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Cited by 7Spine and Intervertebral Disc PathologyOsteoarthritis Treatment and MechanismsMicroRNA in disease regulation

ATF1 and miR-27b-3p drive intervertebral disc degeneration through the PPARG/NF-κB signaling axis

Open access
Guo, Wei, Mu, Kun, Geng, Jing-Chao, Xing, Hai-Yang, Dong, Yu, Liu, Wen-Dong, Wang, Shuan-Chi, Shi, Jia-Xiao +3 more·2025·Communications Biology
DOI 10.1038/s42003-025-08186-6PMC PMC12078598
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Abstract

Intervertebral disc degeneration (IDD) is a primary cause of degenerative disc disease; however, the mechanisms underlying it remain unknown. Although great efforts have been made to develop new regenerative therapies, their clinical success is limited. Recent research has indicated that microRNAs (miRNAs) are significantly involved in the progression of IDD. Investigating the role of miRNA intervention in IDD could facilitate the development of therapeutic strategies based on miRNAs. However, circulating miRNAs have not yet been recognized as standard biomarkers for IDD. In this study, we observed that the expression of miR-27b-3p was elevated in the blood and nucleus pulposus (NP) tissue of patients with IDD. Furthermore, reducing the expression of miR-27b-3p was shown to impede the progression of IDD. MiR-27b-3p could reduce the expression of collagen II and ACAN and promote the expression of MMP13 and ADAMT-5 in vitro and in vivo. miR-27b-3p aggravated IDD progression by directly targeting peroxisome proliferator-activated receptor gamma (PPARG), a negative regulator of the NF-κB signal pathway. This study also established that PPARG serves a protective role in IDD. The overexpression of PPARG was able to mitigate the detrimental effects caused by miR-27b-3p in NP cells and animal models of IDD, indicating that miR-27b-3p facilitates the progression of IDD through its interaction with PPARG. Additionally, the transcription factor ATF1 was found to enhance the expression of miR-27b-3p by targeting its promoter region, thereby promoting the degenerative impact of miR-27b-3p on NP cells. Given that miR-27b-3p can promote IDD both in vitro and in vivo, it holds potential as a biomarker, and the inhibition of miR-27b-3p expression may represent a novel therapeutic target for IDD.

AI snapshot

Written from the paper’s full text.

TL;DR

This study identifies miR-27b-3p as elevated in blood and nucleus pulposus of IDD patients and as a circulating miRNA associated with increased IDD risk, acting through PPARG repression and NF-κB activation. ATF1 transcriptionally activates miR-27b-3p, and inhibiting miR-27b-3p or overexpressing PPARG mitigates degenerative phenotypes in NP cells and rat IDD models.

Key findings

  • Mendelian randomization found four blood miRNAs significantly linked to increased IDD risk and three to reduced risk; the strongest was hsa-miR-27b-3p, where a 1-SD increase was associated with roughly an 8% rise in IDD likelihood. hsa-miR-339-5p was linked to a 3% reduction and hsa-miR-125b-5p to a 2% decrease.
  • miR-27b-3p was significantly increased in blood and NP tissue from 10 IDD patients versus 10 controls and positively correlated with Pfirrmann grade (r = 0.870, p < 0.001, n = 20). In NP cells, miR-27b-3p inhibition increased collagen II/ACAN and proliferation, while mimics increased MMP13/ADAMTS-5 and suppressed proliferation.
  • PPARG was identified as a direct miR-27b-3p target: PPARG was reduced in IDD blood and NP tissue, miR-27b-3p overexpression reduced PPARG mRNA, and luciferase activity of the wild-type PPARG 3′UTR was significantly decreased by miR-27b-3p. PPARG overexpression counteracted miR-27b-3p-induced degenerative changes in NP cells and rat discs, and reversed TNF-α-induced NF-κB p65 activation and catabolic marker increases.
  • ATF1 was identified as a transcription factor for miR-27b-3p: ATF1 overexpression promoted miR-27b-3p expression and degenerative NP cell phenotypes, while miR-27b-3p inhibition blocked ATF1 effects. Luciferase and ChIP–qPCR assays supported direct ATF1 binding to the miR-27b-3p promoter P1 region containing the motif TGAGTCA.

