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Review Open Access

Epigenetic research methods and animal models for intervertebral disc degeneration (Review)

  • Authors:
    • Xinliang Cui
    • Li Zeng
    • Wei Zhang
    • Leimin Xi
    • Rui Wang
    • Diff Jia
    • Safa
    • Haoyu Feng
    • Huidong Jia
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi 030032, P.R. China, Center for Biomedical Clinical Research, The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi 030032, P.R. China, Medical Science Division, University of Oxford, Oxford OX1 4AR, UK
    Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 203
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    Published online on: May 21, 2026
       https://doi.org/10.3892/mmr.2026.13913
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Abstract

Intervertebral disc degeneration (IVDD) is increasingly recognized as a systemic collapse of the epigenetic regulatory network, driven by cellular senescence and environmental stressors. The present review provides an overview of the epigenetic regulatory mechanisms governing IVDD, focusing on the dynamic interplay between DNA methylation, histone modifications, N6‑methyladenosine RNA methylation and the non‑coding RNA regulatory triad (microRNAs, long non‑coding RNAs and circular RNAs). The present study evaluates advanced research methodologies (ranging from site‑specific methylation typing and transposase accessible chromatin sequencing to single‑cell multi‑omics and artificial intelligence‑driven predictive modeling) that resolve the spatial and cellular heterogeneities of the degenerating disc niche. Furthermore, the translational constraints of current animal models were critically assessed, advocating for a strategic shift from acute needle‑puncture insults to physiologically relevant aging and genetically engineered progeroid models to better recapitulate human ‘epigenetic drift’. Finally, the therapeutic potential of targeted epigenetic editing via CRISPR/dCas9 systems and the development of stimuli‑responsive nanocarriers for precision delivery are highlighted. By bridging methodological innovation with robust model selection, the present review offers a roadmap for transitioning molecular insights into clinical regenerative therapies for spinal health.
View Figures

Figure 1

Epigenetic toolkit in IVDD:
Mechanisms, techniques, models and translational applications. (A)
Core epigenetic mechanisms in IVDD. (B) Core epigenetic study
techniques (C) Animal models in IVDD epigenetics. (D) Therapeutic
epigenetic reprogramming and interventions. 5-mc, 5-methylcytosine;
5-hmc, 5-hydroxymethylcytosine; DNMTs, DNA methyltransferases;
TETs, Ten-eleven translocation enzymes; HATs, histone
acetyltransferases; MSP, methylation-specific PCR; BSP, bisulfite
sequencing PCR; WGBS, whole-genome bisulfite sequencing; MeDIP-seq,
methylated DNA immunoprecipitation sequencing; CHIP-Seq, chromatin
immunoprecipitation sequencing; CUT&Tag, Cleavage Under Targets
and Tagmentation; CUT&RUN, Cleavage Under Targets and Release
Using Nuclease; ATAC-seq, assay for transposase-accessible
chromatin using sequencing; MeRIP-seq, methylated RNA
immunoprecipitation sequencing; m6A-seq,
N6-methyladenosine sequencing; AAV, adeno-associated virus; LV,
lentivirus; LNPs, lipid nanoparticles; PNP, polymeric
nanoparticles; eExos, engineered exosomes; miRNA, microRNA, HDAC,
histone deacetylase.
View References

1 

Maher C, Underwood M and Buchbinder R: Non-specific low back pain. Lancet. 389:736–747. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Samanta A, Lufkin T and Kraus P: Intervertebral disc degeneration-current therapeutic options and challenges. Front Public Health. 11:11567492023. View Article : Google Scholar : PubMed/NCBI

3 

Taylor W and Erwin WM: Intervertebral disc degeneration and regeneration: New molecular mechanisms and therapeutics: Obstacles and potential breakthrough technologies. Cells. 13:21032024. View Article : Google Scholar : PubMed/NCBI

4 

Mohd Isa IL, Teoh SL, Mohd Nor NH and Mokhtar SA: Discogenic low back pain: Anatomy, pathophysiology and treatments of intervertebral disc degeneration. Int J Mol Sci. 24:2082022. View Article : Google Scholar : PubMed/NCBI

5 

Kirnaz S, Capadona C, Wong T, Goldberg JL, Medary B, Sommer F, McGrath LB Jr and Härtl R: Fundamentals of intervertebral disc degeneration. World Neurosurg. 157:264–273. 2022. View Article : Google Scholar : PubMed/NCBI

6 

Du J: Global, regional, and national burden of low back pain: Findings from the global burden of disease study 2021 and projections to 2050. Spine (Phila Pa 1976). 50:E3892025. View Article : Google Scholar : PubMed/NCBI

7 

Oichi T, Taniguchi Y, Oshima Y, Tanaka S and Saito T: Pathomechanism of intervertebral disc degeneration. JOR spine. 3:e10762020. View Article : Google Scholar : PubMed/NCBI

8 

Ferreira JR, Moura ML, Pilão S, Castro AL, Fiordalisi M, Leite Pereira C, Caldeira J and Gonçalves RM: Decoding intervertebral disc cell populations: Challenges in isolation and phenotype definition. Tissue Eng Part B Rev. tenteb20240350. 2025.(Epub ahead of print). PubMed/NCBI

9 

Urban JPG and Fairbank JCT: Current perspectives on the role of biomechanical loading and genetics in development of disc degeneration and low back pain; a narrative review. J Biomech. 102:1095732020. View Article : Google Scholar : PubMed/NCBI

10 

Guo W, Li BL, Zhao JY, Li XM and Wang LF: Causal associations between modifiable risk factors and intervertebral disc degeneration. Spine J. 24:195–209. 2024. View Article : Google Scholar : PubMed/NCBI

11 

Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA and Kang JD: Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J. 13:331–341. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Tseranidou S, Segarra-Queralt M, Chemorion FK, Le Maitre CL, Piñero J and Noailly J: Nucleus pulposus cell network modelling in the intervertebral disc. NPJ Syst Biol Appl. 11:132025. View Article : Google Scholar : PubMed/NCBI

13 

Kaneda G, Zila L, Wechsler JT, Shafi K, Cheema K, Bae H, Kim SD, Tuchman A, Li D and Sheyn D: What a pain in the back: Etiology, diagnosis and future treatment directions for discogenic low back pain. Bone Res. 13:892025. View Article : Google Scholar : PubMed/NCBI

14 

Kang L, Zhang H, Jia C, Zhang R and Shen C: Epigenetic modifications of inflammation in intervertebral disc degeneration. Ageing Res Rev. 87:1019022023. View Article : Google Scholar : PubMed/NCBI

15 

Ząbek Z, Wyczałkowska-Tomasik A, Poboży K, Adamus JP, Turek G, Ząbek M and Pączek L: Understanding the microenvironment of intervertebral disc degeneration: A comprehensive review of pathophysiological insights and therapeutic implications. Int J Mol Sci. 26:99382025. View Article : Google Scholar : PubMed/NCBI

16 

Xu J, Shao T, Lou J, Zhang J and Xia C: Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration. Front Pharmacol. 14:11729202023. View Article : Google Scholar : PubMed/NCBI

