{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:05:55Z","timestamp":1793736355257,"version":"4.6.1"},"reference-count":101,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Osteoarthritis (OA) is a prevalent and disabling joint disorder characterized by progressive cartilage degradation, subchondral bone changes, synovial inflammation, and chronic pain. While traditionally attributed to mechanical and age-related factors, increasing attention has been directed toward the role of nutritional components in disease modulation. This article critically examines the emerging role of three essential trace elements, zinc, copper, and selenium, in the pathophysiology of OA. These micronutrients are fundamental to antioxidant defense, immune modulation, and extracellular matrix (ECM) integrity. Altered systemic or local levels of zinc, copper, and selenium have been associated with oxidative stress, inflammation, and dysregulated cartilage metabolism in OA. Drawing on clinical studies, in vivo and in vitro experimental models, and population-based data, we synthesize evidence on trace element status in OA patients, mechanistic pathways, and therapeutic potential, including emerging nanomedicine strategies that enhance the targeted delivery and therapeutic efficacy of trace elements in joint tissues. This review highlights the need for integrated trace element profiling in OA research and clinical care and supports the exploration of targeted nutritional interventions in OA prevention and management.<\/jats:p>","DOI":"10.3390\/nu17132069","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:39:26Z","timestamp":1750649966000},"page":"2069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Elemental Influence: The Emerging Role of Zinc, Copper, and Selenium in Osteoarthritis"],"prefix":"10.3390","volume":"17","author":[{"given":"Abebe Feyissa","family":"Amhare","sequence":"first","affiliation":[{"name":"Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Schools of Public Health, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Schools of Nursing, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0843-6899","authenticated-orcid":false,"given":"Haobiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Schools of Public Health, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-0846","authenticated-orcid":false,"given":"Lichun","family":"Qiao","sequence":"additional","affiliation":[{"name":"Schools of Public Health, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-3581","authenticated-orcid":false,"given":"Huan","family":"Deng","sequence":"additional","affiliation":[{"name":"Schools of Public Health, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-0114","authenticated-orcid":false,"given":"Jing","family":"Han","sequence":"additional","affiliation":[{"name":"Schools of Public Health, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Global Health Institute, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 712000, China"},{"name":"Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","article-title":"Osteoarthritis","volume":"11","author":"Tang","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101855","DOI":"10.1016\/j.berh.2023.101855","article-title":"Clinical aspects and outcomes in osteoarthritis","volume":"37","year":"2023","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, Z., Xiao, Z., Sun, C., Xu, G., and He, J. (2024). Global, regional and national burden of osteoarthritis in 1990-2021: A systematic analysis of the global burden of disease study 2021. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-08122-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kapoor, M. (2015). Pathogenesis of osteoarthritis. Osteoarthritis: Pathogenesis, Diagnosis, Available Treatments, Drug Safety, Regenerative and Precision Medicine, Springer.","DOI":"10.1007\/978-3-319-19560-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.rehab.2016.07.004","article-title":"An update on the pathophysiology of osteoarthritis","volume":"59","author":"Mobasheri","year":"2016","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, G., Cheng, T., and Yu, X. (2021). The Impact of Trace Elements on Osteoarthritis. Front. Med., 8.","DOI":"10.3389\/fmed.2021.771297"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hu, W., Yao, X., Li, Y., Li, J., Zhang, J., Zou, Z., Kang, F., and Dong, S. (2023). Injectable hydrogel with selenium nanoparticles delivery for sustained glutathione peroxidase activation and enhanced osteoarthritis therapeutics. Mater. Today Bio, 23.","DOI":"10.1016\/j.mtbio.2023.100864"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sanna, A., Firinu, D., Zavattari, P., and Valera, P. (2018). Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis. Nutrients, 10.","DOI":"10.3390\/nu10010068"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cuffaro, D., Gimeno, A., Bernardoni, B.L., Di Leo, R., Pujadas, G., Garcia-Vallv\u00e9, S., Nencetti, S., Rossello, A., and Nuti, E. (2023). Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241311098"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1042\/EBC20180050","article-title":"Lysyl oxidases: From enzyme activity to extracellular matrix cross-links","volume":"63","author":"Vallet","year":"2019","journal-title":"Essays Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Handy, D.E., Joseph, J., and Loscalzo, J. (2021). Selenium, a Micronutrient That Modulates Cardiovascular Health via Redox Enzymology. Nutrients, 13.","DOI":"10.3390\/nu13093238"},{"key":"ref_13","first-page":"123","article-title":"Selenium-dependent glutathione peroxidase and other selenoproteins: Their synthesis and biochemical roles","volume":"68","author":"Gamble","year":"1997","journal-title":"J. Chem. Technol. Biotechnol. Int. Res. Process Environ. Clean Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s12011-024-04197-2","article-title":"Meta-analysis of the Relationship Between Zinc and Copper in Patients with Osteoarthritis","volume":"203","author":"Zhou","year":"2025","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5662","DOI":"10.1007\/s12011-023-03636-w","article-title":"The Daily Intake Levels of Copper, Selenium, and Zinc Are Associated with Osteoarthritis but Not with Rheumatoid Arthritis in a Cross-sectional Study","volume":"201","author":"Yang","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1437S","DOI":"10.1093\/jn\/130.5.1437S","article-title":"Function and Mechanism of Zinc Metalloenzymes","volume":"130","author":"McCall","year":"2000","journal-title":"J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1021\/bi4016617","article-title":"Designing Hydrolytic Zinc Metalloenzymes","volume":"53","author":"Zastrow","year":"2014","journal-title":"Biochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10787-017-0309-4","article-title":"Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-\u03baB signaling","volume":"25","author":"Jarosz","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yao, G., Wang, Z., Xie, R., Zhanghuang, C., and Yan, B. (2024). Trace element zinc metabolism and its relation to tumors. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1457943"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00204-024-03891-3","article-title":"Zinc and its binding proteins: Essential roles and therapeutic potential","volume":"99","author":"Kiouri","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wessels, I., Maywald, M., and Rink, L. (2017). Zinc as a Gatekeeper of Immune Function. Nutrients, 9.","DOI":"10.3390\/nu9121286"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11926-013-0375-6","article-title":"Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis","volume":"15","author":"Houard","year":"2013","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10202","DOI":"10.1073\/pnas.0913897107","article-title":"Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways","volume":"107","author":"Otsuki","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","unstructured":"Nabavi, S.M., and Silva, A.S. (2022). Chapter 2.7\u2014Superoxide dismutase. Antioxidants Effects in Health, Elsevier."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Valentine, J.S., Ellerby, L.M., Graden, J.A., Nishida, C.R., and Gralla, E.B. (1995). Copper-Zinc Superoxide Dismutase: Mechanistic and Biological Studies. Bioinorganic Chemistry: An Inorganic Perspective of Life, Springer.","DOI":"10.1007\/978-94-011-0255-1_8"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Marreiro, D.D., Cruz, K.J., Morais, J.B., Beserra, J.B., Severo, J.S., and de Oliveira, A.R. (2017). Zinc and Oxidative Stress: Current Mechanisms. Antioxidants, 6.","DOI":"10.3390\/antiox6020024"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1039\/C5FO00630A","article-title":"Zinc as a micronutrient and its preventive role of oxidative damage in cells","volume":"6","author":"Kloubert","year":"2015","journal-title":"Food Funct."},{"key":"ref_28","first-page":"37","article-title":"Actividad de la enzima antioxidante super\u00f3xido dismutasa y niveles de cobre y zinc en pacientes con diabetes mellitus tipo 2","volume":"26","author":"Bravo","year":"2007","journal-title":"Arch. Venez. Farmacol. Ter."