Evidence map›Paper›PMID 41489839›Full record

ArticleEuropean spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society2026

ISSLS Prize in Basic Science 2026: Early markers of mechanical modulation in whole bovine intervertebral discs loaded in a multiaxial bioreactor.

Barbora Kubincova, Marcia Muerner, Junxuan Ma, Jeannine Mueller, Amra Šećerović, Mazda Farshad, Sibylle Grad

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In one paragraph

Article in 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, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Barbora KubincovaAO Research Institute Davos, Davos Platz, Switzerland.
Marcia MuernerAO Research Institute Davos, Davos Platz, Switzerland.
Junxuan MaAO Research Institute Davos, Davos Platz, Switzerland.
Jeannine MuellerAO Research Institute Davos, Davos Platz, Switzerland.
Amra ŠećerovićAO Research Institute Davos, Davos Platz, Switzerland.
Mazda FarshadUniversity of Zurich, Zurich, Switzerland.
Sibylle GradAO Research Institute Davos, Davos Platz, Switzerland. sibylle.grad@aofoundation.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIntervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP), with mechanical overloading recognized as a driver of disc pathology. This study investigated early responses of bovine caudal intervertebral discs (IVDs) to repetitive multiaxial loading and assessed effects on nociceptive sensitization.

methodsWhole IVDs were cultured ex vivo for 3 or 7 days either free-swelling or under multiaxial loading (0.2 MPa compression, 0-6° flexion, 0-4° torsion, 0.2 Hz, 4 h/day). Disc height, biomechanics, gene expression, biochemical markers, collagen integrity, and cell viability were evaluated. Conditioned medium (CM) from IVDs was applied to primary dorsal root ganglion (DRG) neurons to assess calcium responses and neurite outgrowth.

resultsMultiaxial loading induced rapid, region-specific molecular changes, particularly in the outer annulus fibrosus, with upregulation of inflammatory (IL6) and catabolic (MMP13) genes and mild increases in glycosaminoglycan and nitric oxide release. DRG neurons exposed to CM from loaded IVDs exhibited enhanced capsaicin-evoked calcium responses and increased neurite branching, especially in CGRP-positive nociceptors, indicating early discogenic sensitization. Collagen denaturation showed a trend toward higher levels in loaded IVDs, while cell viability, tissue structure, and biomechanical properties remained preserved.

conclusionMultiaxial loading at the selected magnitude induced early molecular signs of degeneration and neuronal sensitization without detectable alterations in cell viability, tissue structure, or biomechanics, contributing to our understanding of mechanically induced impact on the IVD. Ex vivo multiaxial loading in bioreactors provides a physiologically relevant platform to study the initiation and progression of IVDD and associated discogenic pain mechanisms.

Indexed as

BioreactorsIntervertebral DiscIntervertebral Disc DegenerationAnimalsAwards and PrizesBiomarkersBiomechanical PhenomenaCattleGanglia, SpinalStress, MechanicalWeight-BearingBiomarkersBioreactorDisc degenerationMultiaxialNeurosensitizationOrgan culture

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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.