Evidence map›Paper›PMID 25534363›Full record

ArticleOsteoarthritis and cartilage2015

Soluble factors from the notochordal-rich intervertebral disc inhibit endothelial cell invasion and vessel formation in the presence and absence of pro-inflammatory cytokines.

M C Cornejo, S K Cho, C Giannarelli, J C Iatridis, D Purmessur

Open access · bronzeAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

49 citing papers in PubMed, 84 citations in OpenAlex.

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  17. Frontiers in pain research (Lausanne, Switzerland) · 2022
    Review
  18. Review
  19. Cartilage · 2021
    Article
  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

5 authors at 2 institutions in 1 country.

M C CornejoLeni and Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: Marisa.cornejo@mountsinai.org.
S K ChoLeni and Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: Samuel.cho@mountsinai.org.
C GiannarelliCardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: Chiara.giannarelli@mssm.edu.
J C IatridisLeni and Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: James.iatridis@mssm.edu.
D PurmessurLeni and Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: Devina.purmessur@mssm.edu.
Icahn School of Medicine at Mount Sinai · USCardiovascular Institute of the South · US

Funding

TRAINING PROGRAM IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007824 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELB, BRUCE D · 1995 to 2022
$8.6M
Model of Human Disc Regeneration in the spectrum of Degenerative Disc DiseaseR01AR057397 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI IATRIDIS, JAMES C. · 2011 to 2021
$5.1M
Notochordal Cell Derived Therapies for Painful Disc DegenerationR01AR064157 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI IATRIDIS, JAMES C. · 2013 to 2017
$2.7M
Mechanical Injury and Repair in the Intervertebral DiscR01AR051146 · NIAMS · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI IATRIDIS, JAMES C. · 2005 to 2013
$2.6M
Role of alternatively spliced Tissue Factor in atherosclerosisK23HL111339 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GIANNARELLI, CHIARA · 2013 to 2017
$782k
Functional Notochordal Cell Interactions to Prevent and Repair Disc DegenerationR21AR056037 · NIAMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI IATRIDIS, JAMES C. · 2009 to 2010
$386k
NHLBI NIH HHS K23 HL111339NHLBI NIH HHS T32 HL007824NIAMS NIH HHS R01 AR051146NIAMS NIH HHS R01 AR057397NIAMS NIH HHS R01 AR064157NIAMS NIH HHS R21 AR056037
6 · The paper itself

Abstract

backgroundChronic low back pain can be associated with the pathological ingrowth of blood vessels and nerves into intervertebral discs (IVDs). The notochord patterns the IVD during development and is a source of anti-angiogenic soluble factors such as Noggin and Chondroitin sulfate (CS). These factors may form the basis for a new minimally invasive strategy to target angiogenesis in the IVD.

objectiveTo examine the anti-angiogenic potential of soluble factors from notochordal cells (NCs) and candidates Noggin and CS under healthy culture conditions and in the presence of pro-inflammatory mediators.

designNC conditioned media (NCCM) was generated from porcine NC-rich nucleus pulposus tissue. To assess the effects of NCCM, CS and Noggin on angiogenesis, cell invasion and tubular formation assays were performed using human umbilical vein endothelial cells (HUVECs) ± tumor necrosis factor alpha (TNFα [10 ng/ml]). vascular endothelial growth factor (VEGF)-A, MMP-7, interleukin-6 (IL-6) and IL-8 mRNA levels were assessed using qRT-PCR.

resultsNCCM (10 & 100%), CS (10 and 100 μg) and Noggin (10 and 100 ng) significantly decreased cell invasion of HUVECs with and without TNFα. NCCM 10% and Noggin 10 ng inhibited tubular formation with and without TNFα and CS 100 μg inhibited tubules in Basal conditions whereas CS 10 μg inhibited tubules with TNFα. NCCM significantly decreased VEGF-A, MMP-7 and IL-6 mRNA levels in HUVECs with and without TNFα. CS and Noggin had no effects on gene expression.

conclusionsWe provide the first evidence that soluble factors from NCs can inhibit angiogenesis by suppressing VEGF signaling. Notochordal-derived ligands are a promising minimally invasive strategy targeting neurovascular ingrowth and pain in the degenerated IVD.

Indexed as

Angiogenesis InhibitorsAnimalsCarrier ProteinsChondroitin SulfatesCytokinesHuman Umbilical Vein Endothelial CellsInterleukin-6Interleukin-8Intervertebral DiscMatrix Metalloproteinase 7Neovascularization, PathologicNoggin ProteinNotochordRNA, MessengerSwineTumor Necrosis Factor-alphaAngiogenesis InhibitorsCarrier ProteinsChondroitin SulfatesCXCL8 protein, humanCytokinesIL6 protein, humanInterleukin-6Interleukin-8Matrix Metalloproteinase 7MMP7 protein, humanNoggin ProteinRNA, MessengerTumor Necrosis Factor-alphaVascular Endothelial Growth Factor AVEGFA protein, humanAngiogenesisBack painIntervertebral discNotochordal cellsTNFα

Identifiers

PMID25534363
PMCPMC4411226
OpenAlexW2165465200

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Registered trials

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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.