17 

Hickman TT, Rathan-Kumar S and Peck SH: Development, pathogenesis, and regeneration of the intervertebral disc: Current and future insights spanning traditional to omics methods. Front Cell Dev Biol. 10:8418312022. View Article : Google Scholar : PubMed/NCBI

18 

Li G, Zhang W, Liang H and Yang C: Epigenetic regulation in intervertebral disc degeneration. Trends Mol Med. 28:803–805. 2022. View Article : Google Scholar : PubMed/NCBI

19 

Zhang Y, Wang J, Hua D, Fan C, He W, Deng Y, Tang M, Geng D, Wu X and Mao H: Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases. J Orthop Translat. 55:245–266. 2025. View Article : Google Scholar : PubMed/NCBI

20 

Jiang C, Chen Z, Wang X, Zhang Y, Guo X, Xu Z, Yang H and Hao D: The potential mechanisms and application prospects of non-coding RNAs in intervertebral disc degeneration. Front Endocrinol (Lausanne). 13:10811852022. View Article : Google Scholar : PubMed/NCBI

21 

Tao Y, Yu X, Li X, Xu Y, Wang H, Zhang L, Lin R, Wang Y and Fan P: M6A methylation-regulated autophagy may be a new therapeutic target for intervertebral disc degeneration. Cell Biol Int. 48:389–403. 2024. View Article : Google Scholar : PubMed/NCBI

22 

Bertucci-Richter EM and Parrott BB: The rate of epigenetic drift scales with maximum lifespan across mammals. Nat Commun. 14:77312023. View Article : Google Scholar : PubMed/NCBI

23 

Moqri M, Poganik JR, Horvath S and Gladyshev VN: What makes biological age epigenetic clocks tick. Nat Aging. 5:335–336. 2025. View Article : Google Scholar : PubMed/NCBI

24 

Bertucci-Richter EM, Shealy EP and Parrott BB: Epigenetic drift underlies epigenetic clock signals, but displays distinct responses to lifespan interventions, development, and cellular dedifferentiation. Aging (Albany NY). 16:1002–1020. 2024. View Article : Google Scholar : PubMed/NCBI

25 

Diwan AD and Melrose J: Intervertebral disc degeneration and how it leads to low back pain. JOR Spine. 6:e12312022. View Article : Google Scholar : PubMed/NCBI

26 

Younesian S, Mohammadi MH, Younesian O, Momeny M, Ghaffari SH and Bashash D: DNA methylation in human diseases. Heliyon. 10:e323662024. View Article : Google Scholar : PubMed/NCBI

27 

Wu X and Zhang Y: TET-mediated active DNA demethylation: Mechanism, function and beyond. Nat Rev Genet. 18:517–534. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Li G, Luo R, Zhang W, He S, Wang B, Liang H, Song Y, Ke W, Shi Y, Feng X, et al: m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency. Clin Transl Med. 12:e7652022. View Article : Google Scholar : PubMed/NCBI

29 

Chen J, Yang X, Li Q, Ma J, Li H, Wang L, Chen Z and Quan Z: Inhibiting DNA methyltransferase DNMT3B confers protection against ferroptosis in nucleus pulposus and ameliorates intervertebral disc degeneration via upregulating SLC40A1. Free Radic Biol Med. 220:139–153. 2024. View Article : Google Scholar : PubMed/NCBI

30 

Cheng P, Li H, Chen HW, Wang ZQ, Li PW and Zhang HH: 5-Azacytidine inhibits endoplasmic reticulum stress and apoptosis of nucleus pulposus cells by preserving PPARγ via promoter demethylation. In Vitro Cell Dev Biol Anim. 61:288–297. 2025. View Article : Google Scholar : PubMed/NCBI

31 

Cheng P, Wei HZ, Chen HW, Wang ZQ, Mao P and Zhang HH: DNMT3a-mediated methylation of PPARγ promote intervertebral disc degeneration by regulating the NF-κB pathway. J Cell Mol Med. 28:e180482024. View Article : Google Scholar : PubMed/NCBI

32 

Yeater TD, Kawarai Y, Lee S, Belani KG, Beebe DS, Sheyn D, Pinto MR and Stone LS: Investigating the epigenetic landscape of symptomatic disk degeneration: A case study. Pain Rep. 10:e12372025. View Article : Google Scholar : PubMed/NCBI

33 

Hong JY, Kim H, Jeon WJ, Lee J, Yeo C, Lee YJ and Ha IH: Epigenetic changes within the annulus fibrosus by DNA methylation in rat intervertebral disc degeneration model. Cells. 11:35472022. View Article : Google Scholar : PubMed/NCBI

34 

Karchevskaya AE, Poluektov YM and Korolishin VA: Understanding intervertebral disc degeneration: Background factors and the role of initial injury. Biomedicines. 11:27142023. View Article : Google Scholar : PubMed/NCBI

35 

Tajerian M, Alvarado S, Millecamps M, Dashwood T, Anderson KM, Haglund L, Ouellet J, Szyf M and Stone LS: DNA methylation of SPARC and chronic low back pain. Mol Pain. 7:652011. View Article : Google Scholar : PubMed/NCBI

36 

Li S and Tollefsbol TO: DNA methylation methods: Global DNA methylation and methylomic analyses. Methods. 187:28–43. 2021. View Article : Google Scholar : PubMed/NCBI

37 

Ikuno A, Akeda K, Takebayashi SI, Shimaoka M, Okumura K and Sudo A: Genome-wide analysis of DNA methylation profile identifies differentially methylated loci associated with human intervertebral disc degeneration. PLoS One. 14:e02221882019. View Article : Google Scholar : PubMed/NCBI

38 

Sun P, Huang T, Huang C, Wang Y and Tang D: Role of histone modification in the occurrence and development of osteoporosis. Front Endocrinol (Lausanne). 13:9641032022. View Article : Google Scholar : PubMed/NCBI

39 

Dueva R, Akopyan K, Pederiva C, Trevisan D, Dhanjal S, Lindqvist A and Farnebo M: Neutralization of the positive charges on histone tails by RNA promotes an open chromatin structure. Cell Chem Biol. 26:1436–1449.e5. 2019. View Article : Google Scholar : PubMed/NCBI

40 

Higashiyama R, Miyaki S, Yamashita S, Yoshitaka T, Lindman G, Ito Y, Sasho T, Takahashi K, Lotz M and Asahara H: Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis. Mod Rheumatol. 20:11–17. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Zheng Q, Li XX, Xiao L, Shao S, Jiang H, Zhang XL, Sun LY and Xu HG: MicroRNA-365 functions as a mechanosensitive microRNA to inhibit end plate chondrocyte degeneration by targeting histone deacetylase 4. Bone. 128:1150522019. View Article : Google Scholar : PubMed/NCBI

42 

Xiao L, Gong D, Liang L, Liang A, Liang H, Xu X and Teng H: Inhibition of HDAC4 by GSK3β leads to downregulation of KLF5 and ASK1 and prevents the progression of intravertebral disc degeneration. Clin Epigenetics. 13:532021. View Article : Google Scholar : PubMed/NCBI

