ROLE OF THE NITROGEN OXIDE SYSTEM AND PRO-INFLAMMATORY CYTOKINES IN THE PATHOGENETIC MECHANISMS OF DEGENERATIVE JOINT DISEASES
Abstract and keywords
Abstract (English):
It was investigated the levels of nitric oxide, pro-inflammatory cytokines (IL-1β, IL-6, IL-18, TNFα), leptin and uric acid in blood plasma and synovial fluid (SF) as biomarkers of post-traumatic gonarthrosis (PTGA), as well as their association with radiological stage of PTGA. It was found that in patients with early and late stages of post-traumatic arthrosis of the knee joint, the level of circulating pro-inflammatory mediators: nitrites / nitrates (NOx), IL-6, and uric acid was increased compared with healthy individuals. Circulating levels of NOx, IL-1, IL-6, uric acid, leptin, and a combination of IL-6 and leptin can be potential diagnostic tests according to the ROC curve analysis. Plasma levels of NOx, IL-6, IL-18, and leptin significantly correlated with their levels in the SF. The severity of PTGA correlated with the level of leptin in plasma and SF, as well as with the level of synovial IL-18. The association of polymorphic variants of the nNOS and eNOS genes with the risk of developing post-traumatic gonarthrosis (PTGA) in residents of the Rostov region was studied. It has been established that the -84A allele of the nNOS polymorphic gene is associated with the risk of developing PTGA.

Keywords:
post-traumatic gonarthrosis, blood plasma, synovial fluid, nitric oxide, pro-inflammatory cytokines, leptin, NO synthase genes
Text
Publication text (PDF): Read Download
References

1. Loeser R.F., Steven R.G., Carla R.S., Goldring M.B. Osteoarthritis: A Disease of the Joint as an Organ. Arthritis Rheum., 2012, vol. 64, no. 6. DOI:https://doi.org/10.1002/art.34453.

2. Saito T., Tanaka S. Molecular mechanisms underlying osteoarthritis development: Notch and NF-κB. Arthritis Res. Ther, 2017, vol. 19, no. 94. DOI:https://doi.org/10.1186/s13075-017-1296-y.

3. Karateev A.E., Lila A.M. Osteoartrit: sovremennaya klinicheskaya koncepciya i nekotorye perspektivnye terapevticheskie podhody. Nauchno-praktich. revmatol, 2018, t. 56, № 1. DOI: org/10.14412/1995-4484-2018-70-81. @@Karateev A.E., Lila A.M. Osteoartrit: sovremennaya klinicheskaya koncepciya i nekotorye perspektivnye terapevticheskie podhody. Nauchno-praktich. revmatol, 2018, vol. 56, no. 1. DOI: org/10.14412/1995-4484-2018-70-81. (In Russ.)

4. Vnukov V.V., Panina S.B., Krolevets I.V., Milutina N.P., Ananyan A.A., Zabrodin M.A., Plotnikov A.A. Specificities of Oxidative Stress in the Blood and Synovial Fluid in Knee Osteoarthritis. Advances in Gerontology, 2015, vol. 5, no. 4. DOI:https://doi.org/10.1134/S2079057015040220.

5. Abramson S.B. Nitric oxide in inflammation and pain associated with osteoarthritis. Arthritis Res. Ther., 2008, vol. 10, no. S2. DOI:https://doi.org/10.1186/ar2463.

6. Mabey T., Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. J. Am. Acad. Orthop. Surg., 2015, vol. 6, no. 1. DOI:https://doi.org/10.5312/wjo.v6.i1.95.

7. Olson S.A., Horne P., Furman B., Huebner J., Al-Rashid M., Kraus V.B., Guilak F. The role of cytokines in posttraumatic arthritis. Am. Acad. Orthop. Surg., 2014, vol. 22, no. 1. DOI:https://doi.org/10.5435/JAAOS-22-01-29.

8. Vnukov V.V., Krolevets I.V., Panina S.B., Milyutina N.P., Ananyan A.A., Plotnikov A.A., Zabrodin M.A. The Association Between NO-Synthase Gene Polymorphisms and the Development of Post-Traumatic Knee Osteoarthritis Among Residents of Rostov Region.Russian J. Genetics: Applied Research, 2017, vol. 7, no. 2. DOI:https://doi.org/10.1134/S2079059717020150.

