Research Article
American Journal of BioMedicine
Volume 12, Issue 1, 2024, Pages 11-20 10.18081/2333-5106/2024.12/11
M Sharma1 , H Mishra, S Singh ,K Longkumer, M Dhuria *
Received 30 August 2023; revised 29 October 2023; accepted 11 December 2023; published 24 March 2024
Abstract
Osteoarthritis is the most common chronic degenerative disease worldwide; it mainly affects elderly people. This disease can involve nearly any joint in the human body, and the most common symptoms include joint pain and disordered articular functions. Inflammasomes (NLRP3) which are induced by nuclear factor kappa B (NF-κB) signaling and can convert interleukin-1β (IL-1β) and IL-18 into mature proinflammatory cytokines are considered a factor in low-grade inflammatory pathology. This study aimed to explore the mechanisms underlying CDKN1A-in osteoarthritis. Chondrocytes were collected and isolated from 22 patients with osteoarthritis (average age 50.22 ± 2.15) and healthy volunteers (average age 51.12 ± 2.34) were enrolled as the control group from June 2021 to June 2023. mRNA expression levels of CDKN1A, NLRP3, and cleaved-Caspase1) were detected by real-time PCR. Cell activity was calculated with CCK-8. It has been found that CDKN1A regulates DNA damage repair, which contributes to the improvement of osteoarthritis by regulating the pyroptosis of cartilage cells. However, the exact mechanistic effects are still unknown.
Keywords: Osteoarthritis; CDKN1A; Cohort Study; Inflammasomes
Copyright © 2024 Dhuria, et al. This article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cited by CrossRef (1)
Cited by Scopus (0)
1. Bortoluzzi A, Furini F, Scirè CA. Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors. Autoimmun Rev. 2018;17(11):1097-1104. https://doi.org/10.1016/j.autrev.2018.06.002 |
|||
2. Hwang HS, Kim HA. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis. Int J Mol Sci. 2015;16:26035-26054. https://doi.org/10.3390/ijms161125943 |
|||
3. Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 2016;4:15040. https://doi.org/10.1038/boneres.2015.40 |
|||
4. McAllister MJ, Chemaly M, Eakin AJ, Gibson DS, McGilligan VE. NLRP3 as a potentially novel biomarker for the management of osteoarthritis. Osteoarthritis Cartilage. 2018; 26:612-619. https://doi.org/10.1016/j.joca.2018.02.901 |
|||
5. Zhu S, Zhu J, Zhen G, et al. Subchondral bone osteoclasts induce sensory innervation and osteoarthritis pain. J Clin Invest. 2019;129:1076-1093. https://doi.org/10.1172/JCI121561 |
|||
6. Gao YL, Zhai JH, Chai YF. Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis. Mediators Inflamm. 2018; 2018:5823823. https://doi.org/10.1155/2018/5823823 |
|||
7. Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140:821-832. https://doi.org/10.1016/j.cell.2010.01.040 |
|||
8. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10:417-426. https://doi.org/10.1016/S1097-2765(02)00599-3 |
|||
9. Samways DS, Li Z, Egan TM. Principles and properties of ion flow in P2X receptors. Front Cell Neurosci. 2014;8:6. https://doi.org/10.3389/fncel.2014.00006 |
|||
10. Liu X, Zhang X, Ding Y, et al. Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming. Antioxid Redox Signal. 2017; 26:28-43. https://doi.org/10.1089/ars.2015.6615 |
|||
11. Mathews RJ, Robinson JI, Battellino M, et al. Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment. Ann Rheum Dis. 2014;73:1202-1210. https://doi.org/10.1136/annrheumdis-2013-203276 |
|||
12. Wang X, Hunter D, Xu J, Ding C. Metabolic triggered inflammation in osteoarthritis. Osteoarthritis Cartilage. 2015;23:22-30. https://doi.org/10.1016/j.joca.2014.10.002 |
|||
13. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 2015;21:677-687. https://doi.org/10.1038/nm.3893 |
|||
14. Pandey A, Shen C, Feng S, Man SM. Cell biology of inflammasome activation. Trends Cell Biol. 2021;31:924-939. https://doi.org/10.1016/j.tcb.2021.06.010 |
|||
15. Oliveria SA, Felson DT, Reed JI, Cirillo PA, Walker AM. Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis Rheum. 1995;38:1134-1141. https://doi.org/10.1002/art.1780380817 |
|||
