Modern possibilities of pathogenetic therapy of osteoarthritis at the molecular-cellular level
Belyaeva I.B., Mazurov V.I.
North-West State Medical University named after I.I. Mechnikov, St. Petersburg
Osteoarthritis (OA) is the most common joint disease, which is one of the main causes of disability. Significant progress has been made recently in studying the pathogenesis of OA, but many questions remain unsolved. In the progression of OA a significant role is played by an increase in the production of pro-inflammatory cytokines, which induce the expression of matrix metalloproteinases (MMPs) and eicosanoids, which can cause articular cartilage damage and the proliferation of synovial cells. The review presents the results of in vitro studies of the effect of Alflutop on certain pathogenetic links of OA using as an experimental model the CHON-001 cells (human bone cartilage chondrocytes) and the cells of a rabbit cartilage. The genetic, cellular and molecular mechanisms of the Alflutop action stimulate the proliferation of chondrocytes, activate the synthesis of extracellular matrix by modulating the transforming growth factor-β, inhibiting hyaluronidase, oxidative stress, and extracellular expression of the genes of pro-inflammatory cytokines (interleukin (IL) 6, IL8 and IL1b) (in vitro), which determines both the symptom-modifying and the structural-modifying effect of the drug in OA.
Key words: osteoarthritis, chondrocyte regeneration, articular cartilage, pro-inflammatory cytokines, Alflutoр.
For citation: Belyaeva I.B., Mazurov V.I. Modern possibilities of pathogenetic therapy of osteoarthritis at the molecular-cellular level // RMJ. MEDICAL REVIEW. 2017. № 1. P. 26–30.
References
1. Мазуров В.И., Трофимова А.С., Трофимов Е.А. Факторы риска и некоторые аспекты патогенеза остеоартрита // Вестник СЗГМУ им. И.И. Мечникова. 2016. № 2. С. 116–125 [Mazurov V.I., Trofimova A.S., Trofimov E.A. Faktory riska i nekotorye aspekty patogeneza osteoartrita // Vestnik SZGMU im. I.I. Mechnikova. 2016. № 2. S. 116–125 (in Russian)].
2. Лила А.М. Остеоартрит. Ревматология. Фармакотерапия без ошибок: руководство для врачей / под ред. В.И. Мазурова. М.: Е-ното, 2017. С. 351–379 [Lila A.M. Osteoartrit. Revmatologija. Farmakoterapija bez oshibok: rukovodstvo dlja vrachej / pod red. V.I. Mazurova. М.: E-noto, 2017. S. 351–379 (in Russian)].
3. Самойлов В.В., Мироманов А.М., Самойлова С.И. Значение цитокинов в патогенезе остеоартроза // Забайкальский медицинский вестник. 2014. № 2. С. 119–125 [Samojlov V.V., Miromanov А.М., Samojlov S.I. Znachenie citokinov v patogeneze osteoartroza // Zabajkal'skij medicinskij vestnik. 2014. № 2. S. 119–125 (in Russian)].
4. Felson D.T., Lawrence R.C., Dieppe P.A. et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors // Ann Intern Med. 2000. Vol. 133. P. 635–646.
5. Lane S.R., Trindade M.C., Ikenoue T. et al. Effects of shear stress on articular chondrocyte metabolism // Biorheology. 2000. Vol. 37(1-2). P. 95–107.
6. Sandell L.J., Aigner T. Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis // Arthritis Research and Therapy. 2001. Vol. 3. P. 107.
7. Tallheden T., Bengtsson C., Brantsing C. et al. Proliferation and differentiation potential of chondrocytes from osteoarthritic patients // Arthritis Research and Therapy. 2005. Vol. 7. P. R560.
8. Bruyere О., Cooper С., Pelletier J.P. et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis – From evidence-based medicine to the real-life setting // Semin Arthritis Rheum. 2016. Vol. 45(4 Suppl). P. 3–11.
9. Goldring M.B., Otero M., Plumb D.A. et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism // European Cells and Materials. 2011. Vol. 21. P. 202–220.
10. Bellucci F., Meini S., Cucchi P. et al. Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis // Osteoarthritis and Cartilage. 2013. Vol. 21. P. 1774–1780.
11. Schuerwegh A.J., Dombrecht E.J., Stevens W.J. et al. Influence of pro-inflammatory (IL-lα, IL-6, TNF-α, IFN-y) and anti-inflammatory (IL-4) cytokines on chondrocyte function // OsteoArthritis and Cartilage, Biomechanics and Cartilage Inflammation. 2003. Vol. 11. P. 681–687.
