ArticleJournal of orthopaedic surgery and research2025
Epigenetic silencing of SPHK1-IRF7 axis drives inflammaging in age-related meniscus degeneration via sphingolipid-immune dysregulation.
Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
backgroundAge-related meniscus injury (MI) involves inflammaging, but biomarkers and mechanisms remain unclear.
methodsRibonucleic acid (RNA) sequencing of meniscal tissues from 15 young (< 45 years) and 15 aging (≥ 45 years) MI patients (training dataset) identified differentially expressed inflammation-related genes (DE-IRGs). Biomarkers were screened via least absolute shrinkage and selection operator (LASSO) and support vector machines-recursive feature elimination (SVM-RFE) in the training dataset and validated through GSE191157 (testing dataset) and immunohistochemistry (IHC) staining in additional clinical specimens. Support vector machines (SVM) model and artificial neural network (ANN) model were constructed to predict the diagnostic performance of biomarkers for aging MI. Moreover, biomarkers enrichment analysis, and correlation among biomarkers, function-related genes, immune factors and immune cells were completed. Finally, transcription factor (TF)-biomarker-microRNAs (miRNAs) and competing endogenous RNA (ceRNA) regulatory networks analysis, and drug prediction were performed.
resultsIRF7 and SPHK1 were significantly downregulated in aging MI and predicted aging MI with high accuracy (area under the curve (AUC) > 0.7). Both biomarkers correlated with chemokine/cytokine pathways, immune senescence (positively with γδT cells/Th17/monocytes; negatively with LAG3/IL6R/TNFSF13), and sphingolipid metabolism (PLPP2 synergy) (|r| = 0.49 ~ 0.86, p < 0.05). Regulatory networks implicated NORAD lncRNA (upregulated) negatively regulated the expression of SPHK1 and IRF7 (r<-0.90, p < 0.05), while transcription factors E2F4 and KLF5 (downregulated) positively regulated their expression (r > 0.95, p < 0.05). Clinically, SPHK1 and IRF7 positively correlated with preoperative Lysholm score (SPHK1: r = 0.66; IRF7: r = 0.61; p < 0.05) and negatively with preoperative VAS (SPHK1: r=-0.58; IRF7: r=-0.58; p < 0.05) in aging MI. Two drugs (decitabine, acetaminophen) targeting these biomarkers were predicted.
conclusionSPHK1 and IRF7 drive inflammaging via sphingolipid-immune crosstalk and epigenetic silencing, offering diagnostic and therapeutic potential.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.