenQuestion holds

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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.