Proinflammatory cytokines, chemokine CXCL17 and heat shock proteins in osteoarthritis of the knee joint

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Abstract

Osteoarthritis (OA), a common multifactorial disease of musculoskeletal system, is one of the leading causes of disability in the population. One of the most important pathogenetic factors of OA is a shift of cytokine profile towards pro-inflammatory state. Their increased levels lead to dysfunction of cartilage tissue cells with its damage. Purpose of the present study was to evaluate diagnostic significance of the most important cytokine and chemokine levels involved in pathogenesis of OA.

The study involved 50 patients undergoing inpatient treatment at the “Hospital for War Veterans” (Vladivostok) with an established OA of the knee joints. The following mediators involved in the development of inflammation have been determined: interleukins IL-1â, IL-6, chemokine CXCL17, tumor necrosis factor TNFá and heat shock proteins HSP27, HSP70 in blood serum of patients being analyzed by ELISA test systems. It has been shown that the levels of interleukins IL-1â and IL-6, TNFá and CXCL17 in patients with OA exceeded those for healthy individuals. The levels of cytokines IL- 1â, IL-6, chemokine CXCL17 and TNFá in blood serum of OA patients were 7.4 (6.4-8.9), 33.7 (26.5-68.4); 33.8 (29.8- 61.0) and 6.5 (4.94-8.59) pg/ml, respectively, thus significantly exceeding the values for healthy person s (1.3 (1.2-1.4), 5.8 (4.2-6.3), 24.9 (19, 1-29.9) and 2.7 (2.1-3.1) pg/ml, p < 0.05). In OA patients, the concentration of TNFá had a direct relationship with the chemokine CXCL17 (r = 0.83, p < 0.05). The concentrations of heat shock proteins HSP27, HSP70 and their ratio were significantly lower in patients with OA compared to the control group (respectively: z = -3.06, p = 0.002; z = -4.41, p = 0.00001; z = -2.05, p = 0.04), thus allowing us to suggest the tolerance of chondrocytes to the influence of cytokines. At the same time, the concentration of HSP70 decreased as the disease progressed, while the level of HSP27 did not change significantly. Thus, determining the level of systemic intercellular mediators enables usage of these indexes as potential biochemical markers for predicting severity of the disease and assessing their fundamental role in pathogenesis of knee OA.

About the authors

N. G. Plekhova

Pacific State Medical University

Author for correspondence.
Email: pl_nat@hotmail.com

PhD, MD (Biology), Associate Professor, Head, Interdisciplinary Research Center

Russian Federation, Vladivostok

M. A. Kabalyk

Pacific State Medical University

Email: pl_nat@hotmail.com

PhD (Medicine), Associate Professor, Leading Research Associate, Interdisciplinary Research Center

Russian Federation, Vladivostok

E. V. Prosekova

Pacific State Medical University

Email: pl_nat@hotmail.com

PhD, MD (Medicine), Professor, Head, Department of Clinical Laboratory Diagnostics, General and Clinical Immunology

Russian Federation, Vladivostok

V. B. Shumatov

Pacific State Medical University

Email: pl_nat@hotmail.com

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Department of Anesthesiology, Resuscitation, Intensive Care and Emergency Medical Care

