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International Journal of Frontiers in Medicine, 2023, 5(7); doi: 10.25236/IJFM.2023.050702.

Research progress on epigenetic modification of genes in degenerative osteoarthritis


Li Xiyong1, Liao Changsheng1, Li Songfeng1, Han Pengfei2

Corresponding Author:
Han Pengfei

1Department of Graduate School, Graduate Student Department of Changzhi Medical College, Changzhi, China

2Department of Orthopaedics, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China


Degenerative osteoarthritis is one of the most common joint diseases, and its main pathological manifestations are joint synovitis, subchondral osteosclerosis, progressive damage to cartilage leading to osteophyte formation, and narrowing of joint spaces. A large number of studies have found a certain association between the pathogenesis of different pathological manifestations of OA, but the detailed pathogenesis is still not completely clear. Although the basic cell types of bone and cartilage tissue may all come from aquatic vertebral organisms, it has been found that osteoarthritis is mediated by epigenetic modifications of conserved developmental genes in response to excessive mechanical stress (among other factors), such as epigenetic modifications regulated by microRNAs that maintain the order of morphogenesis and temporal changes in response to stress rather than pathological phenotypes resulting from genetic mutations or new signaling pathways.


Epigenetics, Genes, MicroRNAs, Osteoarthritis

Cite This Paper

Li Xiyong, Liao Changsheng, Li Songfeng, Han Pengfei. Research progress on epigenetic modification of genes in degenerative osteoarthritis. International Journal of Frontiers in Medicine (2023), Vol. 5, Issue 7: 7-12. https://doi.org/10.25236/IJFM.2023.050702.


[1] Godivier, J., Lawrence, E. A., Wang, M., Hammond, C. L., & Nowlan, N. C. (2022). Growth orientations, rather than heterogeneous growth rates, dominate jaw joint morphogenesis in the larval zebrafish. Journal of Anatomy, 241(2), 358–371. https://doi.org/10.1111/joa.13680

[2] Abramoff, B., & Caldera, F. E. (2020). Osteoarthritis: Pathology, Diagnosis, and Treatment Options. The Medical Clinics of North America, 104(2), 293–311. https://doi.org/10.1016/j.mcna.2019.10.007

[3] Cheng, H. W., Chik, T. K., Weir, J., & Chan, B. P. (2022). Differentiation of equine mesenchymal stem cells into cells of osteochondral lineage: potential for osteochondral tissue engineering. Biomedical Materials (Bristol, England), 17(6). https://doi.org/10.1088/1748-605X/ac8c76

[4] van Meurs, J. B., Boer, C. G., Lopez-Delgado, L., & Riancho, J. A. (2019). Role of Epigenomics in Bone and Cartilage Disease. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research, 34(2), 215–230. https://doi.org/10.1002/jbmr.3662

[5] Martel-Pelletier, J., Barr, A. J., Cicuttini, F. M., Conaghan, P. G., Cooper, C., Goldring, M. B., … Pelletier, J.-P. (2016). Osteoarthritis. Nature Reviews. Disease Primers, 2, 16072. https: // doi. org/ 10. 1038/ nrdp.2016.72

[6] Ij, W., S, W., Dt, F., Rd, J., Kt, W., H, M., … De, L. (2017). Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proceedings of the National Academy of Sciences of the United States of America, 114(35). https://doi.org/10.1073/pnas.1703856114

[7] Dj, H., & S, B.-Z. (2019). Osteoarthritis. Lancet (London, England), 393(10182). https://doi. org/10.1016/S0140-6736(19)30417-9

[8] G, P., & Mj, T. (2021). Osteoarthritis year in review 2020: epidemiology & therapy. Osteoarthritis and cartilage, 29(2). https://doi.org/10.1016/j.joca.2020.10.007

[9] Sx, W., Ax, G., A, B., Jk, M., Wm, R., & D, M. (2017). Healthcare resource utilization and costs by age and joint location among osteoarthritis patients in a privately insured population. Journal of medical economics, 20(12). https://doi.org/10.1080/13696998.2017.1377717

[10] Mobasheri, A., & Batt, M. (2016). An update on the pathophysiology of osteoarthritis. Annals of Physical and Rehabilitation Medicine, 59(5–6), 333–339. https://doi.org/10.1016/j.rehab.2016.07.004

[11] Millerand, M., Berenbaum, F., & Jacques, C. (2019). Danger signals and inflammaging in osteoarthritis. Clinical and Experimental Rheumatology, 37 Suppl 120(5), 48–56.

