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Trace Elements in Medicine
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SERUM SELENOPROTEIN P LEVEL, GLUTATHIONE PEROXIDASE ACTIVITY, AND OTHER MARKERS OF SELENIUM METABOLISM IN PATIENTS WITH OSTEOARTHRITIS

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ABSTRACT.
Objective – investigation of selenium (Se) metabolism characteristics in patients with knee osteoar-thritis (OA) depending on the presence of comorbid hip osteoarthritis, with assessment of Se levels in biosamples, as well as selenoprotein P (SELENOP) level and glutathione peroxidase (GPX) аactivity in serum.

Materials and methods. During the study 27 patients with knee OA, 45 patients with comorbid knee and hip OA, as well as 37 healthy subjects were examined. Assessment of serum Se was performed using inductively-coupled plasma mass-spectrometry. Evaluation of serum SELENOP, GPX, and cartilage oligomeric matrix protein (COMP) was per-formed using enzyme-linked immunosorbent assay. Assessment of C-reactive protein (CRP) levels was performed us-ing immunoturbidimetry. 

Results. Serum COMP and CRP levels in patients with knee OA and comorbid knee and hip OA exceeded the control values by 123% and 99%, as well as 69% and 127%, respectively. Similarly, hair Se levels and serum GPX concentration in these groups of patients was higher compared to the respective values in healthy controls by 73% and 41%, as well as 31% and 38%. Only an insignificant trend to a decrease in serum Se levels was observed. At the same time, serum concentration of SELENOP, being the major Setransporting protein in blood, in patients with knee OA and comorbid knee and hip OA was lower than that in healthy examinees by 18% and 45%, respectively. 

Conclusions. It is assumed that an increase in serum GPX levels may be a compensatory response to oxidative stress in cartilage damage, whereas a reduction in serum SELENOP in parallel with a trend to lower circulating Se concentration, may be indicative of the formation of Se deficiency in OA due to higher demands of the organism in Se for biosynthesis of antioxidant selenoproteins like GPX.

KEYWORDS:  selenium, selenoproteins, osteoarthritis, knee, hip.

For citation: Skalny A.V., Korobeinikova T.V., Aliyev A.F., Remizova N.I., Morozova G.D., Ternovoy K.S., Kovalenko A.A., Tinkov A.A. Serum selenoprotein P level, glutathione peroxidase activity, and other markers of selenium metabolism in patients with osteoarthritis. Trace elemets in medicine. 2025;26(4):15-24. DOI: 10.19112/2413-6174-2025-26-4-15-24

