Evidence map›Paper›PMID 29905970›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2018

Neurexin Superfamily Cell Membrane Receptor Contactin-Associated Protein Like-4 (Cntnap4) Is Involved in Neural EGFL-Like 1 (Nell-1)-Responsive Osteogenesis.

Chenshuang Li, Zhong Zheng, Pin Ha, Xiaoyan Chen, Wenlu Jiang, Shan Sun, Feng Chen, Greg Asatrian, Emily A Berthiaume, Jong Kil Kim and 5 more

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

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

21 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. NELL-1: role and mechanisms in disease pathogenesis and development.Frontiers in cell and developmental biology · 2026
    Review
  3. Article
  4. Article
  5. Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
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  11. Article
  12. Review
  13. Review
  14. Signaling network regulating osteogenesis in mesenchymal stem cells.Journal of cell communication and signaling · 2022
    Review
  15. Norrie disease protein is essential for cochlear hair cell maturation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
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 5 institutions in 3 countries.

Chenshuang LiDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Zhong ZhengDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Pin HaDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Xiaoyan ChenDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Wenlu JiangDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Shan SunDepartment of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing, PR China.
Feng ChenSchool and Hospital of Stomatology, Peking University, Beijing, PR China.
Greg AsatrianDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Emily A BerthiaumeDavid Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jong Kil KimDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Eric C ChenDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Shen PangDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Xinli ZhangDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Kang TingDivision of Growth and Development, Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.
Chia SooDivision of Plastic and Reconstructive Surgery and Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, CA, USA.
University of California, Los Angeles · USOrthopaedic Hospital · USPeking University · CNPharmaceutical Biotechnology (Czechia) · CZZhejiang University · CN

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
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
NCATS NIH HHS UL1 TR001881NIAMS NIH HHS R01 AR061399NIAMS NIH HHS R01 AR066782NIAMS NIH HHS R01 AR068835
6 · The paper itself

Abstract

Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system. Meanwhile, secretory protein neural EGFL-like 1 (Nell-1) is known to exert potent osteogenic effects in multiple small and large animal models without the off-target effects commonly found with bone morphogenetic protein 2. In this study, while searching for a Nell-1-specific cell surface receptor during osteogenesis, we identified and validated a ligand/receptor-like interaction between Nell-1 and Cntnap4 by demonstrating: 1) Nell-1 and Cntnap4 colocalization on the surface of osteogenic-committed cells; 2) high-affinity interaction between Nell-1 and Cntnap4; 3) abrogation of Nell-1-responsive Wnt and MAPK signaling transduction, as well as osteogenic effects, via Cntnap4 knockdown; and 4) replication of calvarial cleidocranial dysplasias-like defects observed in Nell-1-deficient mice in Wnt1-Cre-mediated Cntnap4-knockout transgenic mice. In aggregate, these findings indicate that Cntnap4 plays a critical role in Nell-1-responsive osteogenesis. Further, this is the first functional annotation for Cntnap4 in the musculoskeletal system. Intriguingly, Nell-1 and Cntnap4 also colocalize on the surface of human hippocampal interneurons, implicating Nell-1 as a potential novel ligand for Cntnap4 in the nervous system. This unexpected characterization of the ligand/receptor-like interaction between Nell-1 and Cntnap4 indicates a novel biological functional axis for Nell-1 and Cntnap4 in osteogenesis and, potentially, in neural development and function. © 2018 American Society for Bone and Mineral Research.

Indexed as

OsteogenesisAmino Acid SequenceAnimalsAnimals, NewbornBacteriophage T7Bone MarrowCalcium-Binding ProteinsCell LineCell LineageCell MembraneGene DeletionGlycoproteinsHumansIntegrasesMembrane ProteinsMice, Inbred C57BLCalcium-Binding ProteinsCntnap4 protein, mouseCre recombinaseGlycoproteinsIntegrasesMembrane ProteinsNell1 protein, mouseNerve Tissue ProteinsCONTACTIN-ASSOCIATED PROTEIN-LIKE 4 (CNTNAP4)LIGAND/RECEPTOR-LIKE INTERACTIONNELL-1/CNTNAP4 AXISNEURAL EGFL-LIKE 1 (NELL-1)OSTEOGENESIS

Identifiers

PMID29905970
PMCPMC6390490
OpenAlexW2808190676

What OpenQuestion holds

Textmetadata
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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.