43 

Makki MS and Haqqi TM: Histone deacetylase inhibitor vorinostat (SAHA) suppresses IL-1β-induced matrix metallopeptidase-13 expression by inhibiting IL-6 in osteoarthritis chondrocyte. Am J Pathol. 186:2701–2708. 2016. View Article : Google Scholar : PubMed/NCBI

44 

Lei M, Lin H, Shi D, Hong P, Song H, Herman B, Liao Z and Yang C: Molecular mechanism and therapeutic potential of HDAC9 in intervertebral disc degeneration. Cell Mol Biol Lett. 28:1042023. View Article : Google Scholar : PubMed/NCBI

45 

Ramteke P, Watson B, Toci M, Tran VA, Johnston S, Tsingas M, Barve RA, Mitra R, Loeser RF, Collins JA and Risbud MV: SIRT6 loss causes intervertebral disc degeneration in mice by promoting senescence and SASP status. bioRxiv [Preprint]. 2024.09.09.612072. 2024.PubMed/NCBI

46 

Ma W, Wang W, Zhao L, Fan J, Liu L, Huang L, Peng B, Wang J, Xu B, Liu H, et al: Reprogramming to restore youthful epigenetics of senescent nucleus pulposus cells for mitigating intervertebral disc degeneration and alleviating low back pain. Bone Res. 13:352025. View Article : Google Scholar : PubMed/NCBI

47 

Yao Q, Lei Y, Zhang Y, Chen H, Dong X, Ye Z and Liang H: EZH2-H3K27me3-mediated epigenetic silencing of DKK1 induces nucleus pulposus cell pyroptosis in intervertebral disc degeneration by activating NLRP3 and NAIP/NLRC4. Inflammation. 48:902–918. 2025. View Article : Google Scholar : PubMed/NCBI

48 

Zhou M, He SJ, Liu W, Yang MJ, Hou ZY, Meng Q and Qian ZL: EZH2 upregulates the expression of MAPK1 to promote intervertebral disc degeneration via suppression of miR-129-5p. J Gene Med. 24:e33952022. View Article : Google Scholar : PubMed/NCBI

49 

Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al: Metabolic regulation of gene expression by histone lactylation. Nature. 574:575–580. 2019. View Article : Google Scholar : PubMed/NCBI

50 

Sun K, Shi Y, Yan C, Wang S, Han L, Li F, Xu X, Wang Y, Sun J, Kang Z and Shi J: Glycolysis-derived lactate induces ACSL4 expression and lactylation to activate ferroptosis during intervertebral disc degeneration. Adv Sci (Weinh). 12:e24161492025. View Article : Google Scholar : PubMed/NCBI

51 

Shi Y, Li F, Lin W, Han L, Wang J, Yan C, Sun J, Ji C, Shi J and Sun K: Integrating bulk RNA and single-cell RNA sequencing identifies and validates lactylation-related signatures for intervertebral disc degeneration. J Cell Mol Med. 28:e702622024. View Article : Google Scholar : PubMed/NCBI

52 

Zheng SK, Zhao XK, Wu H, He DW, Xiong L and Cheng XG: Oxidative stress-induced EGR1 upregulation promotes NR4A3-mediated nucleus pulposus cells apoptosis in intervertebral disc degeneration. Aging (Albany NY). 16:10216–10238. 2024. View Article : Google Scholar : PubMed/NCBI

53 

Saotome M, Goodman J and Takaku M: Capturing chromatin organization by MNase-seq and ATAC-seq. Methods Mol Biol. 2889:167–180. 2025. View Article : Google Scholar : PubMed/NCBI

54 

Shu S, Zhang X, Feng Z, Liu Z, Wang K, Li F, Wu Y, Shi B, Qiu Y, Zhu Z and Bao H: Upregulated CEMIP promotes intervertebral disc degeneration via AP-1-mediated change in chromatin accessibility. Clin Transl Med. 15:e703222025. View Article : Google Scholar : PubMed/NCBI

55 

Zhu D, Liang H, Tong B, Du Z, Li G, Zhang W, Wu D, Zhou X, Lei J, Zhang X, et al: DDX1 methylation mediated MATR3 splicing regulates intervertebral disc degeneration by initiating chromatin reprogramming. Nat Commun. 16:61532025. View Article : Google Scholar : PubMed/NCBI

56 

Wang K, Wu X, Li H, Xu X, Cheng F, Chen J, Zhou H, Xu J, Yu C, Li Y, et al: Mitophagy reprograms lactate metabolism to suppress THBS1 via H3K18la reduction, alleviating intervertebral disc degeneration. Research (Wash D C). 8:09572025.PubMed/NCBI

57 

Zeng Y, Wang S, Gao S, Soares F, Ahmed M, Guo H, Wang M, Hua JT, Guan J, Moran MF, et al: Refined RIP-seq protocol for epitranscriptome analysis with low input materials. PLoS Biol. 16:e20060922018. View Article : Google Scholar : PubMed/NCBI

58 

Dominissini D, Moshitch-Moshkovitz S, Amariglio N and Rechavi G: Transcriptome-wide mapping of N6-methyladenosine by m6A-Seq. Methods Enzymol. 560:131–147. 2015. View Article : Google Scholar : PubMed/NCBI

59 

Körtel N, Rücklé C, Zhou Y, Busch A, Hoch-Kraft P, Sutandy FXR, Haase J, Pradhan M, Musheev M, Ostareck D, et al: Deep and accurate detection of m6A RNA modifications using miCLIP2 and m6Aboost machine learning. Nucleic Acids Res. 49:e922021. View Article : Google Scholar : PubMed/NCBI

60 

Yang Y, Lu Y, Wang Y, Wen X, Qi C, Piao W and Jin H: Current progress in strategies to profile transcriptomic m6A modifications. Front Cell Dev Biol. 12:13921592024. View Article : Google Scholar : PubMed/NCBI

61 

Xia W, Guo L, Su H, Li J, Lu J, Li H and Huang B: A low-cost, low-input method establishment for m6A MeRIP-seq. Biosci Rep. 44:BSR202314302024. View Article : Google Scholar : PubMed/NCBI

62 

Wang Y, Xiao Y, Dong S, Yu Q and Jia G: Antibody-free enzyme-assisted chemical approach for detection of N6-methyladenosine. Nat Chem Biol. 16:896–903. 2020. View Article : Google Scholar : PubMed/NCBI

63 

Zhang LS, Dai Q and He C: Base-resolution sequencing methods for whole-transcriptome quantification of mRNA modifications. Acc Chem Res. 57:47–58. 2024. View Article : Google Scholar : PubMed/NCBI

64 

Liu C, Sun H, Yi Y, Shen W, Li K, Xiao Y, Li F, Li Y, Hou Y, Lu B, et al: Absolute quantification of single-base m6A methylation in the mammalian transcriptome using GLORI. Nat Biotechnol. 41:355–366. 2023. View Article : Google Scholar : PubMed/NCBI

65 

Sun H, Lu B, Zhang Z, Xiao Y, Zhou Z, Xi L, Li Z, Jiang Z, Zhang J, Wang M, et al: Mild and ultrafast GLORI enables absolute quantification of m6A methylome from low-input samples. Nat Methods. 22:1226–1236. 2025. View Article : Google Scholar : PubMed/NCBI

