Evidence map›Paper›PMID 21611965›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2011

Nfatc2 is a primary response gene of Nell-1 regulating chondrogenesis in ATDC5 cells.

Weiwei Chen, Xinli Zhang, Ronald K Siu, Feng Chen, Jia Shen, Janette N Zara, Cymbeline T Culiat, Sotirios Tetradis, Kang Ting, Chia Soo

Open access · bronzeAbstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

23 citing papers in PubMed, 42 citations in OpenAlex.

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  4. Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025
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  8. [Metformin and lipopolysaccharide regulate transcription ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022
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  12. Neurexin Superfamily Cell Membrane Receptor Contactin-Associated Protein Like-4 (Cntnap4) Is Involved in Neural EGFL-Like 1 (Nell-1)-Responsive Osteogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018
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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

10 authors at 3 institutions in 2 countries.

Weiwei ChenZhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Xinli Zhang
Ronald K Siu
Feng Chen
Jia Shen
Janette N Zara
Cymbeline T Culiat
Sotirios Tetradis
Kang Ting
Chia Soo
University of California, Los Angeles · USOak Ridge National Laboratory · USZhejiang University · CN

Funding

UCLA FUNDAMENTAL CLINICAL RESEARCH TRAINING PROGRAMT32DE007296 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WONG, DAVID T · 1996 to 2011
$5.8M
NELL-1, A Cbfa1 DOWNSTREAM TARGET, IN BONE FORMATIONR01DE016107 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TING, KANG · 2004 to 2009
$2.1M
NIDCR NIH HHS R01-DE01607NIDCR NIH HHS R01 DE016107NIDCR NIH HHS R21-DE0177711NIDCR NIH HHS T32 DE007296NIDCR NIH HHS T32-DE007296
6 · The paper itself

Abstract

Nell-1 is a growth factor required for normal skeletal development and expression of extracellular matrix proteins required for bone and cartilage cell differentiation. We identified the transcription factor nuclear factor of activated T cells (Nfatc2) as a primary response gene of Nell-1 through a microarray screen, with validation using real-time polymerase chain reaction (PCR). We investigated the effects of recombinant Nell-1 protein on the chondrogenic cell line ATDC5 and primary mouse chondrocytes. The osteochondral transcription factor Runx2 was investigated as a possible intermediary between Nell-1 and Nfatc2 using adenoviral overexpression of wild-type and dominant-negative Runx2. Nell-1 transiently induced both transcription and translation of Nfatc2, an effect inhibited by transduction of dominant-negative Runx2, suggesting that Runx2 was necessary for Nfatc2 induction. Differentiation assays revealed inhibitory effects of Nell-1 on ATDC5 cells. Although proliferation was unaffected, expression of chondrocyte-specific genes was decreased, and cartilage nodule formation and proteoglycan accumulation were suppressed. siRNA knockdown of Nfatc2 significantly reversed these inhibitory effects. To elucidate the relationship between Nell-1, Runx2, and Nfatc2 in vivo, their presence and distribution were visualized in femurs of wild-type and Nell1-deficient mice at both neonatal and various developmental stages using immunohistochemistry. All three proteins colocalized in the perichondrium of wild-type femurs but stained weakly or were completely absent in Nell1-deficient femurs at neonatal stages. Thus Nfatc2 likely plays an important role in Nell-1-mediated osteochondral differentiation in vitro and in vivo. To our knowledge, this is the first demonstration that Nfatc2 is a primary response gene of Nell-1.

Indexed as

AnimalsCalcium-Binding ProteinsCell DifferentiationCell LineChondrocytesChondrogenesisCore Binding Factor Alpha 1 SubunitFemurGene Expression RegulationGlycoproteinsHumansImmunohistochemistryMiceNerve Tissue ProteinsNFATC Transcription FactorsOligonucleotide Array Sequence AnalysisCalcium-Binding ProteinsCore Binding Factor Alpha 1 SubunitGlycoproteinsNELL1 protein, humanNell1 protein, mouseNerve Tissue ProteinsNfatc2 protein, mouseNFATC Transcription FactorsRNA, MessengerRNA, Small Interfering

Identifiers

PMID21611965
PMCPMC3312756
OpenAlexW1965336059

What OpenQuestion holds

Textmetadata
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.