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Prasad, A.S. (2014). Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health. Front. Nutr., 1.","DOI":"10.3389\/fnut.2014.00014"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Huang, T.C., Chang, W.T., Hu, Y.C., Hsieh, B.S., Cheng, H.L., Yen, J.H., Chiu, P.R., and Chang, K.L. (2018). Zinc Protects Articular Chondrocytes through Changes in Nrf2-Mediated Antioxidants, Cytokines and Matrix Metalloproteinases. Nutrients, 10.","DOI":"10.3390\/nu10040471"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jtemb.2018.08.007","article-title":"Calcium, magnesium, zinc and lead concentrations in the structures forming knee joint in patients with osteoarthritis","volume":"50","author":"Kot","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"He, H., Huang, C., Huang, H., Lan, N., Liu, S., Luo, Y., Zheng, L., Liu, G., Qin, Z., and Zhao, J. (2025). Zn2+-driven metformin conjugated with siRNA attenuates osteoarthritis progression by inhibiting NF-\u03baB signaling and activating autophagy. Biomaterials, 319.","DOI":"10.1016\/j.biomaterials.2025.123210"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.joca.2015.07.016","article-title":"Reciprocal activation of hypoxia-inducible factor (HIF)-2\u03b1 and the zinc-ZIP8-MTF1 axis amplifies catabolic signaling in osteoarthritis","volume":"24","author":"Lee","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"108063","DOI":"10.1016\/j.ypmed.2024.108063","article-title":"An atlas of causal association between micronutrients and osteoarthritis","volume":"185","author":"Wei","year":"2024","journal-title":"Prev. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12937-025-01100-0","article-title":"Mendelian randomization of serum micronutrients and osteoarthritis risk: Focus on zinc","volume":"24","author":"Zeng","year":"2025","journal-title":"Nutr. J."},{"key":"ref_36","first-page":"359","article-title":"Serum Levels of Some Essential Trace Elements in Patients with Osteoarthritis","volume":"27","author":"Ajileye","year":"2024","journal-title":"Afr. J. Biomed. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"D\u0105browski, M., Zio\u0142a-Frankowska, A., Frankowski, M., Kaczmarczyk, J., and Kubaszewski, \u0141. (2021). Comparison of Bone Tissue Trace Element Content in the Different Radiological Stages of Hip Osteoarthritis. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18063260"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1136\/annrheumdis-2014-206752","article-title":"Differential DNA methylation and expression of inflammatory and zinc transporter genes defines subgroups of osteoarthritic hip patients","volume":"74","author":"Rushton","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/jmf.2017.4034","article-title":"The Combination of Probiotic Complex, Rosavin, and Zinc Improves Pain and Cartilage Destruction in an Osteoarthritis Rat Model","volume":"21","author":"Kwon","year":"2018","journal-title":"J. Med. Food"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Asensio, G., Benito-Garz\u00f3n, L., Ram\u00edrez-Jim\u00e9nez, R.A., Guadilla, Y., Gonzalez-Rubio, J., Abradelo, C., Parra, J., Mart\u00edn-L\u00f3pez, M.R., Aguilar, M.R., and V\u00e1zquez-Lasa, B. (2021). Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr\/Zn Folates for Osteochondral Tissue Engineering. Polymers, 14.","DOI":"10.3390\/polym14010012"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/bit.27173","article-title":"Biodegradable zinc oxide composite scaffolds promote osteochondral differentiation of mesenchymal stem cells","volume":"117","author":"Khader","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"You, X., Ye, Y., Lin, S., Zhang, Z., Guo, H., and Ye, H. (2024). Identification of key genes and immune infiltration in osteoarthritis through analysis of zinc metabolism-related genes. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-07347-8"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ruiz, L.M., Libedinsky, A., and Elorza, A.A. (2021). Role of copper on mitochondrial function and metabolism. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.711227"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1177\/1535370216648805","article-title":"Copper, iron, and selenium dietary deficiencies negatively impact skeletal integrity: A review","volume":"241","author":"Medeiros","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.mam.2005.07.015","article-title":"Copper, oxidative stress, and human health","volume":"26","author":"Keen","year":"2005","journal-title":"Mol. Asp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lin, W., Xu, L., and Li, G. (2020). Molecular insights into lysyl oxidases in cartilage regeneration and rejuvenation. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00359"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/jcb.10413","article-title":"Lysyl oxidase: Properties, specificity, and biological roles inside and outside of the cell","volume":"88","author":"Kagan","year":"2003","journal-title":"J. Cell Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yu, Q., Xiao, Y., Guan, M., Zhang, X., Yu, J., Han, M., and Li, Z. (2024). Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1472492"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0300-483X(03)00159-8","article-title":"Copper toxicity, oxidative stress, and antioxidant nutrients","volume":"189","author":"Gaetke","year":"2003","journal-title":"Toxicology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1064S","DOI":"10.1093\/ajcn\/67.5.1064S","article-title":"Copper and immunity","volume":"67","author":"Percival","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1749-6632.1990.tb00142.x","article-title":"The immune response in copper deficiency","volume":"587","author":"Lukasewycz","year":"1990","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Guan, T., Wu, Z., Xu, C., and Su, G. (2023). The association of trace elements with arthritis in US adults: NHANES 2013\u20132016. J. Trace Elem. Med. Biol., 76.","DOI":"10.1016\/j.jtemb.2022.127122"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1007\/s12011-023-03801-1","article-title":"Circulating Copper Is Associated with Inflammatory Biomarkers in Greek Older Adults with Osteoarthritis","volume":"202","author":"Amerikanou","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s12011-016-0927-5","article-title":"Factors that Affect the Content of Cadmium, Nickel, Copper and Zinc in Tissues of the Knee Joint","volume":"178","author":"Roczniak","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pasco, J.A., Anderson, K.B., Williams, L.J., Stuart, A.L., Hyde, N.K., and Holloway-Kew, K.L. (2024). Dietary intakes of copper and selenium in association with bone mineral density. Nutrients, 16.","DOI":"10.3390\/nu16162777"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Saati, A.A., and Adly, H.M. (2023). Assessing the correlation between blood trace element concentrations, picky eating habits, and intelligence quotient in school-aged children. Children, 10.","DOI":"10.3390\/children10071249"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ha, J.-H., Doguer, C., Wang, X., Flores, S.R., and Collins, J.F. (2016). High-iron consumption impairs growth and causes copper-deficiency anemia in weanling Sprague-Dawley rats. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161033"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wang, X., Cai, Y., Wu, C., Liang, J., Tang, K., Lin, Z., Chen, L., Lu, Y., and Wang, Q. (2023). Conversion of senescent cartilage into a pro-chondrogenic microenvironment with antibody-functionalized copper sulfate nanoparticles for efficient osteoarthritis therapy. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-02036-5"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"113583","DOI":"10.1016\/j.jconrel.2025.113583","article-title":"Copper silicate nanoparticle-mediated delivery of astragaloside-IV for osteoarthritis treatment by remodeling the articular cartilage microenvironment","volume":"381","author":"Yang","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_60","first-page":"1491","article-title":"Effect of a topical copper indomethacin gel on inflammatory parameters in a rat model of osteoarthritis","volume":"9","author":"Yassin","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gao, H., Ning, E., Zhang, X., Shao, Z., Hu, D., Bai, L., Che, H., and Hao, Y. (2025). Injectable microspheres filled with copper-containing bioactive glass improve articular cartilage healing by regulating inflammation and recruiting stem cells. Regen. Biomater., 12.","DOI":"10.1093\/rb\/rbae142"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109855","DOI":"10.1016\/j.compositesb.2022.109855","article-title":"Neutrophil-erythrocyte hybrid membrane-coated hollow copper sulfide nanoparticles for targeted and photothermal\/ anti-inflammatory therapy of osteoarthritis","volume":"237","author":"Xue","year":"2022","journal-title":"Compos. Part B Eng."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"C679","DOI":"10.1152\/ajpcell.00573.2024","article-title":"Regulation of fibroblast phenotype in osteoarthritis using CDKN1A-loaded copper sulfide nanoparticles delivered by mesenchymal stem cells","volume":"328","author":"Liu","year":"2025","journal-title":"Am. J. Physiol.