Molecular mechanisms of taurine effect on the metabolism of blood cells and chondrocytes of knee articular cartilage in patients with late-stage rheumatoid arthritis

Previously, we demonstrated that the development of rheumatoid arthritis (RA) is accompanied not only by inflammation but also by disturbances in central metabolic processes, which are reflected in altered expression of genes involved in energy metabolism. Given the insufficient efficacy of current therapies and the occurrence of adverse events in some cases, the use of nutrients, such as taurine, may be reasonable.
Objective: to evaluate the effect of taurine on the expression of genes responsible for the main pathways of energy metabolism, as well as inflammatory and regenerative activity, during in vitro culture of blood cells and articular cartilage explants obtained from patients with late-stage RA.
Material and methods. Blood samples and articular cartilage explants were obtained from 20 patients with RA (3 men and 17 women; mean age 62.2±10.9 years; mean disease duration 18.2 years) prior to knee joint arthroplasty. Blood cells and cartilage explants were cultured in the presence of 50 μM taurine. Gene expression in cartilage explants was assessed using reverse transcription and real-time polymerase chain reaction.
Results and discussion. Cultivation of blood cells from patients with RA in the presence of 50 μM taurine resulted in a significant increase in the expression of genes encoding pyruvate kinase (PKM2), succinate dehydrogenase (SDHB), uncoupling protein 2 (UCP2), ATP synthase (ATP5B), and unc-51-like kinase 1 (ULK1). In cartilage explants, taurine also activated the expression of SDHB and UCP2 genes and, to a lesser extent, ULK1 (p=0.07). Moreover, cultivation of the studied tissues in the presence of taurine was associated with a marked decrease in the expression of tumor necrosis factor alpha (TNF-á). Culturing articular cartilage explants with taurine significantly increased the expression of the collagen type II gene (COL2A1).
Conclusion. Taurine exerts a beneficial effect on energy metabolism by increasing the expression of genes responsible for oxidative phosphorylation and autophagy in blood cells and articular cartilage explants, while reducing the expression of the inflammatory marker – TNF-á. However, unlike chondrocytes, taurine also enhanced glycolytic activity and increased ATP synthase expression in blood cells. Enhancement of the regenerative potential of chondrocytes in cartilage explants from patients with RA in the presence of taurine is evidenced by increased expression of the collagen type II gene.

1. Diaz-Gonzalez F, Hernandez-Hernandez MV. Rheumatoid arthritis. Med Clin (Barc). 2023 Dec 22;161(12):533-542. doi: 10.1016/j.medcli.2023.07.014.

2. Brown P, Pratt AG, Hyrich KL. Therapeutic advances in rheumatoid arthritis. BMJ. 2024 Jan 17:384:e070856. doi: 10.1136/bmj-2022-070856.

3. Xiang G, Gao M, Qin H, et al. Benefit-risk assessment of traditional Chinese medicine preparations of sinomenine using multicriteria decision analysis (mcda) for patients with rheumatoid arthritis. BMC Complement Med Ther. 2023 Feb 6;23(1):37. doi: 10.1186/s12906-023-03864-6.

4. Radu AF, Bungau SG. (2021). Management of rheumatoid arthritis: an overview. Cells. 2021 Oct 23;10(11):2857.doi: 10.3390/cells10112857.

5. Zhu X, Shen X, Hou X, Luo, et al. Total glucosides of paeony for the treatment of rheumatoid arthritis: a methodological and reporting quality evaluation of systematic reviews and meta-analyses. Int Immunopharmacol. 2020 Nov:88:106920. doi: 10.1016/j.intimp.2020.106920.

6. Weyand CM, Wu B, Goronzy JJ. The metabolic signature of T cells in rheumatoid arthritis. Curr Opin Rheumatol. 2020 Mar;32(2): 159-167. doi: 10.1097/BOR.0000000000000683.

7. Yang Z, Shen Y, Oishi H, et al. Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci Transl Med. 2016 Mar 23;8(331): 331ra38. doi: 10.1126/scitranslmed.aad7151.

8. Weyand CM, Zeisbrich M, Goronzy JJ. Metabolic signatures of T-cells and macrophages in rheumatoid arthritis. Curr Opin Immunol. 2017 Jun:46:112-120. doi: 10.1016/j.coi.2017.04.010.

