Evidence map›Paper›PMID 30970007›Full record

ArticlePloS one2019

Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.

Aaron Dolor, Sara L Sampson, Ann A Lazar, Jeffrey C Lotz, Francis C Szoka, Aaron J Fields

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.8field-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

26 citing papers in PubMed, 52 citations in OpenAlex.

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  12. Changes in Elements and Relationships among Elements in Intervertebral Disc Degeneration.International journal of environmental research and public health · 2022
    Article
  13. The contributions of cartilage endplate composition and vertebral bone marrow fat to intervertebral disc degeneration in patients with chronic low back pain.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2022
    Observational
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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

6 authors at 1 institution in 1 country.

Aaron DolorDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
Sara L SampsonDepartment of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, United States of America.
Ann A LazarDepartment of Preventive and Restorative Dental Sciences, University of California, San Francisco, CA, United States of America.
Jeffrey C LotzDepartment of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, United States of America.
Francis C SzokaDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
Aaron J FieldsDepartment of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, United States of America.ORCID 0000-0001-6460-4506
University of California, San Francisco · US

Funding

Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
UCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOTZ, JEFFREY C. · 2014 to 2018
$3.0M
Role of the cartilage endplate in spinal disc degenerationR01AR070198 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FIELDS, AARON J · 2017 to 2021
$1.7M
NCATS NIH HHS UL1 TR001872NIAMS NIH HHS P30 AR066262NIAMS NIH HHS R01 AR070198NIGMS NIH HHS T32 GM007175
6 · The paper itself

Abstract

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach.

Indexed as

AdultAgedBiological TransportCartilageCell SurvivalCollagenExtracellular MatrixHumansIntervertebral DiscIntervertebral Disc DegenerationIn Vitro TechniquesMatrix Metalloproteinase 8Middle AgedRecombinant ProteinsCollagenMatrix Metalloproteinase 8MMP8 protein, humanRecombinant Proteins

Identifiers

PMID30970007
PMCPMC6457523
OpenAlexW2935847147

What OpenQuestion holds

Textmetadata
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.