Methods

  • Two-sample Mendelian randomization used miRNA eQTL data from 5,329 participants and IDD GWAS summary statistics from FinnGen (37,636 cases and 270,964 controls); inverse variance-weighted was primary, with weighted median and MR-Egger sensitivity analyses and FDR < 0.05 for IDD.
  • Clinical samples included blood and NP tissue from 10 IDD patients and 10 age/sex-matched controls with traumatic vertebral fractures; analyses included qRT-PCR, immunofluorescence, FISH, CCK-8, Western blot, luciferase reporter assays, and ChIP–qPCR.
  • Rat injury-induced IDD was created by needle puncture at Co6/Co7; antagomir-27b-3p or controls were injected on days 1, 7, and 14, with disc samples collected at 6 and 12 weeks. PPARG adenovirus/siRNA experiments used 15 IDD model rats assigned to three groups (n = 5 each).

Limitations

  • The paper states that circulating miRNAs have not yet been recognized as standard biomarkers for IDD; that this study did not delve into the specific mechanisms through which PPARG influences NP cell degeneration; that further investigations are warranted in larger cohorts; and that other intersecting genes (NELFE, NFYC, RUNX2, TCF7L2) should be studied.
  • The paper also notes that miR-338-3p was associated with IDD in another study but was not identified here, and that other IDD-associated miRNAs had lower strength than miR-27b-3p and warrant additional investigation.
  • Evident from the text: human clinical samples were small (10 IDD patients and 10 controls), animal groups were small (n = 5 per group), and some in vitro experiments used n = 3; the statistics section states that multiple comparison corrections were not applied.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s42003-025-08186-6

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 10 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    PPARG is a negative regulator of the NF-kappaB signaling pathway.

    “Previous research indicated that PPARG was a negative regulator of NF-κB signal pathway26–28.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [26] Luo, X., Wu, J. & Wu, G. PPARgamma activation suppresses the expression of MMP9 by downregulating NF-kappaB post intracerebral hemorrhage. Neurosci. Lett. 752, 135770 (2021). source
    • cites [27] Lu, J. et al. Pseudolaric acid B ameliorates synovial inflammation and vessel formation by stabilizing PPARgamma to inhibit NF-kappaB signalling pathway. J. Cell. Mol. Med. 25, 6664–6678 (2021). source
    • cites [28] Solleti, S. K. et al. Airway epithelial cell PPARgamma modulates cigarette smoke-induced chemokine expression and emphysema susceptibility in mice. Am. J. Physiol. Lung Cell Mol. Physiol. 309, L293–L304 (2015). source
  • Premisecitation

    According to TransmiR, there is a single ATF1 binding site located in the promoter region of miR-27b-3p.

    “According to analysis by TransmiR32, there is a single ATF1 binding site located in the promoter region of miR-27b-3p.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [32] Tong, Z., Cui, Q., Wang, J. & Zhou, Y. TransmiR v2.0: an updated transcription factor-microRNA regulation database. Nucleic Acids Res. 47, D253–D258 (2019). source

      The Database Construction sections describe how TransmiR identifies putative transcription-factor binding in miRNA promoters, but do not report a result for ATF1 and miR-27b-3p. Searches for those terms found no passage establishing that there is exactly one binding site. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • Premisecitation

    ROS accumulation is an important stimulator for NF-κB signal activation.

    “ROS accumulation is an important stimulatory for NF-κB signal activation47–49”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [47] Feng, C. et al. ROS: crucial intermediators in the pathogenesis of intervertebral disc degeneration. Oxid. Med. Cell. Longev. 2017, 5601593 (2017). source
    • cites [48] Yao, M. et al. Marein protects human nucleus pulposus cells against high glucose-induced injury and extracellular matrix degradation at least partly by inhibition of ROS/NF-kappaB pathway. Int Immunopharmacol. 80, 106126 (2020). source
    • cites [49] Jiang, Y., Dong, G. & Song, Y. Nucleus pulposus cell senescence is alleviated by resveratrol through regulating the ROS/NF-kappaB pathway under high-magnitude compression. Biosci. Rep. 38, https://doi.org/10.1042/BSR20180670 (2018). source
  • Findingown data

    miR-27b-3p and PPARG mRNA co-localize in the same cytoplasmic region of NP cells.