9. Li Y, Liu Y, Wang C, et al. Succinate induces synovial angiogenesis in rheumatoid arthritis through metabolic remodeling and HIF-1 /VEGF axis. Free Radic Biol Med. 2018 Oct:126:1-14. doi: 10.1016/j.freeradbiomed.2018.07.009.

10. Wu B, Goronzy JJ, Weyand CM. Metabolic Fitness of T Cells in Autoimmune Disease. Immunometabolism. 2020;2(2):e200017. doi: 10.20900/immunometab20200017.

11. Chetina EV, Demidova NV, Markova GA. Metabolic aspects of clinical remission prediction from baseline blood gene expression in patients with rheumatoid arthritis treated with methotrexate. Modern Rheumatology Journal. 2019;13(2):47-54. (In Russ.). doi: 10.14412/1996-7012-2019-2-47-54

12. Li Y, Shen Y, Jin K, et al. The DNA Repair Nuclease MRE11A Functions as a Mito chondrial Protector and Prevents T Cell Pyroptosis and Tissue Inflammation. Cell Metab. 2019 Sep 3;30(3):477-492.e6. doi: 10.1016/j.cmet.2019.06.016.

13. Goodpaster BH, Sparks LM. Metabolic Flexibility in Health and Disease. Cell Metab. 2017 May 2;25(5):1027-1036. doi: 10.1016/j.cmet.2017.04.015.

14. Chetina EV, Demidova NV, Markova GA, et al. Predicting the effectiveness of methotrexate therapy based on basal expression of the AMP-activated protein kinase gene in the blood of patients with rheumatoid arthritis. Modern Rheumatology Journal. 2022;16(1):46-51. (In Russ.). doi: 10.14412/1996-7012-2022-1-46-51

15. Chetina EV, Satybaldyev AM, Markova GA, et al. Association between a low baseline level of gene expression of energy metabolism in the blood and the development of clinical remission in response to tofacitinib therapy in patients with rheumatoid arthritis. Modern Rheumatology Journal. 2021;15(3):20-6. (In Russ.). doi: 10.14412/1996-7012-2021-3-20-26

16. Min HK, Kim SH, Kim HR, et al. Therapeutic Utility and Adverse Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs in Inflammatory Arthritis. Int J Mol Sci. 2022 Nov 11;23(22):13913. doi: 10.3390/ijms232213913.

17. Wen C, Li F, Zhang L, et al. Taurine is Involved in Energy Metabolism in Muscles, Adipose Tissue, and the Liver. Mol Nutr Food Res. 2019 Jan;63(2):e1800536. doi: 10.1002/mnfr.201800536.

18. Singh P, Gollapalli K, Mangiola S, et al. Taurine deficiency as a driver of aging. Science. 2023 Jun 9;380(6649):eabn9257. doi: 10.1126/science.abn9257.

19. Ripps H, Shen W. Review: taurine: a “very essential” amino acid. Mol Vis. 2012:18: 2673-86.

20. Lambert IH, Kristensen DM, Holm JB, et al. Physiological role of taurine--from organism to organelle. Acta Physiol (Oxf). 2015 Jan;213(1):191-212. doi: 10.1111/apha.12365.

21. Ito T, Yoshikawa N, Inui T, et al. Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PLoS One. 2014 Sep 17;9(9):e107409. doi: 10.1371/journal.pone.0107409.

22. Chen C, Xia S, He J, et al. Roles of taurine in cognitive function of physiology, pathologies and toxication. Life Sci. 2019 Aug 15:231:116584. doi: 10.1016/j.lfs.2019.116584.

23. Imae M, Asano T, Murakami S. Potential role of taurine in the prevention of diabetes and metabolic syndrome. Amino Acids. 2014 Jan;46(1):81-8. doi: 10.1007/s00726-012-1434-4.

24. Pasantes-Morales H, Hernandez-Benitez R. Taurine and brain development: trophic or cytoprotective actions? Neurochem Res. 2010 Dec;35(12):1939-43. doi: 10.1007/s11064-010-0262-8.

