Expression of Ptgs2 gene in rat knee cartilage cells under conditions of ostearthritis and with administration of biologically active substances

A. Dranitsina, O. Blohina, O. Korotkyi, K. Dvorshchenko, L. Ostapchenko
ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv; ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv; ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv; ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv; ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv


Osteoarthritis – degenerative-dystrophic cartilage disease, caused by various factors. To date, there is no effective treatment that would provide a full recovery from arthrosis. Chondroprotectors have been used in medicine for a long time, but the raw material for them is a mixture of chondroitin sulfate molecules of varying lengths and variations in the position of sulfate groups, which has different levels of purification, which sometimes causes various undesirable effects. The purpose of the work was to analyze the intensity of free radical processes and the expression of the inflammatory response mediator gene – Ptgs2 in cartilage tissue of rat-induced sodium monoiodoacetate arthrosis and the administration of biologically active substances: chondroitin sulfate, melanin (polyphenolic compound with antioxidant and anti-inflammatory properties), and their combination. The work was performed on white nonlinear rats. Used methods: determination of concentration of organic
hydroperoxides, RT-PCR in real time, statistical methods. The molecular-biochemical analysis of cartilaginous tissue of rat-induced sodium monoiodoacetate by arthrosis showed a 8.1-fold increase in the expression of the Ptgs2 gene (p ≤ 0.001), an increase in free radical processes
(2-fold increase of organic hydroperoxides content (p ≤ 0.001)) in comparison with a control group of animals, indicating a redox cell imbalance, the development of oxidative stress and the activation of inflammatory and destructive processes in the tissue. When using chondroitin sulfate, melanin, and combinations of these biologically active substances under the same conditions, the level of expression of this gene and the content of organic hydroperoxides approached the control values indicating the anti-inflammatory and antioxidant properties of these drugs and the appropriateness of the joint use of chondroitin sulfate and melanin under conditions of osteoarthritis in rats, which, in turn, promotes a faster restoration of the structure of the cartilage tissue and the pattern of expression of certain genes, inhibited degradation of freeradical
processes and lipid peroxidation and inhibits inflammation.


cartilage, osteoarthritis, rats, chondroitin sulfate, Ptgs2, inflammation

Full Text:



Dranitsina A., Dvorshchenko K., Grebinyk D., Ostapchenko L. The impact of oxidative stress on Par2, Ptgs2 genes expression in rat duodenal epithelial cells under conditions of prolonged gastric hypochlorhydria and with administration of multiprobiotic. Journal of Applied Pharmaceutical Science. 2016;6,(12):162-9.

Dranitsina A., Taburets O., Dvorshchenko K., Grebinyk D., Beregova T., Ostapchenko L. Tgfb1, Ptgs2 genes expression during dynamics of wound healing and with the treatment of melanin, Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2017;8(1): 2014-23.

Sandell L., Xing X., Franz C., Davies S., Chang Li-Wei., Patra D. Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1b. Osteoarthritis Cartilage.2008;16(12):1560–71. PMC2605974.

Au R., Al-Talib T., Au AY., Phan P., Frondoza C. Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, iNOS gene expression, and prostaglandin E 2 and nitric oxide production in articular chondrocytes and monocyte/macrophages. Osteoarthritis Cartilage. 2007;15(11):1249-55. PMID: 17845860.

Felson D., Lawrence R., Dieppe P., Hirsch R., Helmick C., Jordan J. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133(8):635-46. PMID: 11033593.

Goldring S., Goldring M., The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;(427 Suppl):S27-36. PMID: 15480070.

Wu K. Cyclooxygenase 2 induction: molecular mechanism and pathophysiologic roles. Am J Pathol. 2004; 165(3): 753–61. PMC1618587.

Benito M., Veale D., FitzGerald O., van den Berg W., Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005;64(9):1263-7.

Dirk P., Beyer A., Koczan D., Wilhelm T., Thiesen Hans-Jürgen., Kinne R. Constitutive upregulation of the transforming growth factor-β pathway in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther. 2007;

(3):R59. PMC2206335.

Ota K., Quint P., Weivoda M., Ruan M., Pederson L., Westendorf J., Khosla S., Oursler M. Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors. Bone. 2013 Nov;57(1):68-75. PMID: 23891907.

Shi-Wen X., Leask A., Abraham D. Regulation and function of connective tissue growth factor/CCN2 in tissue repair, scarring and fibrosis. Cytokine Growth factor Rev. Cytokine Growth Factor Rev. 2008 Apr;19(2):133-44. PMID: 18358427.

Barnes E., Edwards N. Treatment of osteoarthritis. South Med J. 2005;98(2):205-9.

Volpi N. Quality of different chondroitin sulfate preparations in relation to their therapeutic activity. Journal of Pharmacy and Pharmacology. J Pharm Pharmacol. 2009;61(10):1271-80. PMID: 19814858.

Lauder R. Chondroitin sulfate: a complex molecule with potential impacts on a wide range of biological systems. Complement Ther Med. 2009;17(1):56-62. PMID: 19114230.