    “both miR-27b-3p and PPARG mRNA were found to co-localize in the same cytoplasmic region of NP cells (Fig. 4F).”
    Quote in the paperNot a substantial claim
  • Findingown data

    hsa-miR-139-5p and hsa-miR-152 have comparable effects to hsa-miR-27b-3p on intervertebral disc degeneration risk.

    “Comparable effects were also found for hsa-miR-139-5p and hsa-miR-152.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 19
  • May combine two claims. 25

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ATF1 is known to influence the expression of matrix metalloproteinases across multiple diseases.

    “The transcription factor ATF1 is known to influence the expression of matrix metalloproteinases across multiple diseases30,31.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [30] Cui, J. et al. Activating transcription factor 1 promoted migration and invasion in lung cancer cells through regulating EGFR and MMP-2. Mol. Carcinog. 58, 1919–1924 (2019). source
    • cites [31] Li, T. et al. Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer. J. Transl. Med. 20, 169 (2022). source

      The Discussion reports that ATF1 increases MMP2 expression in lung cancer cells, and the Results show that phosphorylated ATF1 regulates MMP2 expression in gastric cancer cells. This supports an effect across more than one cancer, but the paper addresses only MMP2, not matrix metalloproteinases more broadly. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    ROS can lead to the loss of nucleus pulposus cells or diminish their functionality, resulting in an imbalance between anabolic and catabolic processes of the extracellular matrix characteristic of intervertebral disc degeneration.

    “Prior studies have shown that ROS can lead to the loss of NP cells or diminish their functionality, resulting in an imbalance between the anabolic and catabolic processes of the extracellular matrix (ECM), which is characteristic of IDD47.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [47] Feng, C. et al. ROS: crucial intermediators in the pathogenesis of intervertebral disc degeneration. Oxid. Med. Cell. Longev. 2017, 5601593 (2017). source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    TransmiR identified 142 predicted transcription factors that have the potential to regulate miRNA expression.

    “Using TransmiR (http://www.cuilab.cn/transmir), we identified a total of 142 predicted transcription factors that have the potential to regulate miRNA expression (Supplementary Data 2 in the Supplementary Data Excel file).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In rat intervertebral discs, overexpression of miR-27b-3p increases the mRNA and protein levels of MMP13 and ADAMT-5 while inhibiting the expression of collagen II and ACAN.

    “overexpression of miR-27b-3p increased the mRNA and protein levels of MMP13 and ADAMT-5 while inhibiting the expression of collagen II and ACAN (Fig. 6H–L).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Administering miR-27b-3p inhibitors downregulates MMP13 and ADAMT-5 and upregulates collagen II and ACAN in NP tissue of IDD rats.

    “Immunofluorescence analysis revealed that administering miR-27b-3p inhibitors down-regulated the expression levels of catabolic markers (MMP13 and ADAMT-5) and upregulated the expression levels of anabolic markers (collagen II and ACAN) in NP tissue (Fig. 3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ATF1 overexpression significantly promotes miR-27b-3p expression, and knockdown of ATF1 markedly inhibits miR-27b-3p expression.

    “ATF1 overexpression significantly promoted miR-27b-3p expression, and knockdown of ATF1 expression markedly inhibited the expression of miR-27b-3p.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The miR-27b-3p inhibitor significantly facilitates NP cell proliferation, while miR-27b-3p mimics notably suppress it.

    “the miR-27b-3p inhibitor significantly facilitated NP cell proliferation, while the miR-27b-3p mimics notably suppressed it (Fig. 2I).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    qRT-PCR confirms a significant reduction in MMP13 and ADAMT-5 mRNA levels and an increase in collagen II and ACAN mRNA levels in NP tissue of IDD rats treated with the miR-27b-3p inhibitor.

    “qRT-PCR analysis confirmed a significant reduction in the mRNA levels of MMP13 and ADAMT-5 in the NP tissue of IDD rats treated with the miR-27b-3p inhibitor, alongside an increase in collagen II and ACAN mRNA levels (Fig. 3C–F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Intradiscal application of miR-27b-3p leads to significant morphological degeneration of the intervertebral disc in rats, while overexpression of PPARG counters these effects.

