Evidence map›Paper›PMID 40165259›Full record

ArticleArthritis research & therapy2025

The TLR-M-CSF axis is implicated in increased bone turnover and curve progression in adolescent idiopathic scoliosis.

Kai Sheng, Daniel G Bisson, Neil Saran, Jake Bourdages, Christopher Coluni, Kirby Upshaw, Kerstin Tiedemann, Svetlana V Komarova, Jean A Ouellet, Lisbet Haglund

Abstract read
In one paragraph

Article in Arthritis research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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
    Article
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  4. 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

10 authors.

Kai ShengShriners Hospital for Children, Montreal, QC, Canada.
Daniel G BissonShriners Hospital for Children, Montreal, QC, Canada.
Neil SaranShriners Hospital for Children, Montreal, QC, Canada.
Jake BourdagesShriners Hospital for Children, Montreal, QC, Canada.
Christopher ColuniShriners Hospital for Children, Montreal, QC, Canada.
Kirby UpshawShriners Hospital for Children, Montreal, QC, Canada.
Kerstin TiedemannShriners Hospital for Children, Montreal, QC, Canada.
Svetlana V KomarovaUniversity of Alberta, Edmonton, AB, Canada.
Jean A OuelletShriners Hospital for Children, Montreal, QC, Canada.
Lisbet HaglundShriners Hospital for Children, Montreal, QC, Canada. lisbet.haglund@mcgill.ca.

Funding

CIHR PJT-183867Shriner's Hospital for Children 72002-CAN-23
6 · The paper itself

Abstract

backgroundFacet joint osteoarthritis (OA) is prevalent in patients with adolescent idiopathic scoliosis (AIS). The most pronounced OA presents above and below the curve's apex where the intervertebral rotation is the greatest. This indicates that facet joint OA is implicated and potentially contributes to AIS progression. OA impacts both cartilage and bone and we have previously demonstrated an association between lower bone quality and more severe OA in AIS facet joints. This study aimed to further investigate the molecular mechanisms underlying cartilage-bone crosstalk in the facet joints of patients with AIS.

methodsUnbiased deep RNA sequencing was performed to compare gene expression in facet joint chondrocytes of age-matched AIS patients and non-scoliotic individuals. Differentially expressed genes of interest were validated through qPCR and ELISA in a larger sample cohort. Key regulatory pathways involved in cartilage-bone crosstalk were identified through bioinformatic analysis. Functional studies were conducted by treating chondrocytes with TLR2 and TLR4 agonists, collecting conditioned media, and administering it to an in vitro osteoclastogenesis model. The expression of M-CSF, a key regulatory factor influencing osteoclast proliferation, was measured in individual facet joint cartilage samples at different spinal levels and correlated with cartilage morphological grade and 3D structural parameters extracted from spine reconstruction.

resultsOne thousand four hundred twenty six upregulated genes were detected, and gene ontology analysis revealed a significant enrichment of the TLR pathway, and bone-regulating biological processes in AIS chondrocytes. TLR activation of AIS chondrocytes induced expression of bone-regulating factors, including M-CSF, a key regulator of osteoclast proliferation. Furthermore, secreted factors from AIS chondrocytes enhanced osteoclast proliferation and maturation, with a stronger effect observed following TLR pre-activation. Clinically, M-CSF expression was found to correlate strongly with increased OA severity and a greater degree of intervertebral axial rotation.

conclusionsTogether, our findings suggest that the TLR-M-CSF axis is implicated in osteoclastogenesis, resulting in increased bone turnover and may contribute to curve progression in AIS patients.

Indexed as

Bone RemodelingScoliosisToll-Like ReceptorsAdolescentChildChondrocytesDisease ProgressionFemaleHumansMaleToll-Like ReceptorsCrosstalkFacet jointsOsteoarthritisOsteoclastScoliosisSubchondral bone

Identifiers

PMID40165259
PMCPMC11956469

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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.