66 

Garcia-Campos MA, Edelheit S, Toth U, Safra M, Shachar R, Viukov S, Winkler R, Nir R, Lasman L, Brandis A, et al: Deciphering the ‘m6A Code’ via antibody-independent quantitative profiling. Cell. 178:731–747.e16. 2019. View Article : Google Scholar : PubMed/NCBI

67 

Capitanchik C, Toolan-Kerr P, Luscombe NM and Ule J: How do you identify m6 A methylation in transcriptomes at high resolution? A comparison of recent datasets. Front Genet. 11:3982020. View Article : Google Scholar : PubMed/NCBI

68 

Meyer KD: DART-seq: An antibody-free method for global m6A detection. Nat Methods. 16:1275–1280. 2019. View Article : Google Scholar : PubMed/NCBI

69 

Tegowski M, Zhu H and Meyer KD: Detecting m6A with in vitro DART-Seq. Methods Mol Biol. 2404:363–374. 2022. View Article : Google Scholar : PubMed/NCBI

70 

Shen J, Zhang Q, Lan Y, Peng Q, Ji Z, Wu Y and Liu H: Identification and characterisation of potential targets for N6-methyladenosine (m6A) modification during intervertebral disc degeneration. Front Biosci (Landmark Ed). 29:4052024. View Article : Google Scholar : PubMed/NCBI

71 

Liu L, Sun H, Zhang Y, Liu C, Zhuang Y, Liu M, Ai X, Long D, Huang B, Li C, et al: Dynamics of N6-methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc. JOR Spine. 7:e13162024. View Article : Google Scholar : PubMed/NCBI

72 

Chen X, Gong W, Shao X, Shi T, Zhang L, Dong J, Shi Y, Shen S, Qin J, Jiang Q and Guo B: METTL3-mediated m6A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression. Ann Rheum Dis. 81:87–99. 2022. View Article : Google Scholar : PubMed/NCBI

73 

Wu O, Jin Y, Zhang Z, Zhou H, Xu W, Chen L, Jones M, Kwan KYH, Gao J, Zhang K, et al: KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m6A modification of ATG4a to promote NPCs senescence and IVDD progression. Bone Res. 12:672024. View Article : Google Scholar : PubMed/NCBI

74 

Sun R, Wu XT, Shi H, Wang F, Gao JW, Wang PY, Xu ZY, Gan WW, Wang YT and Zhang C: Mechanism of FTO-mediated m6A demethylation regulation of YAP1 in nucleus pulposus cell senescence. Mech Ageing Dev. 227:1121012025. View Article : Google Scholar : PubMed/NCBI

75 

Xu X, Shen L, Qu Y, Li D, Zhao X, Wei H and Yue S: Experimental validation and comprehensive analysis of m6A methylation regulators in intervertebral disc degeneration subpopulation classification. Sci Rep. 14:84172024. View Article : Google Scholar : PubMed/NCBI

76 

Guo C, Chen Y, Wang Y and Hao Y: Regulatory roles of noncoding RNAs in intervertebral disc degeneration as potential therapeutic targets (Review). Exp Ther Med. 25:442022. View Article : Google Scholar : PubMed/NCBI

77 

Jiang J, Sun Y, Xu G, Wang H and Wang L: The role of miRNA, lncRNA and circRNA in the development of intervertebral disk degeneration (Review). Exp Ther Med. 21:5552021. View Article : Google Scholar : PubMed/NCBI

78 

Wang C, Cui L, Gu Q, Guo S, Zhu B, Liu X, Li Y, Liu X, Wang D and Li S: The mechanism and function of miRNA in intervertebral disc degeneration. Orthop Surg. 14:463–471. 2022. View Article : Google Scholar : PubMed/NCBI

79 

Li Y, Wang B, Sun W, Kong C, Ding J, Hu F, Li J, Chen X and Lu S: Construction of circ_0071922-miR-15a-5p-mRNA network in intervertebral disc degeneration by RNA-sequencing. JOR Spine. 7:e12752023. View Article : Google Scholar : PubMed/NCBI

80 

Zhao B, Lu M, Wang D, Li H and He X: Genome-wide identification of long noncoding RNAs in human intervertebral disc degeneration by RNA sequencing. Biomed Res Int. 2016:36848752016. View Article : Google Scholar : PubMed/NCBI

81 

Guo ZL, Liu YY, Gao Y, Guan XM, Li H and Cheng M: Circ-RNA expression pattern and circ-RNA-miRNA-mRNA network in the pathogenesis of human intervertebral disc degeneration. Cell J. 23:218–224. 2021.PubMed/NCBI

82 

Wan ZY, Song F, Sun Z, Chen YF, Zhang WL, Samartzis D, Ma CJ, Che L, Liu X, Ali MA, et al: Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: A microarray related study. Arthritis Res Ther. 16:4652014. View Article : Google Scholar : PubMed/NCBI

83 

Cheng X, Zhang L, Zhang K, Zhang G, Hu Y, Sun X, Zhao C, Li H, Li YM and Zhao J: Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein. Ann Rheum Dis. 77:770–779. 2018. View Article : Google Scholar : PubMed/NCBI

84 

Yu C, Zhao J, Cheng F, Chen J, Chen J, Xu H, Shi K, Xia K, Ding S, Wang K, et al: Silencing circATXN1 in aging nucleus pulposus cell alleviates intervertebral disc degeneration via correcting progerin mislocalization. Research (Wash D C). 7:03362024.PubMed/NCBI

85 

Wang T, Yan X, Song D, Li Y, Li Z and Feng D: CircEYA3 aggravates intervertebral disc degeneration through the miR-196a-5p/EBF1 axis and NF-κB signaling. Commun Biol. 7:3902024. View Article : Google Scholar : PubMed/NCBI

86 

Chen X, Song Y, Chen G, Zhang B, Bai Y, Sun C, Fan D and Chen Z: Circular RNA CircFOXO3 functions as a competitive endogenous RNA for acid-sensing ion channel subunit 1 mediating oxeiptosis in nucleus pulposus. Biomedicines. 12:6782024. View Article : Google Scholar : PubMed/NCBI

87 

Ji ML, Jiang H, Zhang XJ, Shi PL, Li C, Wu H, Wu XT, Wang YT, Wang C and Lu J: Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Nat Commun. 9:50512018. View Article : Google Scholar : PubMed/NCBI

88 

Huang Y, Zhang Z, Wang J, Shen S, Yao T, Xu Y, Chen Z, Fang B and Ma J: circSPG21 protects against intervertebral disc disease by targeting miR-1197/ATP1B3. Exp Mol Med. 53:1547–1558. 2021. View Article : Google Scholar : PubMed/NCBI

89 

Du X, Chen S, Cui H, Huang Y, Wang J, Liu H, Li Z, Liang C, Zheng Z and Wang H: Circular RNA hsa_circ_0083756 promotes intervertebral disc degeneration by sponging miR-558 and regulating TREM1 expression. Cell Prolif. 55:e132052022. View Article : Google Scholar : PubMed/NCBI

90 

Xie L, Huang W, Fang Z, Ding F, Zou F, Ma X, Tao J, Guo J, Xia X, Wang H, et al: CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis. Cell Death Dis. 10:7512019. View Article : Google Scholar : PubMed/NCBI