[12] McKay, C. D., Cumming, S. P., & Blake, T. (2019). Youth sport: Friend or Foe? Best Practice & Research. Clinical Rheumatology, 33(1), 141–157. https://doi.org/10.1016/j.berh.2019.01.017

[13] Hügle, T., & Geurts, J. (2017). What drives osteoarthritis?-synovial versus subchondral bone pathology. Rheumatology (Oxford, England), 56(9), 1461–1471. https: // doi. org/ 10. 1093/ rheumatology/ kew389

[14] Segarra-Queralt, M., Piella, G., & Noailly, J. (2023). Network-based modelling of mechano-inflammatory chondrocyte regulation in early osteoarthritis. Frontiers in Bioengineering and Biotechnology, 11, 1006066. https://doi.org/10.3389/fbioe.2023.1006066

[15] Aho, O.-M., Finnilä, M., Thevenot, J., Saarakkala, S., & Lehenkari, P. (2017). Subchondral bone histology and grading in osteoarthritis. PloS One, 12(3), e0173726. https: // doi. org/ 10. 1371/ journal. pone. 0173726

[16] Mathiessen, A., & Conaghan, P. G. (2017). Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Research & Therapy, 19(1), 18. https://doi.org/10.1186/s13075-017-1229-9

[17] B, K., E, V., & Ee, N. (2019). Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis. International journal of molecular sciences, 20(18). https://doi.org/10.3390/ijms20184653

[18] Aj, K., Ec, F., Om, E., L, L., Lm, J., Pm, R., … T, M. (2023). Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 in osteoarthritis. Annals of the rheumatic diseases, 82(2). https://doi.org/10.1136/ard-2022-222773

[19] Hi, R., N, Y., Ks, C., S, T., Nm, C., Ro, O., … F, B. (2005). Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis and rheumatism, 52(10). https: // doi. org/ 10. 1002/ art. 21300

[20] Iliopoulos, D., Malizos, K. N., & Tsezou, A. (2007). Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Annals of the Rheumatic Diseases, 66(12), 1616–1621. https: // doi. org/ 10. 1136/ ard. 2007. 069377

[21] Shen, J., Wang, C., Li, D., Xu, T., Myers, J., Ashton, J. M., … O’Keefe, R. J. (2017). DNA methyltransferase 3b regulates articular cartilage homeostasis by altering metabolism. JCI insight, 2(12), e93612, 93612. https://doi.org/10.1172/jci.insight.93612

[22] Gu, X., Li, F., Gao, Y., Che, X., & Li, P. (2022). HDAC4 mutant represses chondrocyte hypertrophy by locating in the nucleus and attenuates disease progression of posttraumatic osteoarthritis. BMC musculoskeletal disorders, 23(1), 8. https://doi.org/10.1186/s12891-021-04947-6

[23] Tx, L., & Me, R. (2018). MicroRNA. The Journal of allergy and clinical immunology, 141(4). https://doi.org/10.1016/j.jaci.2017.08.034

[24] Swingler, T. E., Niu, L., Smith, P., Paddy, P., Le, L., Barter, M. J., … Clark, I. M. (2019). The function of microRNAs in cartilage and osteoarthritis. Clinical and Experimental Rheumatology, 37 Suppl 120(5), 40–47.

[25] Zhang, M., Lygrisse, K., & Wang, J. (2017). Role of MicroRNA in Osteoarthritis. Journal of Arthritis, 6(2), 239. https://doi.org/10.4172/2167-7921.1000239

[26] R, Z., J, M., & J, Y. (2013). Molecular mechanisms of the cartilage-specific microRNA-140 in osteoarthritis. Inflammation research : official journal of the European Histamine Research Society ... [et al.], 62(10). https://doi.org/10.1007/s00011-013-0654-8

[27] Z, L., Y, H., X, J., L, L., & H, G. (2022). PCB153 suppressed autophagy via PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling by the upregulation of microRNA-155 in rat primary chondrocytes. Toxicology and applied pharmacology, 449. https://doi.org/10.1016/j.taap.2022.116135

[28] Chen, Z., Jin, T., & Lu, Y. (2016). AntimiR-30b Inhibits TNF-α Mediated Apoptosis and Attenuated Cartilage Degradation through Enhancing Autophagy. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 40(5), 883–894. https://doi.org/10.1159/000453147

[29] S, Y., W, Z., Q, O., L, L., X, L., & Y, W. (2017). MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4. Stem cells international, 2017. https://doi.org/10.1155/2017/3028647

[30] Sassi, N., Laadhar, L., Allouche, M., Achek, A., Kallel-Sellami, M., Makni, S., & Sellami, S. (2014). WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology. Journal of Receptor and Signal Transduction Research, 34(2), 73–80. https: // doi. org/ 10. 3109/ 10799893. 2013.863919

[31] Zhang, M., Theleman, J. L., Lygrisse, K. A., & Wang, J. (2019). Epigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis. Gerontology, 65(4), 387–396. https: //doi. org/1 0. 1159/000496688

[32] Portal-Núñez, S., Esbrit, P., Alcaraz, M. J., & Largo, R. (2016). Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis. Biochemical Pharmacology, 108, 1–10. https://doi.org/10.1016/j.bcp.2015.12.012

[33] Jx, W., J, G., Sl, D., K, W., Jq, J., Y, W., … Pf, L. (2015). Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w. Molecular cell, 59(1). https://doi.org/10.1016/j.molcel.2015.05.003

[34] de Girolamo, L., Kon, E., Filardo, G., Marmotti, A. G., Soler, F., Peretti, G. M., … Chubinskaya, S. (2016). Regenerative approaches for the treatment of early OA. Knee surgery, sports traumatology, arthroscopy: official journal of the ESSKA, 24(6), 1826–1835. https://doi.org/10.1007/s00167-016-4125-y