12. Craciun M.L., Vacaru A.M., Ene M.D. et al. pH influence on different bovine testicular hyaluronidase determination assays // Academy of Romanian Scientists, Annals Series on Biological Science .2016. Vol. 5(1).
13. Stem R., Asari A.A., Sugahara K.N. Hyaluronan fragments: an information-rich system // Eur J Cell Bio. 2006. Vol. 85(8). P. 699–715.
14. Juranek I., Stem R., Soltes L. Hyaluronan peroxidation is required for normal synovial function; An hypothesis // Medical Hypotheses. 2014. Vol. 82. P. 662–666.
15. Rosoiu N., Lascarache Gh. A natural extraction drug used for the treatment of degenerative diseases // Rev.Roum.Biochim. Ed. Academiei Romane. 1994. Vol. 31. P. 57–63.
16. Rosoiu N., Nita R., Ene M.D. et al. Certain bioactive effects of complexes rich in glycosaminoglycans obtained from small sea fish // Roumanian Biotechnological Lette. 2010. Vol. 15 (5). P. 5566–5575.
17. Li D., Wang W. Reactive Oxygen Species; The 2-Edged Sword of Osteoarthritis // Am JMed Sci. 2012. Vol. (Issue 6). P. 486–490.
18. Guilak F., Fermor B., Keefe F.J. et al. The Role of Biomechanics and Inflammation in Cartilage Injury and Repair // Clinical Orthopaedics and Related Research Number. 2004. Vol. 423. P. 17–26.
19. Onyekwelu I., Goldring M.B., Hidaka C. Chondrogenesis, joint formation, and articular cartilage regeneration // J Cell Biochem. 2009. Vol. 107(3). P. 383–392.
20. Lefebvre V., Smits P. Transcriptional control of chondrocyte fate and differentiation // Birth Defects Res C Embryo Today. 2005. Vol. 75(3). P. 200–212.
21. Olariu l., Dumitriu B., Manuela Ene D. et al. Alflutop® Modulates “In Vitro” Relevant Mechanisms Of Osteoarthritic Pathology // Academy of Romanian Scientists Annals Series on Biological Sciences. 2017. Vol. 6. P. 82–99.
22. Musumeci G., Aiello F.C., Szychlinska M.A. et al. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression // Int. J. Mol. Sci. 2015. Vol.16. P. 6093–6112.
23. Aebi H.E. Catalase in Bergmeyer, HU, Methods in enzymatic analysis // Weinheim: Verlag Chemie. 1978. P. 273–286.
24. Olariu L., Pyatigorskaya N., Dumitriu B. et al. In vitro chondro-restitutive capacity of Alflutop® proved on chondrocytes cultures // Romanian Biotechnological Letters. 2016. Vol. 22(6). P. 12047–12053.
25. Olariu L., Dumitriu B., Buse E., Rosoiu N. The in vitro” effect of Alflutop product on some extracellular signaling factors involved in the osteoarthicular pathology inflammation // Analele AOSR. 2015. Vol. 4 (2). P. 7–18.
26. Olariu L., Vacaru A., Pyatigorskaya N. et al. Original romanian product involved in cellular chondro -modulatory mechanisms. Euroinvent medalia de aur // Catalog Euroinvent. 2016. P. 437.
2. Лила А.М. Остеоартрит. Ревматология. Фармакотерапия без ошибок: руководство для врачей / под ред. В.И. Мазурова. М.: Е-ното, 2017. С. 351–379 [Lila A.M. Osteoartrit. Revmatologija. Farmakoterapija bez oshibok: rukovodstvo dlja vrachej / pod red. V.I. Mazurova. М.: E-noto, 2017. S. 351–379 (in Russian)].
3. Самойлов В.В., Мироманов А.М., Самойлова С.И. Значение цитокинов в патогенезе остеоартроза // Забайкальский медицинский вестник. 2014. № 2. С. 119–125 [Samojlov V.V., Miromanov А.М., Samojlov S.I. Znachenie citokinov v patogeneze osteoartroza // Zabajkal'skij medicinskij vestnik. 2014. № 2. S. 119–125 (in Russian)].
4. Felson D.T., Lawrence R.C., Dieppe P.A. et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors // Ann Intern Med. 2000. Vol. 133. P. 635–646.
5. Lane S.R., Trindade M.C., Ikenoue T. et al. Effects of shear stress on articular chondrocyte metabolism // Biorheology. 2000. Vol. 37(1-2). P. 95–107.