91 

Yao W, Hu X and Wang X: Crossing epigenetic frontiers: The intersection of novel histone modifications and diseases. Signal Transduct Target Ther. 9:2322024. View Article : Google Scholar : PubMed/NCBI

92 

Gu T, He Y, Zhou J, Qiu X, Yang W, Zhu Q, Liang Y, Zheng Y, Yik JHN, Haudenschild DR, et al: CircFUNDC1 interacts with CDK9 to promote mitophagy in nucleus pulposus cells under oxidative stress and ameliorates intervertebral disc degeneration. Cell Death Dis. 16:942025. View Article : Google Scholar : PubMed/NCBI

93 

Guo Z, Su W, Zhou R, Zhang G, Yang S, Wu X, Qiu C, Cong W, Shen N, Guo J, et al: Exosomal MATN3 of urine-derived stem cells ameliorates intervertebral disc degeneration by antisenescence effects and promotes NPC proliferation and ECM synthesis by activating TGF-β. Oxid Med Cell Longev. 2021:55422412021. View Article : Google Scholar : PubMed/NCBI

94 

Wang Z, Zhang J, Zheng W and He Y: Long non-coding RNAs H19 and HOTAIR implicated in intervertebral disc degeneration. Front Genet. 13:8435992022. View Article : Google Scholar : PubMed/NCBI

95 

Yu Y, Zhang X, Li Z, Kong L and Huang Y: LncRNA HOTAIR suppresses TNF-α induced apoptosis of nucleus pulposus cells by regulating miR-34a/Bcl-2 axis. Biomed Pharmacother. 107:729–737. 2018. View Article : Google Scholar : PubMed/NCBI

96 

Shao T, Hu Y, Tang W, Shen H, Yu Z and Gu J: The long noncoding RNA HOTAIR serves as a microRNA-34a-5p sponge to reduce nucleus pulposus cell apoptosis via a NOTCH1-mediated mechanism. Gene. 715:1440292019. View Article : Google Scholar : PubMed/NCBI

97 

Zhang S, Song S, Cui W, Liu X and Sun Z: Mechanism of long noncoding RNA HOTAIR in nucleus pulposus cell autophagy and apoptosis in intervertebral disc degeneration. Evid Based Complement Alternat Med. 2022:85046012022.PubMed/NCBI

98 

Zhan S, Wang K, Song Y, Li S, Yin H, Luo R, Liao Z, Wu X, Zhang Y and Yang C: Long non-coding RNA HOTAIR modulates intervertebral disc degenerative changes via Wnt/β-catenin pathway. Arthritis Res Ther. 21:2012019. View Article : Google Scholar : PubMed/NCBI

99 

Donato L, Mordà D, Scimone C, Alibrandi S, D'Angelo R and Sidoti A: From powerhouse to regulator: The role of mitoepigenetics in mitochondrion-related cellular functions and human diseases. Free Radic Biol Med. 218:105–119. 2024. View Article : Google Scholar : PubMed/NCBI

100 

Hou Y, Liu L, Guo Y and Shi J: Epigenetic crossroads in intervertebral disc degeneration: Unlocking novel therapeutic avenues (Review). Mol Med Rep. 33:1132026. View Article : Google Scholar : PubMed/NCBI

101 

Wiese M and Bannister AJ: Two genomes, one cell: Mitochondrial-nuclear coordination via epigenetic pathways. Mol Metab. 38:1009422020. View Article : Google Scholar : PubMed/NCBI

102 

Cao K, Feng Z, Gao F, Zang W and Liu J: Mitoepigenetics: An intriguing regulatory layer in aging and metabolic-related diseases. Free Radic Biol Med. 177:337–346. 2021. View Article : Google Scholar : PubMed/NCBI

103 

Sharma J, Kumari R, Bhargava A, Tiwari R and Mishra PK: Mitochondrial-induced epigenetic modifications: From biology to clinical translation. Curr Pharm Des. 27:159–176. 2021. View Article : Google Scholar : PubMed/NCBI

104 

Matilainen O, Quirós PM and Auwerx J: Mitochondria and epigenetics-crosstalk in homeostasis and stress. Trends Cell Biol. 27:453–463. 2017. View Article : Google Scholar : PubMed/NCBI

105 

Yin MT and Guo L: Mitochondrial DNA methylation: State-of-the-art in molecular mechanisms and disease implications. J Adv Res. 83:455–473. 2026. View Article : Google Scholar : PubMed/NCBI

106 

Shock LS, Thakkar PV, Robinson JM and Taylor SM: Cytosine methylase and hydroxymethylase activity in mammalian mitochondria. Front Cell Dev Biol. 13:16774022025. View Article : Google Scholar : PubMed/NCBI

107 

Santos JH: Mitochondria signaling to the epigenome: A novel role for an old organelle. Free Radic Biol Med. 170:59–69. 2021. View Article : Google Scholar : PubMed/NCBI

108 

Liu YF, Zhu JJ, Yu Tian X, Liu H, Zhang T, Zhang YP, Xie SA, Zheng M, Kong W, Yao WJ, et al: Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility. Cell Death Dis. 11:352020. View Article : Google Scholar : PubMed/NCBI

109 

Coppedè F and Stoccoro A: Mitoepigenetics and neurodegenerative diseases. Front Endocrinol (Lausanne). 10:862019. View Article : Google Scholar : PubMed/NCBI

110 

Mishra M and Kowluru RA: Epigenetic modification of mitochondrial DNA in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 56:5133–5142. 2015. View Article : Google Scholar : PubMed/NCBI

111 

Zhang J, Shang J, Wang F, Huo X, Sun R, Ren Z, Wang W, Yang M, Li G, Gao D, et al: Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL. Clin Epigenetics. 14:22022. View Article : Google Scholar : PubMed/NCBI

112 

Hu X, Wang Z, Zhang H, Cui P, Li Y, Chen X, Kong C, Wang W and Lu S: Single-cell sequencing: New insights for intervertebral disc degeneration. Biomed Pharmacother. 165:1152242023. View Article : Google Scholar : PubMed/NCBI

113 

Yu C, Yang W, Wang Y and Zhang Y: Single-cell sequencing reveals key biological insights into intervertebral disc development and degeneration. Curr Mol Med. Jan 13–2026.(Epub ahead of print). View Article : Google Scholar

114 

Yang G, Dong C, Wu Z, Wu P, Yang C, Li L, Zhang J and Wu X: Single-cell RNA sequencing-guided engineering of mitochondrial therapies for intervertebral disc degeneration by regulating mtDNA/SPARC-STING signaling. Bioact Mater. 48:564–582. 2025.PubMed/NCBI

115 

Zhao L, Liang K, Cheng W, Zhou X, Yang L, Mao X, Qi W, Jin H, Zhang W, Pan H and Wang D: A multifaceted strategy for intra- and extracellular nucleic acid regulation to alleviate intervertebral disc degeneration. Nat Commun. 16:79362025. View Article : Google Scholar : PubMed/NCBI

