ArticleOsteoarthritis and cartilage2025
TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair potential in degenerative conditions.
Article in Osteoarthritis and cartilage, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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.
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Who cites it
2 citing papers in PubMed.
- Mechanism-centered target discovery across glomerulonephritis phenotypes: an integrative multi-omics study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- TNFα Receptor 1 and Not Receptor 2 Affect Annulus Fibrosus and Nucleus Pulposus Response to Cytokine Challenge in a Rat Model.JOR spine · 2025Article
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11 authors.
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Abstract
objectiveTo identify mechanisms and treatment targets in painful intervertebral disc (IVD) degeneration (IVDD) progression with a focus on pro-inflammatory tumor necrosis factor-alpha (TNFα)-receptor-1 (TNFR1) and pro-reparative TNFα receptor-2 (TNFR2) signaling.
designIVDD tissues and cells from IVDD and autopsy subjects were analyzed with single-cell RNA-sequencing to identify cell populations expressing TNFR1 and TNFR2, and multiplexed array to identify inflammatory proteins in IVDD conditioned media (CM). Bulk RNA-seq evaluated inflammatory and cell cycle states of human annulus fibrosus (hAF) cells challenged with CM. hAF cell responses to TNFR1 and TNFR2 modulation were evaluated by treatment with TNFR1- and TNFR2-blocking antibodies and TNFR2-activator Atsttrin.
resultsIVDD CM chemokines and cytokines were expressed primarily by a small macrophage population and at low levels by native IVD cells. CM-treated hAF cells exhibited TNFα-signaling responses with reduced metabolic rates (MTT: 0.75 [95%CI:0.67 to 0.82]), limited inflammatory responses (inferred from heatmap of 50 differentially expressed genes), and senescence (10.4% SA-β-Gal+ cells [95%CI:6.99 to 13.8]). TNFR1-inhibition sufficiently restored hAF cell metabolism to enable robust pro-inflammatory responses to the complex IVDD CM cytokine mixture (multiple assays,). TNFR2-staining was limited on human IVD cell membranes and TNFR2 modulation had no effect on hAF cells, together suggesting a lack of TNFR2-signaling in native IVD cells.
conclusionsSecreted proteins from IVDD CM caused hAF cells to have reduced metabolic rates, attenuated inflammatory responses, and senescence indicating a TNFR1-dominated response with metabolic impairment. Meanwhile, human IVD cells lacked reparative TNFR2-signaling since its modulation caused no effects, to suggest enhanced TNFR2-signaling in IVD repair may need recruitment or delivery of macrophages or other TNFR2-expressing cells.
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