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Review
. 2025 Jun 26:18:3217-3261.
doi: 10.2147/JPR.S517224. eCollection 2025.

Epigenetics and Herbs: Potential Therapeutic Strategies for Osteoarthritis of the Knee

Yihui Zheng  1 , Jiahui Wang  1 , Lei Wang  1 , Yang Zheng #  1 , Wen Qi #  1
Affiliations
Review

Epigenetics and Herbs: Potential Therapeutic Strategies for Osteoarthritis of the Knee

Yihui Zheng et al. J Pain Res. .

Abstract

Knee osteoarthritis (KOA) is a complex joint disease characterized by progressive cartilage degeneration with programmed cell death of chondrocytes. Programmed cell death (PCD) of chondrocytes plays a central role in the development of knee osteoarthritis, and epigenetics provides new explanations for this complex biological process. By regulating DNA methylation, histone modification and non-coding RNA, epigenetic mechanisms can significantly affect chondrocyte survival and apoptosis without altering the gene sequence. Recent studies have found that TCM can intervene in the epigenetic regulatory network by targeting epigenetic enzymes with active ingredients, non-coding RNA-mediated co-regulation, and epigenetic-metabolic reprogramming. In this paper, we review the latest studies on epigenetics in chondrocyte programmed cell death, focusing on the mechanisms of DNA methylation, histone modification, and non-coding RNAs, such as miRNAs and lncRNAs, and also discuss the interventional roles of TCM in this process, providing therapeutic references to delve into the pathogenesis of KOA.

Keywords: chondrocytes; epigenetics; knee osteoarthritis; programmed death; traditional Chinese medicine.

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Conflict of interest statement

All authors declare no financial or non-financial conflicts of interest related to the materials or methods described in this manuscript. The product/therapy mentioned in this study is cited for academic purposes only, and no endorsement or commercial association should be inferred.

Figures

None
Graphical abstract
Figure 1
Figure 1
Epigenetic overview diagram, (A) DNA methylation mechanism, (B) RNA methylation mechanism, (C) the mechanism of histone acetylation, (D) mechanism of histone methylation, (E) miRNA transcription process, (F) lncRNA transcription process. By Figdraw.
Figure 2
Figure 2
Diagram of the molecular mechanisms by which DNA methylation, RNA methylation, histone modification, and non-coding RNA modification regulate chondrocyte Apoptosis, (A) Mechanisms by which DNA methylation regulates Apoptosis in chondrocytes, (B) Mechanisms by which RNA methylation regulates Apoptosis in chondrocytes, (C) Mechanisms by which histone modification regulates Apoptosis in chondrocytes, (D) Mechanisms by which non-coding RNA modification regulates Apoptosis in chondrocytes. By FIgdraw.
Figure 3
Figure 3
Diagram of the molecular mechanisms by which DNA methylation, RNA methylation, histone modification, and non-coding RNA modification regulate chondrocyte pyroptosis, (A) Mechanisms by which DNA methylation regulates Pyroptosis in chondrocytes, (B) Mechanisms by which RNA methylation regulates Pyroptosis in chondrocytes, (C) Mechanisms by which histone modification regulates Pyroptosis in chondrocytes, (D) Mechanisms by which non-coding RNA modification regulates Pyroptosis in chondrocytes. By Figdraw.
Figure 4
Figure 4
Diagram of the molecular mechanisms by which DNA methylation, RNA methylation, histone modification, and non-coding RNA modification regulate chondrocyte autophagy, (A) Mechanisms by which DNA methylation regulates autophagy in chondrocytes, (B) Mechanisms by which RNA methylation regulates autophagy in chondrocytes, (C) Mechanisms by which histone modification regulates autophagy in chondrocytes, (D) Mechanisms by which non-coding RNA modification regulates autophagy in chondrocytes. By Figdraw.
Figure 5
Figure 5
Diagram of the molecular mechanisms by which DNA methylation, RNA methylation, histone modifications, and non-coding RNA modifications regulate chondrocyte ferroptosis, (A) Mechanisms by which DNA methylation regulates ferroptosis in chondrocytes, (B) Mechanisms by which RNA methylation regulates ferroptosis in chondrocytes, (C) Mechanisms by which histone modification regulates ferroptosis in chondrocytes, (D) Mechanisms by which non-coding RNA modification regulates ferroptosis in chondrocytes. By Figdraw.
Figure 6
Figure 6
Diagram of the molecular mechanisms by which RNA methylation and non-coding RNA modifications regulate chondrocyte Cuproptosis and Necroptosis, (A) Mechanisms by which RNA methylation regulates Cuproptosis in chondrocytes, (B) Mechanisms by which RNA methylation regulates Necroptosis in chondrocytes, (C) Mechanisms by which non-coding RNA modification regulates Cuproptosis in chondrocytes, (D) Mechanisms by which non-coding RNA modification regulates Necroptosis in chondrocytes. By Figdraw.
Figure 7
Figure 7
Diagram of the molecular mechanism by which monomers regulate PCD in KOA chondrocytes. By Figdraw.
Figure 8
Figure 8
Diagram of the molecular mechanism of complex regulation of KOA chondrocytes. By Figdraw.
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