    “The intradiscal application of miR-27b-3p led to significant morphological degeneration of the intervertebral disc, while the overexpression of PPARG countered these effects (Fig. 6G).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-27b-3p upregulates MMP13 and ADAMT-5 at both mRNA and protein levels while concurrently reducing the levels of collagen II and ACAN in NP cells.

    “miR-27b-3p resulted in an upregulation of MMP13 and ADAMT-5 at both mRNA and protein levels while concurrently reducing the levels of collagen II and ACAN.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overexpression of ATF1 decreases collagen II and ACAN mRNA expression while increasing the levels of MMP13 and ADAMT-5 mRNA in NP cells.

    “In NP cells, overexpression of ATF1 leads to a decrease in collagen II and ACAN mRNA expression while increasing the levels of MMP13 and ADAMT-5 mRNA. (Fig. 7E–H).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overexpression of miR-27b-3p results in a significant reduction in NP cell proliferation, which is notably reversed by overexpression of PPARG.

    “the overexpression of miR-27b-3p resulted in a significant reduction in proliferation, which was notably reversed by the overexpression of PPARG (Fig. 6F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overexpression of PPARG reverses the TNF-alpha-induced decrease in collagen II and ACAN levels, the increase in MMP13 and ADAMT-5 expression, and the activation of the NF-kappaB pathway in NP cells.

    “the overexpression of PPARG reversed the TNF-α induced decrease in collagen II and ACAN levels, as well as the increase in MMP13 and ADAMT-5 expression, along with the activation of the NF-κB pathway in NP cells (Fig. 5G).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overexpression of PPARG substantially promotes NP cell proliferation, while knockdown of PPARG leads to a marked decrease in proliferation.

    “it was observed that the overexpression of PPARG substantially promoted NP cell proliferation, while the knockdown of PPARG led to a marked decrease in proliferation (Fig. 5F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-27b-3p reduces collagen II and ACAN expression and promotes MMP13 and ADAMT-5 expression in vitro and in vivo.

    “MiR-27b-3p could reduce the expression of collagen II and ACAN and promote the expression of MMP13 and ADAMT-5 in vitro and in vivo.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    PPARG reduces the levels of catabolic markers MMP13 and ADAMT-5 and elevates the levels of anabolic markers collagen II and ACAN in NP cells at the protein level.

    “immunofluorescence analysis revealed that PPARG reduced the levels of catabolic markers (MMP13 and ADAMT-5) and elevated the levels of anabolic markers (collagen II and ACAN) in NP cells at the protein level (Fig. 5E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Four blood miRNAs are significantly linked to an increased risk of intervertebral disc degeneration, while three others are associated with a reduced risk.

    “Our analysis revealed that four blood miRNAs were significantly linked to an increased risk of IDD, while three others were associated with a reduced risk.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In degenerative NP cells, miR-27b-3p levels appear elevated while PPARG levels appear diminished.

    “levels of miR-27b-3p appeared elevated in degenerative NP cells, while those of PPARG appeared diminished (Fig. 4F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Knockdown of PPARG decreases collagen II and ACAN mRNA expression while increasing the levels of MMP13 and ADAMT-5 in NP cells.

    “Conversely, the knockdown of PPARG led to decreased expression of collagen II and ACAN mRNA while increasing the levels of MMP13 and ADAMT-5 (Fig. 5A–D).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    miR-338-3p was not identified as associated with intervertebral disc degeneration in the present study.

    “miR-338-3p was not identified as being associated with IDD in the present study”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The present study identified other miRNAs associated with intervertebral disc degeneration but with lower strength than miR-27b-3p.

    “the present study identified other miRNAs associated with IDD but with a lower strength than miR-27b-3p”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ATF1 reduces the levels of anabolic markers collagen II and ACAN and elevates the levels of catabolic markers MMP13 and ADAMT-5 in NP cells.

    “immunofluorescence analysis revealed that ATF1 reduced the levels of anabolic markers (collagen II and ACAN) and elevated the levels of catabolic markers (MMP13 and ADAMT-5) in NP cells (Fig. 7I).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Four other intersecting genes (NELFE, NFYC, RUNX2, and TCF7L2) were identified alongside ATF1.

