Evidence map›Paper›PMID 42633138›Full record

ArticleJOR spine2026

Growth Plate Morphogens as Potential Modulators of Cellular Tissue Remodeling by Annulus Fibrosus Cells.

K Stradovnik-Poikilidis, M Teunissen, F M Riemers, M van Doeselaar, J Foolen, F Abinzano, M A Tryfonidou, S J P Callens, K Ito

Abstract read
In one paragraph

Article in JOR spine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

K Stradovnik-PoikilidisOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands.ORCID https://orcid.org/0009-0001-9819-6421
M TeunissenDepartment Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht the Netherlands.ORCID https://orcid.org/0000-0003-0119-3257
F M RiemersDepartment Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht the Netherlands.ORCID https://orcid.org/0000-0003-4732-9447
M van DoeselaarOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands.
J FoolenOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands.ORCID https://orcid.org/0000-0002-1065-7423
F AbinzanoOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands.ORCID https://orcid.org/0000-0003-1382-0107
M A TryfonidouDepartment Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht the Netherlands.ORCID https://orcid.org/0000-0002-2333-7162
S J P CallensOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands.ORCID https://orcid.org/0000-0002-0179-4098
K ItoOrthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands.ORCID https://orcid.org/0000-0002-7372-4072

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Adolescent Idiopathic Scoliosis (AIS) is a spinal deformity of unknown etiology that begins in the intervertebral disc and emerges during pubertal growth. In the vertebral growth plate, adjacent to the disc, powerful growth plate morphogens (GPMs) modulate this growth. We evaluated whether GPMs can also alter the capacity of annulus fibrosus (AF) disc cells to proliferate and/or remodel their extracellular matrix (ECM). Methods: AF cell responsiveness to seven GPMs was screened in monolayer culture by RT-qPCR for downstream signaling markers. GPMs and concentrations eliciting significant transcriptional responses were selected for deeper analysis. Bulk RNA sequencing (RNA-seq) was conducted on AF cells cultured in a 2.5D environment to preserve their native elongated phenotype. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology enrichment, focusing on ECM remodeling and cell-proliferation processes. Transcriptomic findings were corroborated by assessments of cell proliferation (DNA content), sulfated glycosaminoglycan (sGAG) levels, and matrix metalloproteinase (MMP) activity. Results: BMP-2, TGF-β1, and FGF-2 significantly altered AF cell expression of downstream target genes, whereas Ihh, PTHrP, Wnt-1, and FGF-18 did not. IGF-1 induced modest, dose-dependent gene expression changes that were not replicated by RNA-seq. BMP-2 and TGF-β1 upregulated genes associated with anabolic ECM remodeling. BMP-2 promoted a cartilage-like ECM with increased expression of type II-associated collagens, aggrecan, and hyaluronan synthesis. TGF-β1 promoted type I collagen-associated genes, collagen cross-linking, and myofibroblast activation. In contrast, FGF-2 activated transcriptional programs related to cell-cycle progression, collagen degradation, and increased GAG turnover. Functionally, we observed higher DNA content under BMP-2 and TGF-β1 stimulation and higher sGAG levels under BMP-2, TGF-β1, and FGF-2 treatment. Conclusion: BMP-2, TGF-β1, and FGF-2 can modulate AF cell behavior, influencing tissue remodeling and implicating their involvement in disc wedging during AIS onset.

Indexed as

adolescent idiopathic scoliosis (AIS)annulus fibrosusBMP‐2ECM remodelingFGF‐2intervertebral discTGF‐β

Identifiers

PMID42633138
PMCPMC13498972

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.