116 

Zhou H, Liang C, Cheng F, Wang K, Zhang Y, Chen J, Xu H, Yu C, Xia K, Li Y, et al: Mitochondria-targeting polymeric micelles for intervertebral disc degeneration alleviation via coordinated cascade energetic intervention. ACS Nano. 19:41121–41135. 2025. View Article : Google Scholar : PubMed/NCBI

117 

Fu J, Leng X, Long J, Liao Z, An X, Ai X, Long D, Li C, Huang B, Zhou Y, et al: SETD1A regulates glycolysis and senescence of nucleus pulposus cells via H3K4me3-HELZ2/PPARα-HIF1α axis to drive intervertebral disc degeneration. Adv Sci (Weinh). e751052026.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

118 

Wu O, Jin Y, Weng S, Zhang Z, Tu K, Sun J, Chen L, Chen Q, Chen Z, Jones M, et al: METTL3 regulates α-KG-dependent mitophagy and apoptosis in nucleus pulposus cells through the MALAT1/miR-23c/IDH1 axis. Cell Rep. 45:1167932026. View Article : Google Scholar : PubMed/NCBI

119 

Yao B, Wan L, Deng J, Chen Z, Zhao L, Wang W and Han Z: m6A-mediated silencing of RNF41 by METTL3/YTHDC1 disrupts autophagy to drive intervertebral disc degeneration. Cell Biol Toxicol. 41:1472025. View Article : Google Scholar : PubMed/NCBI

120 

Yang Q, Huang F, Wang C, Liang X, Huang L, Xu H, Liu J, Wei Q and Jiang H: METTL3-mediated m6A modification promotes intervertebral disc degeneration. Ann Med. 57:25466702025. View Article : Google Scholar : PubMed/NCBI

121 

Song C, Xu Y, Peng Q, Chen R, Zhou D, Cheng K, Cai W, Liu T, Huang C, Fu Z, et al: Mitochondrial dysfunction: A new molecular mechanism of intervertebral disc degeneration. Inflamm Res. 72:2249–2260. 2023. View Article : Google Scholar : PubMed/NCBI

122 

Qiu B, Xie X and Xi Y: Mitochondrial quality control: The real dawn of intervertebral disc degeneration? J Transl Med. 22:11262024. View Article : Google Scholar : PubMed/NCBI

123 

Song Y, Liang H, Li G, Ma L, Zhu D, Zhang W, Tong B, Li S, Gao Y, Wu X, et al: The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn2+ trafficking. Autophagy. 20:809–829. 2024. View Article : Google Scholar : PubMed/NCBI

124 

Liu M, Liu K, Cheng D, Zheng B, Li S and Mo Z: The regulatory role of NLRX1 in innate immunity and human disease. Cytokine. 160:1560552022. View Article : Google Scholar : PubMed/NCBI

125 

Stokman G, Kors L, Bakker PJ, Rampanelli E, Claessen N, Teske GJD, Butter L, van Andel H, van den Bergh Weerman MA, Larsen PWB, et al: NLRX1 dampens oxidative stress and apoptosis in tissue injury via control of mitochondrial activity. J Exp Med. 214:2405–2420. 2017. View Article : Google Scholar : PubMed/NCBI

126 

Roth GV, Gengaro IR and Qi LS: Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications. Cell Chem Biol. S2451-9456(24)00309-X. 2024.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

127 

Yuan L, Xiong Y, Zhang Y, Gu S and Lei Y: Epigenome editing based treatment: Progresses and challenges. Mol Ther. 34:46–67. 2026. View Article : Google Scholar : PubMed/NCBI

128 

Cappelluti MA, Mollica Poeta V, Valsoni S, Quarato P, Merlin S, Merelli I and Lombardo A: Durable and efficient gene silencing in vivo by hit-and-run epigenome editing. Nature. 627:416–423. 2024. View Article : Google Scholar : PubMed/NCBI

129 

Kantor B, O'Donovan B, Rittiner J, Hodgson D, Lindner N, Guerrero S, Dong W, Zhang A and Chiba-Falek O: The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders. Nat Commun. 15:72592024. View Article : Google Scholar : PubMed/NCBI

130 

Lei Y, Zhang X, Su J, Jeong M, Gundry MC, Huang YH, Zhou Y, Li W and Goodell MA: Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein. Nat Commun. 8:160262017. View Article : Google Scholar : PubMed/NCBI

131 

Horii T, Morita S, Hino S, Kimura M, Hino Y, Kogo H, Nakao M and Hatada I: Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome. Genome Biol. 21:772020. View Article : Google Scholar : PubMed/NCBI

132 

Stover JD, Trone MA, Lawrence B and Bowles RD: Multiplex epigenome editing of ion channel expression in nociceptive neurons abolished degenerative IVD-conditioned media-induced mechanical sensitivity. JOR Spine. 6:e12532023. View Article : Google Scholar : PubMed/NCBI

133 

Stover JD, Farhang N, Lawrence B and Bowles RD: Multiplex epigenome editing of dorsal root ganglion neuron receptors abolishes redundant interleukin 6, tumor necrosis factor alpha, and interleukin 1β signaling by the degenerative intervertebral disc. Hum Gene Ther. 30:1147–1160. 2019. View Article : Google Scholar : PubMed/NCBI

134 

Stover JD, Trone MAR, Weston J, Lewis C, Levis H, Farhang N, Philippi M, Zeidan M, Lawrence B and Bowles RD: Therapeutic CRISPR epigenome editing of inflammatory receptors in the intervertebral disc. Mol Ther. 32:3955–3973. 2024. View Article : Google Scholar : PubMed/NCBI

135 

Liang T, Gao B, Zhou J, Qiu X, Qiu J, Chen T, Liang Y, Gao W, Qiu X and Lin Y: Constructing intervertebral disc degeneration animal model: A review of current models. Front Surg. 9:10892442023. View Article : Google Scholar : PubMed/NCBI

136 

Tang SN, Bonilla AF, Chahine NO, Colbath AC, Easley JT, Grad S, Haglund L, Le Maitre CL, Leung V, McCoy AM, et al: Controversies in spine research: Organ culture versus in vivo models for studies of the intervertebral disc. JOR Spine. 5:e12352022. View Article : Google Scholar : PubMed/NCBI

137 

Daly C, Ghosh P, Jenkin G, Oehme D and Goldschlager T: A review of animal models of intervertebral disc degeneration: Pathophysiology, regeneration, and translation to the clinic. Biomed Res Int. 2016:59521652016. View Article : Google Scholar : PubMed/NCBI

138 

Choi H, Tessier S, Silagi ES, Kyada R, Yousefi F, Pleshko N, Shapiro IM and Risbud MV: A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis. Matrix Biol. 70:102–122. 2018. View Article : Google Scholar : PubMed/NCBI

139 

Bergknut N, Rutges JPHJ, Kranenburg HJC, Smolders LA, Hagman R, Smidt HJ, Lagerstedt AS, Penning LC, Voorhout G, Hazewinkel HAW, et al: The dog as an animal model for intervertebral disc degeneration? Spine (Phila Pa 1976). 37:351–358. 2012. View Article : Google Scholar : PubMed/NCBI

