Evidence map›Paper›PMID 33863359›Full record

ArticleArthritis research & therapy2021

Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin.

Matthew Mannarino, Hosni Cherif, Li Li, Kai Sheng, Oded Rabau, Peter Jarzem, Michael H Weber, Jean A Ouellet, Lisbet Haglund

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Review
  3. Senolytic Therapy as a Preventive Strategy for Spine Degeneration and Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Technical insights and implications of thoracolumbar spine and neural tissue harvesting in recently deceased organ donors: a direct anterior approach integrated into multi-organ procurement protocols.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
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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

9 authors at 3 institutions in 1 country.

Matthew MannarinoDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Hosni CherifDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Li LiDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Kai ShengDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Oded RabauDepartment of Surgery, McGill Scoliosis and Spine Group, McGill University, Montreal, Canada.
Peter JarzemDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Michael H WeberDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Jean A OuelletDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada.
Lisbet HaglundDepartment of Surgery, Orthopaedic Research Lab, McGill University, Montreal, Canada. lisbet.haglund@mcgill.ca.ORCID 0000-0002-1288-2149
McGill University Health Centre · CAShriners Hospitals for Children - Canada · CAMontreal Children's Hospital · CA

Funding

Canadian Institutes of Health Research (CA) MOP-119564
6 · The paper itself

Abstract

backgroundThere is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence.

methodsCells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16

resultsAn increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16

conclusionsTaken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

Indexed as

Intervertebral DiscIntervertebral Disc DegenerationLow Back PainToll-Like Receptor 2BenzaldehydesCellular SenescenceHumans2-vanillinBenzaldehydesTLR2 protein, humanToll-Like Receptor 2Back painDegenerationInflammationIntervertebral disco-VanillinSenescenceSenolyticsToll-like receptor 2

Identifiers

PMID33863359
PMCPMC8051055
OpenAlexW3124057968

What OpenQuestion holds

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LicenceCC BY
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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.