6. Sandell L.J., Aigner T. Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis // Arthritis Research and Therapy. 2001. Vol. 3. P. 107.
7. Tallheden T., Bengtsson C., Brantsing C. et al. Proliferation and differentiation potential of chondrocytes from osteoarthritic patients // Arthritis Research and Therapy. 2005. Vol. 7. P. R560.
8. Bruyere О., Cooper С., Pelletier J.P. et al. A consensus statement on the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis – From evidence-based medicine to the real-life setting // Semin Arthritis Rheum. 2016. Vol. 45(4 Suppl). P. 3–11.
9. Goldring M.B., Otero M., Plumb D.A. et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism // European Cells and Materials. 2011. Vol. 21. P. 202–220.
10. Bellucci F., Meini S., Cucchi P. et al. Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis // Osteoarthritis and Cartilage. 2013. Vol. 21. P. 1774–1780.
11. Schuerwegh A.J., Dombrecht E.J., Stevens W.J. et al. Influence of pro-inflammatory (IL-lα, IL-6, TNF-α, IFN-y) and anti-inflammatory (IL-4) cytokines on chondrocyte function // OsteoArthritis and Cartilage, Biomechanics and Cartilage Inflammation. 2003. Vol. 11. P. 681–687.
12. Craciun M.L., Vacaru A.M., Ene M.D. et al. pH influence on different bovine testicular hyaluronidase determination assays // Academy of Romanian Scientists, Annals Series on Biological Science .2016. Vol. 5(1).
13. Stem R., Asari A.A., Sugahara K.N. Hyaluronan fragments: an information-rich system // Eur J Cell Bio. 2006. Vol. 85(8). P. 699–715.
14. Juranek I., Stem R., Soltes L. Hyaluronan peroxidation is required for normal synovial function; An hypothesis // Medical Hypotheses. 2014. Vol. 82. P. 662–666.
15. Rosoiu N., Lascarache Gh. A natural extraction drug used for the treatment of degenerative diseases // Rev.Roum.Biochim. Ed. Academiei Romane. 1994. Vol. 31. P. 57–63.
16. Rosoiu N., Nita R., Ene M.D. et al. Certain bioactive effects of complexes rich in glycosaminoglycans obtained from small sea fish // Roumanian Biotechnological Lette. 2010. Vol. 15 (5). P. 5566–5575.
17. Li D., Wang W. Reactive Oxygen Species; The 2-Edged Sword of Osteoarthritis // Am JMed Sci. 2012. Vol. (Issue 6). P. 486–490.
18. Guilak F., Fermor B., Keefe F.J. et al. The Role of Biomechanics and Inflammation in Cartilage Injury and Repair // Clinical Orthopaedics and Related Research Number. 2004. Vol. 423. P. 17–26.
19. Onyekwelu I., Goldring M.B., Hidaka C. Chondrogenesis, joint formation, and articular cartilage regeneration // J Cell Biochem. 2009. Vol. 107(3). P. 383–392.
20. Lefebvre V., Smits P. Transcriptional control of chondrocyte fate and differentiation // Birth Defects Res C Embryo Today. 2005. Vol. 75(3). P. 200–212.
21. Olariu l., Dumitriu B., Manuela Ene D. et al. Alflutop® Modulates “In Vitro” Relevant Mechanisms Of Osteoarthritic Pathology // Academy of Romanian Scientists Annals Series on Biological Sciences. 2017. Vol. 6. P. 82–99.
22. Musumeci G., Aiello F.C., Szychlinska M.A. et al. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression // Int. J. Mol. Sci. 2015. Vol.16. P. 6093–6112.
23. Aebi H.E. Catalase in Bergmeyer, HU, Methods in enzymatic analysis // Weinheim: Verlag Chemie. 1978. P. 273–286.
24. Olariu L., Pyatigorskaya N., Dumitriu B. et al. In vitro chondro-restitutive capacity of Alflutop® proved on chondrocytes cultures // Romanian Biotechnological Letters. 2016. Vol. 22(6). P. 12047–12053.
25. Olariu L., Dumitriu B., Buse E., Rosoiu N. The in vitro” effect of Alflutop product on some extracellular signaling factors involved in the osteoarthicular pathology inflammation // Analele AOSR. 2015. Vol. 4 (2). P. 7–18.
26. Olariu L., Vacaru A., Pyatigorskaya N. et al. Original romanian product involved in cellular chondro -modulatory mechanisms. Euroinvent medalia de aur // Catalog Euroinvent. 2016. P. 437.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
Previous article
Next article