9. Anderson D.D., Chubinskaya S., Guilak F., Martin J.A., Oegema T.R., Olson S.A., Buckwalter J.A. Post-Traumatic Osteoarthritis: Improved Understanding and Opportunities for Early Intervention. J. Orthop. Res., 2011, vol. 29, no 6. DOI:https://doi.org/10.1002/jor.21359.

10. Valdes A.M., Spector T.D. The contribution of genes to osteoarthritis. Rheum. Dis. Clin. North. Am., 2008, vol. 34, no. 3, doi.org/10.1016/j.rdc.2008.04.008.

11. Valdes A.M., Doherty S.A., Muir K.R., Wheeler M., Maciewicz R.A., Zhang W., Dohert M. The genetic contribution to severe post-traumatic osteoarthritis. Ann. Rheum. Dis., 2013, vol. 72, no. 10. DOI:https://doi.org/10.1136/annrheumdis-2012-202562.

12. Golikov P.P., Nikolaeva N.Yu. Metod opredeleniya nitrita/nitrata (NOx-) v syvorotke krovi. Biomed. himiya, 2004, t. 50, № 1. @@Golikov P.P., Nikolaeva N.Yu. Metod opredeleniya nitrita/nitrata (NOx-) v syvorotke krovi. Biomed. himiya, 2004, vol. 50, no. 1. (In Russ.)

13. Simundic A.-M. Diagnostic Accuracy. Part 1: Basic Concepts: Sensitivity and Specificity, ROC Analysis, STARD Statement. Point of Care, 2012, vol. 11, no 1.

14. Furman B.D., Mangiapani D.S., Zeitler E., Bailey K.N., Horne P.H., Huebner J.L., Kraus V.B., Guilak F., Olson S.A. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis. Arthritis Research & Therapy, 2014, vol. 16, no. 3. DOI:https://doi.org/10.1186/ar4591.

15. Bigoni M., Sacerdote P., Turati M., Franchi S., Gandolla M., Gaddi D., Moretti S., Munegato D., Augusti C.A., Bresciani E., Omeljaniuk R.J., Locatelli V., Torsello A. Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury. J. Orthop. Res., 2013, vol. 31, no. 2. DOI:https://doi.org/10.1002/jor.22208.

16. Teunis T., Beekhuizen M., van Osch G.V.M., Schuurman A.H., Creemers L.B., van Minnen L.P. Soluble mediators in posttraumatic wrist and primary knee osteoarthritis. Arch. Bone. Jt. Surg., 2014, vol. 2, no. 3. DOI: abjs.mums.ac.ir.

17. Ning L., Ishijima M., Kaneko H., Kurihara H., Arikawa-Hirasawa E., Kubota M., Liu L., Xu Z., Futami I., Yusup A., Miyahara K., Xu S., Kaneko K., Kurosawa H. Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis.Int. Orthop., 2011, vol. 35, no. 6. DOI:https://doi.org/10.1007/s00264-010-1045-1.

18. de Albornoz P.M., Forriol F. Changes in synovial fluid in different knee-joint diseases. Rev. Esp. Cir. Ortop. Traumatol., 2012, vol. 56, no. 2. DOI:https://doi.org/10.1016/j.recote.2012.03.003.

19. Ku J.H., Lee C.K., Joo B.S., An B.M., Choi S.H., Wang T.H., Cho H.L. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis. Clin. Rheumatol., 2009, vol. 28, no. 8. DOI: org/10.1007/s10067-009-1242-8.

20. Cao R., Brakenhielm E., Wahlestedt C., Thyberg J., Cao Y. (2001) Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc. Natl. Acad. Sci. USA, 2001, vol. 98, no. 11. DOI:https://doi.org/10.1073/pnas.101564798.

21. Denoble A.E., Huffman K.M., Stabler T.V., Kelly S.J., Hershfield M.S., McDaniel G.E., Coleman R.E., Kraus V.B. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc. Natl. Acad. Sci. USA, 2011, vol. 108, no. 5. DOI:https://doi.org/10.1073/pnas.1012743108.