    “Four other intersecting genes were identified alongside ATF1 (NELFE, NFYC, RUNX2, and TCF7L2)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Knockdown of ATF1 results in elevated expression of collagen II and ACAN mRNA while reducing the levels of MMP13 and ADAMT-5 in NP cells.

    “the knockdown of ATF1 resulted in elevated expression of collagen II and ACAN mRNA while reducing the levels of MMP13 and ADAMT-5 (Fig. 7E–H).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    PPARG is crucial for preventing the degeneration of NP cells, likely through inhibiting the activation of the NF-kappaB pathway.

    “In conclusion, PPARG is crucial for preventing the degeneration of NP cells, likely through inhibiting the activation of the NF-κB pathway.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Increased levels of miR-27b-3p inhibit matrix synthesis and reduce the proliferation of NP cells.

    “Therefore, our findings suggest that increased level of miR-27b-3p inhibits matrix synthesis and reduces the proliferation of NP cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    ATF1 promotes the expression of miR-27b-3p, which subsequently affects functions related to the development of intervertebral disc degeneration.

    “In summary, the transcription factor ATF1 promotes the expression of miR-27b-3p, which subsequently affects the functions of miR-27b-3p related to the development of IDD (Fig. 8G).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    All comparisons were predefined and hypothesis-driven.

    “All comparisons were predefined and hypothesis-driven.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Stringent quality control measures were implemented for SNPs.

    “stringent quality control measures were implemented for SNPs”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Supplementary analyses were performed using multiple MR methods to ensure the reliability of the findings.

    “Supplementary analyses were also performed using multiple MR methods to ensure the reliability of our findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A total of 15 IDD model rats were randomly assigned to three groups (n = 5 each).

    “A total of 15 IDD model rats were included in this research and assigned to three groups randomly (n = 5 each).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    All experiments were independently repeated at least three times using cells from a single isolation per experiment.

    “All experiments were independently repeated at least three times using cells from a single isolation per experiment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Rats were randomly divided into groups.

    “Twenty male rats that had previously undergone the injury-induced IDD procedure were randomly divided into three groups (n = 5 each)”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    A Benjamini-Hochberg adjusted false discovery rate threshold of 0.1 was implemented to reduce false-positive findings.

    “To reduce the likelihood of false-positive findings, a Benjamini–Hochberg adjusted false discovery rate (FDR) threshold of 0.1 was implemented”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    ATF1 transcriptionally activates miR-27b-3p, leading to inhibition of PPARG and NF-kappaB signal pathway activation, which decreases collagen II and ACAN in NP and accelerates the progression of intervertebral disc degeneration.

    “This study illustrated that ATF1 transcriptionally activates miR-27b-3p, leading to the inhibition of the downstream target PPARG and NF-κB signal pathway activation, which ultimately contributes to the decrease of collagen II and ACAN in NP and accelerates the progression of IDD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    FDR was utilized to mitigate potential type I errors with a value less than 0.05 for IDD.

    “FDR was utilized to mitigate potential type I errors with a value less than 0.05 for IDD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Low PPARG expression leads to ROS accumulation in nucleus pulposus cells, which activates the NF-κB signaling pathway and promotes the development of intervertebral disc degeneration.

    “We suggest that low PPARG expression leads to ROS accumulation in NP cells, which activates the NF-κB signal pathway and promotes the development of IDD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Targeted interventions aimed at the ATF1/miR-27b-3p/PPARG pathways may present novel therapeutic avenues for patients with intervertebral disc degeneration.

    “targeted interventions aimed at the ATF1/miR-27b-3p/PPARG pathways may present novel therapeutic avenues for patients suffering from IDD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Multiple comparison corrections were not applied to avoid overcorrection and loss of statistical power.

    “Given the limited number of independent tests per experiment, multiple comparison corrections were not applied to avoid overcorrection and loss of statistical power.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    IDD cases were clinically diagnosed by two experienced spine surgeons through physical examinations and MRI assessments.