REFERENCES
Skalny A.V., Korobeynikova T.V., Menshikova I.V., Morozova G.D., Sotnikova T.I., Mak D.V., Tinkov A.A. Association of selenium and selenoprotein metab olism characteristics with cartilage damage intensity in patients with rheumatoid, psoriatic, and gouty arthritis. Problems of biological, medical and pharmaceutical chemistry. 2025; 28(11): 68-76. (In Russian); https://doi.org/10.29296/25877313-2025-11-09.
Akinmade A., Oginni L.M., Adegbehingbe O.O., Okunlola A.I., Jeje O.A., Adeyeye A.I. Serum cartilage oligomeric matrix protein as a biomarker for predicting development and progression of knee osteoarthritis. International Orthopaedics. 2021; 45(3): 551–557; https://doi.org/10.1007/s00264-021-04943-4.
Cao F., Xu Z., Li X.X., Fu Z.Y., Han R.Y., Zhang J.L., Wang P., Hou S., Pan H.F. Trends and cross-country inequalities in the global burden of osteoarthritis, 1990–2019: A population-based study. Ageing Research Reviews. 2024; 99: 102382; https://doi.org/10.1016/j.arr.2024.102382.
Chen Z., Zhong H., Wei J., Lin S., Zong Z., Gong F., Huang X., Sun J., Li P., Lin H., Wei B., Chu J. Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis. Arthritis Research & Therapy. 2019; 21(1): 300; https://doi.org/10.1186/s13075-019-2085-6.
Cheng H.L., Yen C.C., Huang L.W., Hu Y.C., Huang T.C., Hsieh B.S., Chang K.L. Selenium Lessens Osteoarthritis by Protecting Articular Chondrocytes from Oxidative Damage through Nrf2 and NF-κB Pathways. International Journal of Molecular Sciences. 2024; 25(5): 2511; https://doi.org/10.3390/ijms25052511.
Cui A., Li H., Wang D., Zhong J., Chen Y., Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020; 29–30: 100587; https://doi.org/10.1016/j.eclinm.2020.100587.
De Roover A., Escribano-Núñez A., Monteagudo S., Lories R. Fundamentals of osteoarthritis: Inflammatory mediators in osteo-arthritis. Osteoarthritis and Cartilage. 2023; 31(10): 1303–1311; https://doi.org/10.1016/j.joca.2023.06.005.
Deng H., Liu H., Yang Z., Bao M., Lin X., Han J., Qu C. Progress of Selenium Deficiency in the Pathogenesis of Arthropathies and Selenium Supplement for Their Treatment. Biological Trace Element Research. 2022; 200(10): 4238–4249; https://doi.org/10.1007/s12011-021-03022-4.
Deng X., Tan Y. A national cross-sectional analysis of selenium intake and risk of osteoarthritis: NHANES 2003-2016. Frontiers in Public Health. 2023; 10: 1047605; https://doi.org/10.3389/fpubh.2022.1047605.
Fan Z., Yan L., Liu H., Li X., Fan K., Liu Q., Li J.J., Wang B. The prevalence of hip osteoarthritis: a systematic review and meta-analysis. Arthritis Research & Therapy. 2023; 25: 51; https://doi.org/10.1186/s13075-023-03033-7.
GBD 2021 Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Rheumatology. 2023; 5(9): e508–e522; https://doi.org/10.1016/S2665-9913(23)00163-7.
Jacobson G.A., Ives S.J., Narkowicz C., Jones G. Plasma glutathione peroxidase (GSH-Px) concentration is elevated in rheuma-toid arthritis: a case-control study. Clinical Rheumatology. 2012; 31(11): 1543–1547; https://doi.org/10.1007/s10067-012-2046-9.
Kang D., Lee J., Jung J., Carlson B.A., Chang M.J., Chang C.B., Kang S.B., Lee B.C., Gladyshev V.N., Hatfield D.L., Lee B.J., Kim J.H. Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis. Nature Communications. 2022; 13(1): 779; https://doi.org/10.1038/s41467-022-28385-7.
Kang D., Lee J., Wu C., Guo X., Lee B.J., Chun J.S., Kim J.H. The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies. Experimental & Molecular Medicine. 2020; 52(8): 1198–1208; https://doi.org/10.1038/s12276-020-0408-y.
Kieliszek M., Bano I. Selenium as an important factor in various disease states - a review. EXCLI Journal. 2022; 21: 948–966; https://doi.org/10.17179/excli2022-5137.
Kondo F., Takegami Y., Ishizuka S., Hasegawa Y., Imagama S. The association of the progression of knee osteoarthritis with high-sensitivity CRP in community-dwelling people-the Yakumo study. Clinical Rheumatology. 2021; 40(7): 2643–2649; https://doi.org/10.1007/s10067-020-05541-2.
Li G., Cheng T., Yu X. The Impact of Trace Elements on Osteoarthritis. Frontiers in Medicine. 2021; 8: 771297; https://doi.org/10.3389/fmed.2021.771297.
Liu L., Luo P., Wen P., Xu P. Effects of selenium and iodine on Kashin-Beck disease: an updated review. Frontiers in Nutrition. 2024; 11: 1402559; https://doi.org/10.3389/fnut.2024.1402559.
Liu L., Luo P., Yang M., Wang J., Hou W., Xu P. The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review. Frontiers in Molecular Biosciences. 2022; 9: 1001212; https://doi.org/10.3389/fmolb.2022.1001212.
Loeser R.F., Goldring S.R., Scanzello C.R., Goldring M.B. Osteoarthritis: a disease of the joint as an organ. Arthritis & Rheumatism. 2012; 64(6): 1697–1707; https://doi.org/10.1002/art.34453.
Long H., Liu Q., Yin H., Wang K., Diao N., Zhang Y., Lin J., Guo A. Prevalence Trends of Site-Specific Osteoarthritis From 1990 to 2019: Findings From the Global Burden of Disease Study 2019. Arthritis & Rheumatology. 2022; 74(7): 1172–1183; https://doi.org/10.1002/art.42089.
Mollazadeh H., Salesi M. A systematic review and meta-analysis of the association between selenium and osteoarthritis. Immunopathologia Persa. 2024; 11(1): e40656; https://doi.org/10.34172/ipp.2024.40656.
