Evidence map›Paper›PMID 34337335›Full record

ArticleJOR spine2021

Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section.

Alon Lai, Jennifer Gansau, Sarah E Gullbrand, James Crowley, Carla Cunha, Stefan Dudli, Julie B Engiles, Marion Fusellier, Raquel M Goncalves, Daisuke Nakashima and 9 more

Open access · goldAbstract read
In one paragraph

Article in JOR spine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
9.9field-weighted citation impact, top 1% 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

78 citing papers in PubMed, 102 citations in OpenAlex.

  1. Persistent ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  3. Article
  4. Article
  5. Article
  6. IntradiscalJOR spine · 2026
    Article
  7. Deletion of aJOR spine · 2026
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Intervertebral disc degeneration.Nature reviews. Disease primers · 2026
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. IMID-284: a potent pyruvate kinase M2 inhibitor with dual anti-inflammatory and analgesic effects in intervertebral disc disease.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 · 2025
    Article

18 more citing papers are in PubMed but not listed here.

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

19 authors at 13 institutions in 7 countries.

Alon LaiLeni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.ORCID https://orcid.org/0000-0002-0163-4588
Jennifer GansauLeni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.
Sarah E GullbrandMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA.ORCID https://orcid.org/0000-0001-7806-6606
James CrowleySurgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School University of New South Wales Sydney Australia.
Carla Cunhai3S-Instituto de Investigação e InovaçãoemSaúde Universidade do Porto Porto Portugal.
Stefan DudliUniversity Clinic of Rheumatology, Center of Experimental Rheumatology Balgrist University Hospital, University of Zurich Zurich Switzerland.
Julie B EngilesDepartment of Pathobiology, New Bolton Center, School of Veterinary Medicine University of Pennsylvania Kennett Square Pennsylvania USA.
Marion FusellierRegenerative Medicine and Skeleton, Inserm, UMR 1229, RMeS Université de Nantes, ONIRIS Nantes Cedex France.
Raquel M Goncalvesi3S-Instituto de Investigação e InovaçãoemSaúde Universidade do Porto Porto Portugal.
Daisuke NakashimaDepartment of Orthopaedic Surgery Keio University School of Medicine Tokyo Japan.ORCID https://orcid.org/0000-0003-1105-2669
Jeffrey OkewunmiLeni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.
Matthew PelletierSurgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School University of New South Wales Sydney Australia.ORCID https://orcid.org/0000-0003-1643-6696
Steven M PresciuttiDepartment of Orthopaedic Surgery Emory University Atlanta Georgia USA.ORCID https://orcid.org/0000-0001-6547-9495
Jordy ScholDepartment of Orthopaedic Surgery, Surgical Science Tokai University School of Medicine Isehara Japan.
Yoshiki TakeokaDepartment of Orthopaedic Surgery Brigham and Women's Hospital Boston Massachusetts USA.
Sidong YangDepartment of Spinal Surgery The Third Hospital of Hebei Medical University Shijiazhuang China.ORCID https://orcid.org/0000-0003-2342-4714
Takashi YurubeDepartment of Orthopaedic Surgery Kobe University Graduate School of Medicine Kobe Japan.ORCID https://orcid.org/0000-0002-3007-361X
Yejia ZhangMcKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA.ORCID https://orcid.org/0000-0002-7484-8800
James C IatridisLeni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.ORCID https://orcid.org/0000-0002-2186-0590
Icahn School of Medicine at Mount Sinai · USUniversity of Pennsylvania · USUNSW Sydney · AUBrigham and Women's Hospital · USEmory University · USHebei Medical University · CNi3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto · PTInserm · FRKeio University · JPKobe University · JPTokai University · JPUniversidade do Porto · PTUniversity of Zurich · CH

Funding

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
Mechanisms for Regenerative Healing in Intervertebral DiscsR01AR080096 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI James C. Iatridis · 2022 to 2026
$3.8M
Role of TNFalpha in discogenic pain progression and as a treatment targetR01AR078857 · NIAMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI James C. Iatridis · 2022 to 2026
$3.2M
NIAMS NIH HHS R01 AR057397NIAMS NIH HHS R01 AR078857NIAMS NIH HHS R01 AR080096
6 · The paper itself

Abstract

backgroundRats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions.

aimsThis study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. MATERIALS &

methodsThis study involved a literature review, a survey of experts in the field, and a validation study using 25 slides that were scored by 15 graders from different international institutes to determine inter- and intra-rater reliability.

resultsA new IVD degeneration grading system was established and it consists of eight significant degenerative features, including nucleus pulposus (NP) shape, NP area, NP cell number, NP cell morphology, annulus fibrosus (AF) lamellar organization, AF tears/fissures/disruptions, NP-AF border appearance, as well as endplate disruptions/microfractures and osteophyte/ossification. The validation study indicated this system was easily adopted, and able to discern different severities of degenerative changes from different rat IVD degeneration models with high reproducibility for both experienced and inexperienced graders. In addition, a widely-accepted protocol for histological preparation of rat IVD samples based on the survey findings include paraffin embedding, sagittal orientation, section thickness < 10 μm, and staining using H&E and/or SO/FG to facilitate comparison across laboratories.

conclusionThe proposed histological preparation protocol and grading system provide a platform for more precise comparisons and more robust evaluation of rat IVD degeneration models and interventions across laboratories.

Indexed as

histologyhistology grading scalehistopathologyintervertebral disc degenerationintervertebral disc regenerationrat model

Identifiers

PMID34337335
PMCPMC8313153
OpenAlexW3165199523

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.