    “All IDD cases were clinically diagnosed by two experienced spine surgeons through physical examinations and MRI assessments.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    MR-Egger regression was used to identify and adjust for pleiotropic effects.

    “We utilized the MR-Egger regression method to identify and adjust for pleiotropic effects”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    The weighted median method was used to address potential violations of the IVW assumption, allowing for up to half of the instrumental variables to be invalid.

    “The study utilized the weighted median method to address potential violations of the assumption of IVW analysis, allowing for the presence of up to half of the instrumental variables being invalid.”
    Quote in the paperSubstantial claim
42 of 42

  • The paper relies on this without support.

    Circulating miRNAs have not yet been developed or recognized as standard clinical biomarkers for intervertebral disc degeneration.

    “However, circulating miRNAs have not yet been recognized as standard biomarkers for IDD.”
    “Despite their potential, circulating miRNAs have not yet been developed as standard clinical biomarkers for IDD.”

  • The paper relies on this without support.

    The transcription factors that modulate miRNA expression in the context of intervertebral disc degeneration have yet to be investigated.

    “While numerous transcription factors involved in miRNA expression have been recognized21–24, the transcription factors that modulate miRNA expression in the context of IDD have yet to be investigated.”

  • The paper relies on this without support.

    The interplay between various transcription factors and their downstream targets is not fully understood.

    “However, the interplay between various transcription factors and their downstream targets is not fully understood.”

  • The paper relies on this without support.

    The mechanisms underlying intervertebral disc degeneration remain unknown.

    “Intervertebral disc degeneration (IDD) is a primary cause of degenerative disc disease; however, the mechanisms underlying it remain unknown.”

  • The authors state this as an assumption.

    There is no horizontal pleiotropy among the single nucleotide polymorphisms used in the inverse variance-weighted Mendelian randomization analysis.

    “based on the premise that there is no horizontal pleiotropy among the single nucleotide polymorphisms (SNPs)”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Figure 2 title names a different miRNA strand

    Minor

    The figure title identifies miR-27b-5p, whereas its caption identifies the measured miRNA as miR-27b-3p.

  • Rat group count does not match the stated total

    Minor

    Three groups of five rats would contain 15 rats, not 20. The subsequent list names four groups, which would account for all 20 rats.

    Reported 20 · recomputed 15

  • Opposite miR-27b-3p interventions are said to counteract ATF1

    Minor

    The results say miR-27b-3p counteracted ATF1-induced degeneration, then say inhibition of miR-27b-3p reduced the detrimental effects of ATF1 overexpression.

  • Healthy rat group is also described as having undergone injury

    Minor

    The methods say all 20 rats had undergone the injury-induced IDD procedure, but designate Group 1 as healthy rats with no interventions.

4 of 4

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1042/bsr20180670

    Major

    The cited work was retracted on 2024-08-22 (notice 10.1042/bsr-2018-0670_ret), before this paper was published (2025-05-14). Its authors could have known.

    Cited work 10.1042/bsr20180670 · retracted 2024-08-22 · notice 10.1042/bsr-2018-0670_ret · this paper published 2025-05-14

1 of 1

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Authors
Guo, W., Mu, K., Geng, J.-C., Xing, H.-Y., Dong, Y., Liu, W.-D., Wang, S.-C., Shi, J.-X., Xing, B.-R., Zhao, J.-Y., & Li, X.-M.
Affiliations
Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province (CN)
Corresponding author
  • Guo, Wei
  • Li, Xiao-Ming
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2025-05-14
Volume
8
Issue
1
Pages
751-751
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-025-08186-6
PMC
PMC12078598
OpenAlex
W4410360512
Cited by
7
References
53
Citations by year
2026: 5 · 2025: 2
FWCI
4.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spine and Intervertebral Disc Pathology
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
intervertebral disc degeneration, miR-27b-3p, ATF1, PPARγ, NF-κB signaling, nucleus pulposus cells, microRNA biomarkers, type II collagen, aggrecan, MMP-13, therapeutic target
MeSH terms
Nucleus Pulposus, Adult, Animals, Female, Humans, Male, Middle Aged, Signal Transduction, NF-kappa B, MicroRNAs, PPAR gamma, Mice, Rats, Intervertebral Disc Degeneration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-20.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-20.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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