Musumeci G., Aiello F.C., Szychlinska M.A., Di Rosa M., Castrogiovanni P., Mobasheri A. Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression. International Journal of Molecular Sciences. 2015; 16(3): 6093–6112; https://doi.org/10.3390/ijms16036093.
Paździor M., Kiełczykowska M., Kurzepa J., Luchowska-Kocot D., Kocot J., Musik I. The Oxidative Stress in Knee Osteoarthritis Patients. An Attempt of Evaluation of Possible Compensatory Effects Occurring in the Disease Development. Medicina. 2019; 55(5): 150; https://doi.org/10.3390/medicina55050150.
Pietschmann N., Rijntjes E., Hoeg A., Stoedter M., Schweizer U., Seemann P., Schomburg L. Selenoprotein P is the essential selenium transporter for bones. Metallomics. 2014; 6(5): 1043–1049; https://doi.org/10.1039/c4mt00003j.
Pyrzyńska K. Determination of selenium species in environmental samples. Microchimica Acta. 2002; 140(1): 55–62; https://doi.org/10.1007/s00604-002-0893-9.
Schomburg L. Selenoprotein P – Selenium transport protein, enzyme and biomarker of selenium status. Free Radical Biology and Medicine. 2022; 191: 150–163; https://doi.org/10.1016/j.freeradbiomed.2022.08.022.
Skalny A.V., Simashkova N.V., Skalnaya A.A., Klyushnik T.P., Bjørklund G., Skalnaya M.G., Tinkov A.A. Assessment of gender and age effects on serum and hair trace element levels in children with autism spectrum disorder. Metabolic Brain Disease. 2017; 32(5): 1675–1684; https://doi.org/10.1007/s11011-017-0056-7.
Smith M.M., Melrose J. COMP Is a Biomarker of Cartilage Destruction, Extracellular Matrix and Vascular Remodeling and Tissue Repair. International Journal of Molecular Sciences. 2025; 26(18): 9182; https://doi.org/10.3390/ijms26189182.
Sun W., Wang X., Zou X., Song R., Du X., Hu J., Xiong Y. Selenoprotein P gene r25191g/a polymorphism and quantification of selenoprotein P mRNA level in patients with Kashin-Beck disease. British Journal of Nutrition. 2010; 104(9): 1283–1287; https://doi.org/10.1017/S0007114510002199.
Tinkov A.A., Skalny A.V., Guo X., Korobeinikova T.V., Ning Y., Rocha J.B.T., Zhang F., Aschner M. Review of the Protective Effects of Selenium against T-2 Toxin-Induced Toxicity. Chemical Research in Toxicology. 2025; 38(6): 975–996; https://doi.org/10.1021/acs.chemrestox.5c00095.
Turrubiates-Hernández F.J., Márquez-Sandoval Y.F., González-Estevez G., Reyes-Castillo Z., Muñoz-Valle J.F. The Relevance of Selenium Status in Rheumatoid Arthritis. Nutrients. 2020; 12(10): 3007; https://doi.org/10.3390/nu12103007.
Verma P., Dalal K. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. Journal of Orthopaedic Research. 2013; 31(7): 999–1006; https://doi.org/10.1002/jor.22324.
Vnukov V.V., Panina S.B., Krolevets I.V., Milutina N.P., Ananyan A.A., Zabrodin M.A., Plotnikov A.A. Specificities of oxida-tive stress in the blood and synovial fluid in knee osteoarthritis. Advances in Gerontology. 2015; 5(4): 261–266; https://doi.org/10.1134/S207905701504014X.
Wahl L., Chillon T.S., Seemann P., Ohrndorf S., Ochwadt R., Becker W., Schomburg L., Hoff P. Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis. The Journal of Nutritional Biochemistry. 2025; 135: 109776; https://doi.org/10.1016/j.jnutbio.2024.109776.
Wang N., Xie M., Lei G., Zeng C., Yang T., Yang Z., Wang Y., Li J., Wei J., Tian J., Yang T. A Cross-Sectional Study of Association between Plasma Selenium Levels and the Prevalence of Osteoarthritis: Data from the Xiangya Osteoarthritis Study. The Journal of Nutrition, Health & Aging. 2022; 26(2): 197–202; https://doi.org/10.1007/s12603-022-1739-2.
Wang Y., Liu Z., Wu H., Wang C. C-reactive protein as a mediator in the link between cardiometabolic index and osteoarthritis: insights from NHANES 2001-2010. Lipids in Health and Disease. 2025; 24(1): 231; https://doi.org/10.1186/s12944-025-02603-9.
Wei W., Qi X., Cheng B., He D., Qin X., Zhang N., Zhao Y., Chu X., Shi S., Cai Q., Yang X., Cheng S., Meng P., Hui J., Pan C., Zhao B., Liu L., Wen Y., Liu H., Jia Y., Zhang F. An atlas of causal association between micronutrients and osteoarthritis. Preven-tive Medicine. 2024; 185: 108063; https://doi.org/10.1016/j.ypmed.2024.108063.
Yan J., Zheng Y., Min Z., Ning Q., Lu S. Selenium effect on selenoprotein transcriptome in chondrocytes. Biometals. 2013; 26(2): 285–296; https://doi.org/10.1007/s10534-013-9610-x.
Zhang R., Yang A., Zhang J., Kang W., Li J., Yuan P., Dong B., Shi C., Xiong Y. Expression of 13 selenoprotein genes in osteoarthritis patients by microarray–evidence from a meta-analysis. Osteoarthritis and Cartilage. 2018; 26: S345; https://doi.org/10.1016/j.joca.2018.02.686.
Zhang S., Zhong Y., Wang X., Jiang W., Chen X., Kang Y., Li Z., Liao W., Zheng L., Sheng P., Zhang Z. Association of peripheral inflammatory indicators with osteoarthritis risk. Osteoarthritis and Cartilage Open. 2024; 6(3): 100496; https://doi.org/10.1016/j.ocarto.2024.100496.
Zhao Q., Tang Y., Zhang L., Sun N., Liu Q., Zhang R. Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis. Journal of Inflammation Research. 2023; 16: 183-196; https://doi.org/10.2147/JIR.S388934.