22. Jitprasertwong P., Jaedicke K.M., Nile C.J., Preshaw P.M., Taylor J.J. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine, 2014, vol. 65, no. 2. DOI:https://doi.org/10.1016/j.cyto.2013.10.008.

23. Vecchione C., Maffei A., Colella S., Aretini A., Poulet R., Frati G., Gentile M.T., Fratta L., Trimarco V., Trimarco B., Lembo G. Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes, 2002, vol. 51, no. 1. DOI:https://doi.org/10.2337/diabetes.51.1.168.

24. Joffin N., Niang F., Forest C., Jaubert A.-M. Is there NO help for leptin? Biochimie, 2012, vol. 94, no. 10. DOI:https://doi.org/10.1016/j.biochi.2012.06.017.

25. Abramson S.B. Osteoarthritis and nitric oxide. Osteoarthritis Cartilage, 2008, vol. 16, no. S2. DOI:https://doi.org/10.1016/S1063-4584(08)60008-4.

26. Feelisch M. The chemical biology of nitric oxide - an outsider’s reflections about its role in osteoarthritis. Osteoarthritis Cartilage, 2008, vol. 16, no. 2. DOI:https://doi.org/10.1016/S1063-4584(08)60007-2.

27. Castro R.R., Cunha F.Q., Silva F.S.Jr., Rocha F.A. A quantitative approach to measure joint pain in experimental osteoarthritis-evidence of a role for nitric oxide. Osteoarthritis Cartilage, 2006, vol. 14, no. 8. DOI:https://doi.org/10.1016/j.joca.2006.01.013.

28. Pautz A., Art J., Hahn S., Nowag S., Voss C., Kleinert H. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide, 2010, vol. 23, no. 2. DOI:https://doi.org/10.1016/j.niox.2010.04.007.

29. Loeser R.F., Carlson C.S., Del Carlo M., Cole A. Detection of nitrotyrosine in aging and osteoarthritic cartilage: Correlation of oxidative damage with the presence of interleukin-1beta and with chondrocyte resistance to insulin-like growth factor 1. Arthritis Rheum., 2002, vol. 46, no. 9. DOI:https://doi.org/10.1002/art.10496.

30. Yan Q., Feng Q., Beier F. Endothelial nitric oxide synthase deficiency in mice results in reduced chondrocyte proliferation and endochondral bone growth. Arthritis Rheum., 2010, vol. 62, no. 7. DOI:https://doi.org/10.1002/art.27486.

31. Yan Q., Feng Q., Beier F. Reduced chondrocyte proliferation, earlier cell cycle exit and increased apoptosis in neuronal nitric oxide synthase-deficient mice. Osteoarthritis Cartilage, 2012, vol. 20, no. 2. DOI:https://doi.org/10.1016/j.joca. 2011.11.014.

32. Miao X., Garcia-Barcelo M.M., So M., Tang W., Dong X., Wang B., Mao J., Ngan E.S., Chen Y., Lui V.C., Wong K.K., Liu L., Tam P.K. Lack of association between nNOS -84G > A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population. J. Pediatr. Surg., 2010, vol. 45, no. 4. DOI:https://doi.org/10.1016/j.jpedsurg. 2009.07.067.

33. Olson S.Y., Garban H.J. Regulation of apoptosis-related genes by nitric oxide in cancer. Nitric Oxide, 2008, vol. 19, no. 2. DOI:https://doi.org/10.1016/j.niox.2008.04.005.

34. Nakayama M., Yasue H., Yoshimura M., Shimasaki Y., Kugiyama K., Ogawa H., Motoyama T., Saito Y., Ogawa Y., Miyamoto Y., Nakao K. T-786 C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation, 1999, vol. 99, no. 22. DOI:https://doi.org/10.1161/01.cir.99.22.2864.

35. Asif A.R., Oellerich M., Armstrong V.W., Hecker M., Cattaruzza M. T-786C polymorphism of the nos-3 gene and the endothelial cell response to fluid shear stress - a proteome analyses. J. Proteome. Res., 2009, vol. 8, no. 6. DOI:https://doi.org/10.1021/pr800998k.


Login or Create
* Forgot password?