140 

Xu X, Wang D, Zheng C, Gao B, Fan J, Cheng P, Liu B, Yang L and Luo Z: Progerin accumulation in nucleus pulposus cells impairs mitochondrial function and induces intervertebral disc degeneration and therapeutic effects of sulforaphane. Theranostics. 9:2252–2267. 2019. View Article : Google Scholar : PubMed/NCBI

141 

Castillo ER and Lieberman DE: Lower back pain. Evol Med Public Health. 2015:2–3. 2015. View Article : Google Scholar : PubMed/NCBI

142 

Alini M, Diwan AD, Erwin WM, Little CB and Melrose J: An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics. JOR Spine. 6:e12302023. View Article : Google Scholar : PubMed/NCBI

143 

Kong M, Gao C, Han S, Jin C, Hao M, Zhao J, Luan J, Lin Y, Li Q and Ma X: Establishing an intervertebral disc degeneration model in bipedal rats via a modified feeding approach. Sci Rep. 15:353192025. View Article : Google Scholar : PubMed/NCBI

144 

Cheng Y, Ma Z, Kim BH, Wu W, Cayting P, Boyle AP, Sundaram V, Xing X, Dogan N, Li J, et al: Principles of regulatory information conservation between mouse and human. Nature. 515:371–375. 2014. View Article : Google Scholar : PubMed/NCBI

145 

Mainardi A, Cambria E, Occhetta P, Martin I, Barbero A, Schären S, Mehrkens A and Krupkova O: Intervertebral disc-on-a-chip as advanced in vitro model for mechanobiology research and drug testing: A review and perspective. Front Bioeng Biotechnol. 9:8268672022. View Article : Google Scholar : PubMed/NCBI

146 

Poletto DL, Crowley JD, Tanglay O, Walsh WR and Pelletier MH: Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review. JOR Spine. 6:e12342022. View Article : Google Scholar : PubMed/NCBI

147 

Romaniyanto F, Mahyudin F, Utomo DN, Suroto H, Sari WA, Fachreza MS, Sadewa D, Dzikri DN and Nofaldi F: Effectivity of puncture method for intervertebral disc degeneration animal models: Review article. Ann Med Surg (Lond). 85:3501–3505. 2023. View Article : Google Scholar : PubMed/NCBI

148 

Sakai D and Grad S: Advancing the cellular and molecular therapy for intervertebral disc disease. Adv Drug Deliv Rev. 84:159–171. 2015. View Article : Google Scholar : PubMed/NCBI

149 

ENCODE Project Consortium, . Moore JE, Purcaro MJ, Pratt HE, Epstein CB, Shoresh N, Adrian J, Kawli T, Davis CA, Dobin A, et al: Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature. 583:699–710. 2020. View Article : Google Scholar : PubMed/NCBI

150 

Zhou H, Clark E, Guan D, Lagarrigue S, Fang L, Cheng H, Tuggle CK, Kapoor M, Wang Y, Giuffra E and Egidy G: Comparative genomics and epigenomics of transcriptional regulation. Annu Rev Anim Biosci. 13:73–98. 2025. View Article : Google Scholar : PubMed/NCBI

151 

Hao Y, Zhu G, Yu L, Ren Z, Zhou W, Zhang P and Lian X: FOXO3-activated HOTTIP sequesters miR-615-3p away from COL2A1 to mitigate intervertebral disc degeneration. Am J Pathol. 194:280–295. 2024. View Article : Google Scholar : PubMed/NCBI

152 

Jiang X and Chen D: LncRNA FAM83H-AS1 maintains intervertebral disc tissue homeostasis and attenuates inflammation-related pain via promoting nucleus pulposus cell growth through miR-22-3p inhibition. Ann Transl Med. 8:15182020. View Article : Google Scholar : PubMed/NCBI

153 

Yang X, Cao X, Wang X, Guo J, Yang Y, Lu L, Zhang P, Yang H, Rong K, Zhou T, et al: Palladium nanoparticles degrade advanced glycation end products via valosin-containing protein mediated autophagy to attenuate high-glucose/high-fat-induced intervertebral disc degeneration. Exploration (Beijing). 5:202301742025. View Article : Google Scholar : PubMed/NCBI

154 

Kawarai Y, Jang SH, Lee S, Millecamps M, Kang H, Gregoire S, Suzuki-Narita M, Ohtori S and Stone LS: Exercise attenuates low back pain and alters epigenetic regulation in intervertebral discs in a mouse model. Spine J. 21:1938–1949. 2021. View Article : Google Scholar : PubMed/NCBI

155 

Zhang Z, Lin J, Nisar M, Chen T, Xu T, Zheng G, Wang C, Jin H, Chen J, Gao W, et al: The Sirt1/P53 axis in diabetic intervertebral disc degeneration pathogenesis and therapeutics. Oxid Med Cell Longev. 2019:79595732019.PubMed/NCBI

156 

Zhang TW, Li ZF, Dong J and Jiang LB: The circadian rhythm in intervertebral disc degeneration: An autophagy connection. Exp Mol Med. 52:31–40. 2020. View Article : Google Scholar : PubMed/NCBI

157 

Dudek M, Gossan N, Yang N, Im HJ, Ruckshanthi JP, Yoshitane H, Li X, Jin D, Wang P, Boudiffa M, et al: The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. J Clin Invest. 126:365–376. 2016. View Article : Google Scholar : PubMed/NCBI

158 

Xiang M, Peng Q, Dai F, Wu Y, Liu L and Liu H: Machine learning-enabled identification of nucleus pulposus senescence-associated genes as potential biomarkers for intervertebral disc degeneration. Eur J Med Res. 30:8872025. View Article : Google Scholar : PubMed/NCBI

159 

Huang K, Shen L, Guan H, Dai L, Huang X, Zhang X, Xu X and Liu C: Construction of a lncRNA-miRNA-mRNA network for biomarker identification in intervertebral disc degeneration. J Musculoskelet Neuronal Interact. 25:316–327. 2025. View Article : Google Scholar : PubMed/NCBI

160 

Murphy K, Lufkin T and Kraus P: Development and degeneration of the intervertebral disc-insights from across species. Vet Sci. 10:5402023.PubMed/NCBI

161 

Hu Y, Yang R, Liu S, Song Z and Wang H: The emerging roles of nanocarrier drug delivery system in treatment of intervertebral disc degeneration-current knowledge, hot spots, challenges and future perspectives. Drug Des Devel Ther. 18:1007–1022. 2024. View Article : Google Scholar : PubMed/NCBI

162 

Ding Y, Li F, Wang Y, Pan W, Fu X and Tan S: Nanomedicine approaches for intervertebral disc regeneration: From bench to bedside. Pharmaceutics. 17:3132025. View Article : Google Scholar : PubMed/NCBI

163 

Wagner EK, Vedadghavami A, Jacobsen TD, Goel SA, Chahine NO and Bajpayee AG: Avidin grafted dextran nanostructure enables a month-long intra-discal retention. Sci Rep. 10:120172020. View Article : Google Scholar : PubMed/NCBI

164 

Zhou H, Ning H, Liu Q, Tan Q, Zeng D, Feng X, Wang D, Zhao Q, Wu X, He H, et al: A single-cell-inspired self-enrichment therapeutic strategy delays intervertebral disc degeneration by inhibiting pyroptosis. Adv Mater. 38:e164052026. View Article : Google Scholar : PubMed/NCBI