Information about the authors:

Anatoly V. Skalny – Dr.Sc. (Med.), Professor, Director of the Center for Bioelementology and Human Ecology1; 
Head of the Department of Medical Elementology2 
E-mail: avskalny@gmail.com; ORCID: 0000-0001-7838-1366

Tatiana V. Korobeinikova – Ph.D. (Tech.), Head of the Laboratory of Molecular Dietetics, 
Center for Bioelementology and Human Ecology1; Associate Professor of the Department of Medical Elementology2
E-mail: tatcvetk@yandex.ru; ORCID: 0000-0002-1373-6354

Ali F. Aliyev – Traumatologist Orthopedist, Department of Medical Rehabilitation, University Clinical Hospital № 2 
E-mail: dr.aliev90@gmail.com

Nelli I. Remizova – Physiatrist, Department of Medical Rehabilitation, University Clinical Hospital № 2 
E-mail: nelly13m@mail.ru

Galina D. Morozova – Laboratory Assistant, Laboratory of Molecular Dietetics, 
Center for Bioelementology and Human Ecology
E-mail: morozova0826@gmail.com; ORCID: 0000-0001-8600-902X

Konstantin S. Ternovoy – Ph.D. (Med.), Head of Department of Medical Rehabilitation, 
University Clinical Hospital № 2
E-mail: Ternovoy_k_s@staff.sechenov.ru

Alexey A. Kovalenko – Ph.D. (Med.), Director of University Clinical Hospital № 2, 
Associate Professor of the Department of Sports Medicine and Medical Rehabilitation 
E-mail: alexey-kovalenko@yandex.ru 

Alexey A. Tinkov – Dr.Sc. (Med.), Principal Investigator of the Center for Bioelementology and Human Ecology1; 
Professor of the Department of Medical Elementology2
E-mail: tinkov.a.a@gmail.com; ORCID: 0000-0003-0348-6192

Conflict of interest 
The authors declare no obvious and potential conflicts of interest related to the publication of this article.

Funding
The study was performed with the financial support of the Russian Science Foundation (project No. 24-45-00073).

Поступила 10 ноября 2025 года
Принята к публикации 1 декабря 2025 года