Evidence map›Paper›PMID 22264144›Full record

ArticleStem cells and development2012

Additive effects of sonic hedgehog and Nell-1 signaling in osteogenic versus adipogenic differentiation of human adipose-derived stromal cells.

Aaron W James, Shen Pang, Asal Askarinam, Mirko Corselli, Janette N Zara, Raghav Goyal, Le Chang, Angel Pan, Jia Shen, Wei Yuan and 5 more

Abstract read
In one paragraph

Article in Stem cells and development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.2field-weighted citation impact, top 5% 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, 90 citations in OpenAlex.

  1. Review
  2. Boosting Sensory Nerve-to-Bone Interactions Enhances Hedgehog Mediated Calvarial Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Biology · 2025
    Article
  4. Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Signaling network regulating osteogenesis in mesenchymal stem cells.Journal of cell communication and signaling · 2022
    Review
  10. Review
  11. Review
  12. Review
  13. Bioactive Glass: Methods for Assessing Angiogenesis and Osteogenesis.Frontiers in cell and developmental biology · 2021
    Review
  14. Sonic Hedgehog as a Regulator of Endometrial Mesenchymal Stem/Stromal Cell Activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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 2 institutions in 1 country.

Aaron W JamesSection of Orthodontics, Dental and Craniofacial Research Institute, School of Dentistry, University of California, Los Angeles, California, USA.
Shen Pang
Asal Askarinam
Mirko Corselli
Janette N Zara
Raghav Goyal
Le Chang
Angel Pan
Jia Shen
Wei Yuan
David Stoker
Xinli Zhang
John S Adams
Kang Ting
Chia Soo
University of California System · USMarina Del Rey Hospital · US

Funding

UCLA FUNDAMENTAL CLINICAL RESEARCH TRAINING PROGRAMT32DE007296 · NIDCR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WONG, DAVID T · 1996 to 2011
$5.8M
NIDCR NIH HHS 5T32DE007296-14NIDCR NIH HHS R01 DE01607NIDCR NIH HHS R21 DE0177711
6 · The paper itself

Abstract

A theoretical inverse relationship exists between osteogenic (bone forming) and adipogenic (fat forming) mesenchymal stem cell (MSC) differentiation. This inverse relationship in theory partially underlies the clinical entity of osteoporosis, in which marrow MSCs have a preference for adipose differentiation that increases with age. Two pro-osteogenic cytokines have been recently studied that each also possesses antiadipogenic properties: Sonic Hedgehog (SHH) and NELL-1 proteins. In the present study, we assayed the potential additive effects of the biologically active N-terminus of SHH (SHH-N) and NELL-1 protein on osteogenic and adipogenic differentiation of human primary adipose-derived stromal cell (hASCs). We observed that both recombinant SHH-N and NELL-1 protein significantly enhanced osteogenic differentiation and reduced adipose differentiation across all markers examined (alkaline phosphatase, Alizarin red and Oil red O staining, and osteogenic gene expression). Moreover, SHH-N and NELL-1 directed signaling produced additive effects on the pro-osteogenic and antiadipogenic differentiation of hASCs. NELL-1 treatment increased Hedgehog signaling pathway expression; coapplication of the Smoothened antagonist Cyclopamine reversed the pro-osteogenic effect of NELL-1. In summary, Hedgehog and Nell-1 signaling exert additive effects on the pro-osteogenic and antiadipogenic differentiation of ASCs. These studies suggest that the combination cytokines SHH-N+NELL-1 may represent a viable future technique for inducing the osteogenic differentiation of MSCs.

Indexed as

AdipogenesisOsteogenesisAdipose TissueAdultAdult Stem CellsAlkaline PhosphataseAntigens, DifferentiationCalcium-Binding ProteinsCells, CulturedCore Binding Factor Alpha 1 SubunitFemaleHedgehog ProteinsHumansMaleMesenchymal Stem CellsMiddle AgedAlkaline PhosphataseAntigens, DifferentiationCalcium-Binding ProteinsCore Binding Factor Alpha 1 SubunitcyclopamineHedgehog ProteinsNELL1 protein, humanNerve Tissue ProteinsReceptors, G-Protein-CoupledRUNX2 protein, humanSHH protein, humanSmoothened ReceptorSMO protein, humanVeratrum Alkaloids

Identifiers

PMID22264144
PMCPMC3411358
OpenAlexW2058587173

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.