25. Jamshidzadeh A, Heidari R, Abasvali M, et al. Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia. Biomed Pharmacother. 2017 Feb:86:514-520. doi: 10.1016/j.biopha.2016.11.095.

26. Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012 Jun;42(6):2223-32. doi: 10.1007/s00726-011-0962-7.

27. Wenz T, Rossi SG, Rotundo RL, et al. Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20405-10. doi: 10.1073/pnas.0911570106.

28. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018 Sep;15(9):505-522. doi: 10.1038/s41569-018-0064-2.

29. Tchetina EV, Antoniou J, Tanzer M, et al. TGFbeta2 suppresses collagen cleavage in cultured human osteoarthritic cartilage, reduces expression of genes associated with chondrocyte hypertrophy and degradation, and increases prostaglandin E2 production. Am J Pathol. 2006 Jan;168(1):131-40. doi: 10.2353/ajpath.2006.050369.

30. Tchetina EV, Di Battista JA, Zukor DL, et al. Prostaglandin E2 suppresses collagen cleavage in cultured human osteoarthritic cartilage, involves a reduction in expression of proinflammatory cytokines and those associated with chondrocyte hypertrophy. Arthritis Res Ther. 2007;9(4):R75. doi: 10.1186/ar2273.

31. Jahid M, Khan KU, Rehan-Ul-Haq, et al. Overview of Rheumatoid Arthritis and Scientific Understanding of the Disease. Mediterr J Rheumatol. 2023 Aug 1;34(3):284-291. doi: 10.31138/mjr.20230801.oo.

32. Perez-Hernandez E, Pastrana-Carballo JJ, Gomez-Chavez F, et al. A Key Metabolic Regulator of Bone and Cartilage Health. Endocrinol Metab (Seoul). 2022 Aug;37(4):559-574. doi: 10.3803/EnM.2022.1443.

33. Sharma S, Agnihotri N, Kumar S. Targeting fuel pocket of cancer cell metabolism: A focus on glutaminolysis. Biochem Pharmacol. 2022 Apr:198:114943. doi: 10.1016/j.bcp.2022.114943.

34. Shimada-Takaura K, Takahashi K, Ito T, Schaffer S. Role for Taurine in Development of Oxidative Metabolism After Birth. Adv Exp Med Biol. 2017:975 Pt 2:1047-1057. doi: 10.1007/978-94-024-1079-2_83.

35. Maguire D, Shah J, McCabe M. Assaying ATP synthase rotor activity. Adv Exp Med Biol. 2006:578:67-72. doi: 10.1007/0-387-29540-2_11.

36. Schaffer SW, Shimada-Takaura K, Jong CJ, et al. Impaired energy metabolism of the taurine-deficient heart. Amino Acids. 2016 Feb;48(2):549-58. doi: 10.1007/s00726-015-2110-2.

37. Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012 Jun;42(6):2223-32. doi: 10.1007/s00726-011-0962-7. Epub 2011 Jun 21.

38. Bettedi L, Foukas LC. Growth factor, energy and nutrient sensing signalling pathways in metabolic ageing. Biogerontology. 2017 Dec; 18(6):913-929. doi: 10.1007/s10522-017-9724-6.

39. Sevin G, Ozsar G. Taurine inhibits increased MMP-2 expression in a model of oxidative stress induced by glutathione depletion in rabbit heart. Eur J Pharmacol. 2013 Apr 15; 706(1-3):98-106. doi: 10.1016/j.ejphar.2013.02.052.

40. Marcinkiewicz J, Kontny E. Taurine and inflammatory diseases. Amino Acids. 2014 Jan; 46(1):7-20. doi: 10.1007/s00726-012-1361-4.

41. Yin Y, Guo M, Lipsky PE, Zhang X. Can we cure rheumatoid arthritis? Curr Opin Immunol. 2025 Jun:94:102561. doi: 10.1016/j.coi.2025.102561.

42. Rondanelli M, Perdoni F, Peroni G, et al. Ideal food pyramid for patients with rheumatoid arthritis: A narrative review. Clin Nutr. 2021 Mar;40(3):661-689. doi: 10.1016/j.clnu.2020.08.020. Epub 2020 Sep 2.