165 

Wang Y, Wu Y, Zhang B, Zheng C, Hu C, Guo C, Kong Q and Wang Y: Repair of degenerative nucleus pulposus by polyphenol nanosphere-encapsulated hydrogel gene delivery system. Biomaterials. 298:1221322023. View Article : Google Scholar : PubMed/NCBI

166 

Wang Y, Deng M, Wu Y, Zheng C, Zhang F, Guo C, Zhang B, Hu C, Kong Q and Wang Y: A multifunctional mitochondria-protective gene delivery platform promote intervertebral disc regeneration. Biomaterials. 317:1230672025. View Article : Google Scholar : PubMed/NCBI

167 

Shi S, Ou X, Liu C, Li R, Zheng Q and Hu L: Nanotechnology-enhanced pharmacotherapy for intervertebral disc degeneration treatment. Int J Nanomedicine. 19:14043–14058. 2024. View Article : Google Scholar : PubMed/NCBI

168 

Yang L, Bhujel B, Hou Y, Luo J, An SB, Han I and Lee KB: Effective modulation of inflammation and oxidative stress for enhanced regeneration of intervertebral discs using 3D porous hybrid protein nanoscaffold. Adv Mater. 35:e23030212023. View Article : Google Scholar : PubMed/NCBI

169 

Guo C, Liu Y, Zhao Z, Wu Y, Kong Q and Wang Y: Regulating inflammation and apoptosis: A smart microgel gene delivery system for repairing degenerative nucleus pulposus. J Control Release. 365:1004–1018. 2024. View Article : Google Scholar : PubMed/NCBI

170 

Chen Z, Liao Z, Liu M, Lin F, Chen S, Wang G, Zheng Z, Liu B, Li C, Wang Z, et al: Nucleus pulposus-targeting nanocarriers facilitate mirna-based therapeutics for intervertebral disc degeneration. Adv Healthc Mater. 12:e23013372023. View Article : Google Scholar : PubMed/NCBI

171 

Song T, Chen H, Huang J, Tian Y, Zhang X, Chen H, Xie Y and Chen L: Engineering nanomaterials for the treatment of intervertebral disc degeneration: From application to therapeutic mechanisms. Small. 21:e098062025. View Article : Google Scholar : PubMed/NCBI

172 

Liu W, Ma Z, Wang Y and Yang J: Multiple nano-drug delivery systems for intervertebral disc degeneration: Current status and future perspectives. Bioact Mater. 23:274–299. 2022.PubMed/NCBI

173 

Bailey JF, Fields AJ, Liebenberg E, Mattison JA, Lotz JC and Kramer PA: Comparison of vertebral and intervertebral disc lesions in aging humans and rhesus monkeys. Osteoarthritis Cartilage. 22:980–985. 2014. View Article : Google Scholar : PubMed/NCBI

174 

Thompson K, Moore S, Tang S, Wiet M and Purmessur D: The chondrodystrophic dog: A clinically relevant intermediate-sized animal model for the study of intervertebral disc-associated spinal pain. JOR Spine. 1:e10112018. View Article : Google Scholar : PubMed/NCBI

175 

Gruber HE and Hanley EN Jr: Morphologic features of spontaneous annular tears and disc degeneration in the aging sand rat (Psammomys obesus obesus). Biotech Histochem. 92:402–410. 2017. View Article : Google Scholar : PubMed/NCBI

176 

Tabatabaei SF, Akbari Roknabadi S and Koohi S: DeepEPI: CNN-transformer-based model for extracting TF interactions through predicting enhancer-promoter interactions. Bioinform Adv. 5:vbaf2212025. View Article : Google Scholar : PubMed/NCBI

177 

Ahmed FS, Aly S and Liu X: EPI-Trans: An effective transformer-based deep learning model for enhancer promoter interaction prediction. BMC Bioinformatics. 25:2162024. View Article : Google Scholar : PubMed/NCBI

178 

Yan Y, Chai X, Liu J, Wang S, Li W and Huang T: DeepMethyGene: A deep-learning model to predict gene expression using DNA methylations. BMC Bioinformatics. 26:992025. View Article : Google Scholar : PubMed/NCBI

179 

Zhang A, Jia J, Sun M and Wei X: EPI-DynFusion: Enhancer-promoter interaction prediction model based on sequence features and dynamic fusion mechanisms. Front Genet. 16:16142222025. View Article : Google Scholar : PubMed/NCBI

180 

Zhang T, Shao S, Zhang H, Zhao Z, Zhao X, Zhang X, Wang Z and Wang G: KansformerEPI: A deep learning framework integrating KAN and transformer for predicting enhancer-promoter interactions. Brief Bioinform. 26:bbaf2722025. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cui X, Zeng L, Zhang W, Xi L, Wang R, Jia D, Safa , Feng H and Jia H: Epigenetic research methods and animal models for intervertebral disc degeneration (Review). Mol Med Rep 34: 203, 2026.
APA
Cui, X., Zeng, L., Zhang, W., Xi, L., Wang, R., Jia, D. ... Jia, H. (2026). Epigenetic research methods and animal models for intervertebral disc degeneration (Review). Molecular Medicine Reports, 34, 203. https://doi.org/10.3892/mmr.2026.13913
MLA
Cui, X., Zeng, L., Zhang, W., Xi, L., Wang, R., Jia, D., Safa, , Feng, H., Jia, H."Epigenetic research methods and animal models for intervertebral disc degeneration (Review)". Molecular Medicine Reports 34.1 (2026): 203.
Chicago
Cui, X., Zeng, L., Zhang, W., Xi, L., Wang, R., Jia, D., Safa, , Feng, H., Jia, H."Epigenetic research methods and animal models for intervertebral disc degeneration (Review)". Molecular Medicine Reports 34, no. 1 (2026): 203. https://doi.org/10.3892/mmr.2026.13913
Copy and paste a formatted citation
x
Spandidos Publications style
Cui X, Zeng L, Zhang W, Xi L, Wang R, Jia D, Safa , Feng H and Jia H: Epigenetic research methods and animal models for intervertebral disc degeneration (Review). Mol Med Rep 34: 203, 2026.
APA
Cui, X., Zeng, L., Zhang, W., Xi, L., Wang, R., Jia, D. ... Jia, H. (2026). Epigenetic research methods and animal models for intervertebral disc degeneration (Review). Molecular Medicine Reports, 34, 203. https://doi.org/10.3892/mmr.2026.13913
MLA
Cui, X., Zeng, L., Zhang, W., Xi, L., Wang, R., Jia, D., Safa, , Feng, H., Jia, H."Epigenetic research methods and animal models for intervertebral disc degeneration (Review)". Molecular Medicine Reports 34.1 (2026): 203.
Chicago
Cui, X., Zeng, L., Zhang, W., Xi, L., Wang, R., Jia, D., Safa, , Feng, H., Jia, H."Epigenetic research methods and animal models for intervertebral disc degeneration (Review)". Molecular Medicine Reports 34, no. 1 (2026): 203. https://doi.org/10.3892/mmr.2026.13913
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