16. Hochheiser IV, Pilsl M, Hagelueken G, et al. Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature. 2022;604:184-189. https://doi.org/10.1038/s41586-022-04467-w |
|||
17. Strowig T, Henao-Mejia J, Elinav E, Flavell R. Inflammasomes in health and disease. Nature. 2012;481:278-286. https://doi.org/10.1038/nature10759 |
|||
18. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 2010;11:136-140. https://doi.org/10.1038/ni.1831 |
|||
19. Huang P, Ouyang DJ, Chang S, et al. Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells. Cell Commun. Signal. 2018;16:92. https://doi.org/10.1186/s12964-018-0304-4 |
|||
20. Wiese C, Rudolph JH, Jakob B, et al. PCNA-dependent accumulation of CDKN1A into nuclear foci after ionizing irradiation. DNA Repair. 2012;11:511-521. https://doi.org/10.1016/j.dnarep.2012.02.006 |
|||
21. Georgakilas AG, Martin OA, Bonner WM. p21. a two-faced genome guardian. Trends Mol. Med. 2017;23:310-319. https://doi.org/10.1016/j.molmed.2017.02.001 |
|||
22. Han C, Liu Z, Zhang Y, et al. Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling. Nat. Immunol. 2020;21:546-554. https://doi.org/10.1038/s41590-020-0641-5 |
|||
23. Roos W, Thomas A, Kaina B. DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer. 2016;16:20-33. https://doi.org/10.1038/nrc.2015.2 |
|||
24. Aigner T, Hemmel M, Neureiter D, et al. Apoptotic cell death is not a widespread phe-nomenonin normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apop-tosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum. 2001;44:1304-1312. https://doi.org/10.1002/1529-0131(200106)44:6<1304::AID-ART222>3.0.CO;2-T |
|||
25. Jung YS, Qian Y, Chen X. Examination of the expanding pathways for the regulation of p21expression and activity. Cell Signal. 2010;22:1003-1112. https://doi.org/10.1016/j.cellsig.2010.01.013 |
|||
26. Charlier E, Deroyer C, Ciregia F, et al. Chondrocyte dedifferentiation and osteoar-thritis (OA). Biochem Pharmacol. 2019;165:49-65. https://doi.org/10.1016/j.bcp.2019.02.036 |
|||
27. Ovacs SB, Miao EA. Gasdermins: Effec-tors of Pyroptosis. Trends Cell Biol. 2017;27: 673-684. https://doi.org/10.1016/j.tcb.2017.05.005 |
|||
28. Hoemann CD, Tran-Khanh N, Chevrier A, et al. Chondroinduction Is the Main Carti-lage Repair Response to Microfracture and Microfracture With BST-CarGel: Results as Shown by ICRS-II Histological Scoring and a Novel Zonal Collagen Type Scoring Method of Human Clinical Biopsy Specimens. Am J Sports Med. 2015;43:2469-2480. https://doi.org/10.1177/0363546515593943 |
|||
29. Nasi S, Ea HK, So A, Busso N. Revisiting the Role of Interleukin-1 Pathway in Osteoarthritis: Interleukin-1alpha and -1beta, and NLRP3 Inflammasome Are Not Involved in the Pathological Features of the Murine Menisectomy Model of Osteoarthritis. Front Pharmacol. 2017;8:282. https://doi.org/10.3389/fphar.2017.00282 |
|||
30. Denoble AE, Huffman KM, Stabler TV, et al. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Natl Acad Sci U S A. 2019;108:2088-2093. https://doi.org/10.1073/pnas.1012743108 |
|||
31. Bougault C, Gosset M, Houard X, et al. Stress-induced cartilage degradation does not depend on the NLRP3 inflammasome in human osteoarthritis and mouse models. Arthritis Rheum.2012;64:3972-3981. https://doi.org/10.1002/art.34678 |
|||
32. Borgonio Cuadra VM, Gonzalez-Huerta NC, Romero-Cordoba S, Hidalgo-Miranda A, Miranda-Duarte A. Altered expression of circulating microRNA in plasma of patients with primary osteoarthritis and in silico analysis of their pathways. PLoS One.2014;9:e97690. https://doi.org/10.1371/journal.pone.0097690 |
|||
33. Helmick CG, Felson DT, Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum.2008;58:15-25. https://doi.org/10.1002/art.23177 |
How to cite
Sharma M, Mishra H, Singh S, Longkumer K, Dhuria M. CDKN1A down-regulation of inflammasomes and pro-inflammatory cytokines in pyroptosis of cartilage cells. American Journal of BioMedicine 2024; 12(1):11-20.
More Citation
Article Metrics
Permissions
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in American Journal of BioMedicine are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.