Largo R., Roman–Blas J., Moreno–Rubio J. Chondroitin sulfate improves synovitis in rabbits with chronic antigen induced arthritis. Osteoarthritis Cartilage. 2010;18(1):17–23. Reference Number: 18.a55e6cc1.1513693884.57da72d7.

Zhang R., Brennan M., Shen Z., MacPherson J., Schmitt D., Molenda C., Hazen S. Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. Osteoarthritis Cartilage. 2010;18 Suppl 1:S17-23. PMID: 20399901.

Caraglia M., Beninati S., Giuberti G., D'Alessandro A., Lentini A., Abbruzzese A. Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice. Exp Mol Med. 2005;37(5):476-81. PMID: 16264272.

Agar N., Young A. Melanogenesis: a photoprotective response to DNA damage? Mutat Res. 2005;571(1-2):121-32. PMID: 15748643.

El-Obeid A., Al-Harbi S., Al-Jomah N., Hassib A. Herbal melanin modulates tumor necrosis factor (TNF-alfa), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production. Phytomedicine, 2006;13:324–33. PMID: 16635740.

Golyshkіn D., Falaleeva T., Neporada K., Beregova T. Effect of melanin on the condition of gastric mucosa and reaction of the hypothalamic-pituitary-adrenal axis under acute stress. Physiological journal


Janusz M., Little C., King L., Hookfin E., Brown K., Heitmeyer S., Caterson B., Poole A., Taiwo Y. Detection of aggrecanase- and MMPgenerated catabolic neoepitopes in the rat iodoacetate model of cartilage degeneration. Osteoarthritis Cartilage. 2004;12(9):720-8. PMID: 15325638.

Jiang Z., Woollard A., Wolff S. Hydrogen peroxide production during experimental protein glycation. FEBS Lett. 1990;268(1):69-71. PMID: 2384174.

Nourooz-Zadeh J., Tajaddini-Sarmadi J., Wolff S. Measurement of plasma hydroperoxide concentrations by the ferrous oxidation – Xylenol Orange assay. Anal Biochem. 1994;220(2):403-9. PMID: 7978285.

Lowry O., Rosebrough N., Farr A., Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75. PMID: 14907713.

Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidiniumthiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9. PMID: 2440339.

Livak К., Schmittgen T. Analysis of relative gene expression data using real time quantitative PCR and method. Methods. 2001;25(4):402-8. PMID: 11846609.

Tikhova Y., Dvorshchenko K., Dranitsina A., Grebinyk D., Korotkyi O., Ostapchenko L. Prooxidant – antioxidant status and Ptgs2, Nos2 genes expression in rat cartilage with osteoarthritis and after the treatment of chondroitin sulfate. RJPBCS. 2017;8(4):994-1001.

Kamata H., Hirata H. Redox regulation of cellular signalling. Cell Signal. 1999;11(1):1-14. PMID: 10206339.

Starkman B., Cravero J., Delcarlo M., Loeser RF IGF-I stimulation of proteoglycan synthesis by chondrocytes requires activation of the PI 3-kinase pathway but not ERK MAPK. Biochem J. 2005;389(Pt 3):723-9. PMID: 15801908.

Haringman J., Smeets T., Reinders-Blankert P., Tak P. Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann Rheum Dis. 2006; 65(3): 294–300. PMC1798063.

Conte A., Volpi N., Palmieri L., Bahous I., Ronca G. Biochemical and pharmacological aspects of oral treatment with chondroitin sulfate. Arzneimittelforschung. 1995;45(8):918-25. PMID: 7575762.

Pelletier J., Martel–Pelletier J., Abramson S. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001;44(6):1237-47. PMID: 11407681.

Chan P., Caron J., Rosa G., Orth M. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthritis Cartilage.

;13(5):387-94. PMID: 15882562.

Jomphe C., Gabriac M., Hale T., Héroux L., Trudeau L., Deblois D., Montell E., Vergés J., du Souich P. Chondroitin sulfate inhibits the nuclear translocation of nuclear factor–kappa B in interleukin–1beta–stimulated chondrocytes. Basic Clin Pharmacol Toxicol. 2008;102(1):59-65. PMID: 17983423.

Tat Kwan S., Pelletier J., Lajeunesse D., Fahmi H., Lavigne M., Martel-Pelletier J. The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in human

osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin Exp Rheumatol. 2008;26(2):295-304. PMID: 18565252.

Taburets O., Morgaienko O., Kondratiuk T., Beregova T., Ostapchenko LI. The Effect of "Melanin-Gel" on the Wound Healing. RJPBCS.2016;7(3):2031–8.

Cui Y., Wang X., Xue J., Liu J., Xie M. Chrysanthemum morifolium extract attenuates high-fat milk-induced fatty liver through peroxisome proliferator-activated receptor alpha-mediated mechanism in mice. Nutr Res. 2014;34(3):268-75. PMID: 24655494.


Received: 05.03.2018

Revised: 09.04.2018

Signed for publication: 09.04.2018



  • There are currently no refbacks.

Лицензия Creative Commons
This journal is available according to the Creative Commons License «Attribution» («Атрибуція») 4.0 Global (CC-BY).