Russian Federation, Vladivostok

References

  1. Кабалык М.А. Биомаркеры и участники ремоделирования субхондральной кости при остеоартрозе // Тихоокеанский медицинский журнал, 2017. Т. 1. С. 36-41. [Kabalyk M.A. Biomarkers of subchondral bone remodeling in osteoarthritis. Tikhookeanskiy meditsinskiy zhurnal = Pacific Medical Journal, 2017, Vol. 1, pp. 36-41.
  2. Grässel S., Zaucke F., Madry H. Osteoarthritis: novel molecular mechanisms increase our understanding of the disease pathology. J. Clin. Med., 2021, Vol. 10, no. 9, 1938. doi: 10.3390/jcm10091938.
  3. Giblin S.P., Ranawana S., Hassibi S., Birchenough H.L., Mincham K.T., Snelgrove R.J., Tsuchiya T., Kanegasaki S., Dyer D., Pease J.E. CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling. Front. Immunol., 2023, Vol. 14, 1254697. doi: 10.3389/fimmu.2023.1254697.
  4. Gowhari Shabgah A., Jadidi-Niaragh F., Ebrahimzadeh F., Mohammadi H., Askari E., Pahlavani N., Malekahmadi M., Nik M.E., Navashenaq J.G. A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation. Cell. Biol. Int., 2022, Vol. 46, no 10, pp. 1557-1570.
  5. Goekoop R.J., Kloppenburg M., Kroon H.M., Frölich M., Huizinga T.W., Westendorp R.G., Gussekloo J. Low innate production of interleukin-1beta and interleukin-6 is associated with the absence of osteoarthritis in old age. Osteoarthritis Cartilage, 2010, Vol. 18, no 7, pp. 942-947.
  6. Ishimoto R., Mutsuzaki H., Shimizu Y., Yoshikawa K., Koseki K., Takeuchi R., Matsumoto S., Hada Y. Association between obesity and short-term patient-reported outcomes following total knee arthroplasty: a retrospective cohort study in Japan. J. Clin. Med., 2024, Vol. 13, no. 5, 1291. doi: 10.3390/jcm13051291.
  7. Kaufman J., Caric D., Vukojevic K. Expression pattern of Syndecan-1 and HSP-70 in hip tissue of patients with osteoarthritis. J. Orthop., 2019, Vol. 17, pp. 134-138.
  8. Kapoor M., Martel-Pelletier J., Lajeunesse D., Pelletier J.P., Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol., 2011, Vol. 7, no 1, pp. 33-42.
  9. Liao Y., Ren Y., Luo X., Mirando A.J., Long J.T., Leinroth A., Ji R.R., Hilton M.J. Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner. Sci. Signal., 2022, Vol. 15, no. 744, eabn7082. doi: 10.1126/scisignal.abn7082.
  10. Molnar V., Matišić V., Kodvanj I., Bjelica R., Jeleč Ž., Hudetz D., Rod E., Čukelj F., Vrdoljak T., Vidović D., Starešinić M., Sabalić S., Dobričić B., Petrović T., Antičević D., Borić I., Košir R., Zmrzljak U.P., Primorac D. Cytokines and chemokines involved in osteoarthritis pathogenesis. Int. J. Mol. Sci., 2021, Vol. 22, no. 17, 9208. doi: 10.3390/ijms22179208.
  11. Ngarmukos S., Scaramuzza S., Theerawattanapong N., Tanavalee A., Honsawek S. Circulating and synovial fluid Heat Shock Protein 70 are correlated with severity in knee osteoarthritis. Cartilage, 2020, Vol. 11, no. 3, pp. 323-328.
  12. Tan S., Fang W., Vangsness C.T. Jr., Han B. Influence of cellular microenvironment on human articular chondrocyte cell signaling. Cartilage, 2021, Vol. 13, no. 2_suppl, pp. 935S-946S.
  13. Teunis T., Beekhuizen M., Van Osch G.V., 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, pp. 146-150.
  14. Vangness C.T., BurkeW.S., NarvyW.S., MacPhee R.D., Fedenko A.N. Human knee synovial fluid cytokines correlated with grade of knee osteoarthritis – A pilot study. Bull. NYU Hosp. Jt Dis., 2011, Vol. 69, pp. 122-127.
  15. Zhang J., Li K., Qiu X. Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization. Front. Immunol., 2024, Vol. 18, no. 15, 1362012. doi: 10.3389/fimmu.2024.1362012.

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2. Figure 1. Сontent of interleukins IL-1 (A), IL-6 (B), chemokine CXCL17 (C) and tumor necrosis factor TNF (D) in blood serum

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Copyright (c) 2024 Plekhova N.G., Kabalyk M.A., Prosekova E.V., Shumatov V.B.

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