Evidence map›Paper›PMID 31419488›Full record

ArticleOsteoarthritis and cartilage2019

Multiscale and multimodal structure-function analysis of intervertebral disc degeneration in a rabbit model.

B G Ashinsky, S E Gullbrand, E D Bonnevie, S A Mandalapu, C Wang, D M Elliott, L Han, R L Mauck, H E Smith

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Osteoarthritis and cartilage, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
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

27 citing papers in PubMed.

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  20. ISSLS Prize in Bioengineering Science 2022: low rate cyclic loading as a therapeutic strategy for intervertebral disc regeneration.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
    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

9 authors.

B G AshinskyDepartment of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. Electronic address: beth.ashinsky@gmail.com.
S E GullbrandDepartment of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. Electronic address: sgullb@pennmedicine.upenn.edu.
E D BonnevieDepartment of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. Electronic address: edbon@pennmedicine.upenn.edu.
S A MandalapuDepartment of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. Electronic address: sai.mandalapu@pennmedicine.upenn.edu.
C WangSchool of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA. Electronic address: cw583@drexel.edu.
D M ElliottDepartment of Biomedical Engineering, University of Delaware, Newark, DE, USA. Electronic address: delliott@udel.edu.
L HanSchool of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA. Electronic address: lh535@drexel.edu.
R L MauckDepartment of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. Electronic address: lemauck@pennmedicine.upenn.edu.
H E SmithDepartment of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA. Electronic address: harvey.smith@uphs.upenn.edu.

Funding

Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)P30AR069619 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI LOUIS J SOSLOWSKY · 2016 to 2026
$9.1M
Multiscale and Multimodal Structure-Function Analysis of Intervertebral Interfaces During Degeneration and RegenerationF30AG060670 · NIA · DREXEL UNIVERSITY · PI ASHINSKY, BETH GAYLE · 2018 to 2021
$193k
Altered Mechanical Signaling in the Annulus Fibrosus in Intervertebral Disc DegenerationF32AR072478 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BONNEVIE, EDWARD D · 2018 to 2019
$120k
Tissue-Engineered Constructs for Treatment of Intervertebral Disc DegenerationIK2RX001476 · VA · PHILADELPHIA VA MEDICAL CENTER · PI SMITH, HARVEY E. · 2015 to 2020
–
Tissue Engineered Total Disc Replacement in a Large Animal ModelI01RX002274 · VA · PHILADELPHIA VA MEDICAL CENTER · PI MAUCK, ROBERT L, SMITH, HARVEY E. · 2017 to 2025
–
Bioactive Injectable Implants for Functional Intervertebral Disc RegenerationI01RX001321 · VA · PHILADELPHIA VA MEDICAL CENTER · PI Robert L Mauck, Lachlan James Smith · 2014 to 2026
–
The Role of the Endplate in Intervertebral Disc Degeneration and RegenerationIK1RX002445 · VA · PHILADELPHIA VA MEDICAL CENTER · PI GULLBRAND, SARAH E · 2018 to 2019
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NIAMS NIH HHS F32 AR072478NIAMS NIH HHS P30 AR069619NIA NIH HHS F30 AG060670RRD VA I01 RX001321RRD VA I01 RX002274RRD VA I21 RX003289RRD VA IK1 RX002445RRD VA IK2 RX001476
6 · The paper itself

Abstract

objectivesThe objective of this study was to perform a quantitative analysis of the structural and functional alterations in the intervertebral disc during in vivo degeneration, using emerging tools that enable rigorous assessment from the microscale to the macroscale, as well as to correlate these outcomes with noninvasive, clinically relevant imaging parameters.

designDegeneration was induced in a rabbit model by puncturing the annulus fibrosus (AF) with a 16-gauge needle. 2, 4, 8, and 12 weeks following puncture, degenerative changes in the discs were evaluated via magnetic resonance imaging (MRI), whole motion segment biomechanics, atomic force microscopy, histology and polarized light microscopy, immunohistochemistry, biochemical content, and second harmonic generation imaging.

resultsFollowing puncture, degeneration was evident through marked changes in whole disc structure and mechanics. Puncture acutely compromised disc macro and microscale mechanics, followed by progressive stiffening and remodeling. Histological analysis showed substantial anterior fibrotic remodeling and osteophyte formation, as well as an overall reduction in disc height, and disorganization and infolding of the AF lamellae into the NP space. Increases in NP collagen content and aggrecan breakdown products were also noted within 4 weeks. On MRI, NP T2 was reduced at all post-puncture time points and correlated significantly with microscale indentation modulus.

conclusionThis study defined the time dependent changes in disc structure-function relationships during IVD degeneration in a rabbit annular injury model and correlated degeneration severity with clinical imaging parameters. Our findings identified AF infolding and occupancy of the space as a principle mechanism of disc degeneration in response to needle puncture, and provide new insights to direct the development of novel therapeutics.

Indexed as

AggrecansAnimalsAnnulus FibrosusBiomechanical PhenomenaCollagenDisease Models, AnimalDisease ProgressionImmunohistochemistryIntervertebral DiscIntervertebral Disc DegenerationMagnetic Resonance ImagingMicroscopy, Atomic ForceMicroscopy, PolarizationNucleus PulposusPuncturesRabbitsAggrecansCollagenAnimal modelAtomic force microscopyIntervertebral disc degenerationMagnetic resonance imaging

Identifiers

PMID31419488
PMCPMC6875634

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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.