\u2014Cell Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e943738","DOI":"10.12659\/MSM.943738","article-title":"The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in Osteoarthritis","volume":"30","author":"Geng","year":"2024","journal-title":"Med. Sci. Monit."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Han, J., Luo, J., Wang, C., Kapilevich, L., and Zhang, X.A. (2024). Roles and mechanisms of copper homeostasis and cuproptosis in osteoarticular diseases. Biomed. Pharmacother., 174.","DOI":"10.1016\/j.biopha.2024.116570"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e39828","DOI":"10.1097\/MD.0000000000039828","article-title":"The effect of copper and vitamin D on osteoarthritis outcomes: A Mendelian randomization study","volume":"103","author":"Luo","year":"2024","journal-title":"Medicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.joca.2021.02.564","article-title":"Genetically predicted circulating levels of copper and zinc are associated with osteoarthritis but not with rheumatoid arthritis","volume":"29","author":"Zhou","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gelpi, R.J., Boveris, A., and Poderoso, J.J. (2016). The Concept of Oxidative Stress After 30 Years. Biochemistry of Oxidative Stress: Physiopathology and Clinical Aspects, Springer International Publishing.","DOI":"10.1007\/978-3-319-45865-6"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/S0140-6736(11)61452-9","article-title":"Selenium and human health","volume":"379","author":"Rayman","year":"2012","journal-title":"Lancet"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.procbio.2024.12.028","article-title":"Understanding selenoproteins: Structural insights, biological functions and transformative applications in therapeutics","volume":"150","author":"Prasad","year":"2025","journal-title":"Process Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Roh, Y.J., Han, S.J., Park, I., Lee, H.M., Ok, Y.S., Lee, B.C., and Lee, S.R. (2020). Role of Selenoproteins in Redox Regulation of Signaling and the Antioxidant System: A Review. Antioxidants, 9.","DOI":"10.3390\/antiox9050383"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cheng, H.L., Yen, C.C., Huang, L.W., Hu, Y.C., Huang, T.C., Hsieh, B.S., and Chang, K.L. (2024). Selenium Lessens Osteoarthritis by Protecting Articular Chondrocytes from Oxidative Damage through Nrf2 and NF-\u03baB Pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052511"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1089\/ars.2011.4145","article-title":"The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities","volume":"16","author":"Huang","year":"2012","journal-title":"Antioxid. Redox Signal"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.2147\/DDDT.S407122","article-title":"The Protective Effect of Selenium Nanoparticles in Osteoarthritis: In vitro and in vivo Studies","volume":"17","author":"Li","year":"2023","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/mnfr.200700330","article-title":"The influence of selenium on immune responses","volume":"52","author":"Hoffmann","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1007\/s12011-021-03022-4","article-title":"Progress of Selenium Deficiency in the Pathogenesis of Arthropathies and Selenium Supplement for Their Treatment","volume":"200","author":"Deng","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s12603-022-1739-2","article-title":"A Cross-Sectional Study of Association between Plasma Selenium Levels and the Prevalence of Osteoarthritis: Data from the Xiangya Osteoarthritis Study","volume":"26","author":"Wang","year":"2022","journal-title":"J. Nutr. Health Aging"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1136\/annrheumdis-2024-eular.2320","article-title":"AB0522 Selenium Status in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Juvenile Idiopathic Arthritis","volume":"83","author":"Wahl","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wahl, L., Samson Chillon, T., Seemann, P., Ohrndorf, S., Ochwadt, R., Becker, W., Schomburg, L., and Hoff, P. (2025). Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis. J. Nutr. Biochem., 135.","DOI":"10.1016\/j.jnutbio.2024.109776"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ning, Y., Hu, M., Diao, J., Gong, Y., Huang, R., Chen, S., Zhang, F., Liu, Y., Chen, F., and Zhang, P. (2022). Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.773534"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/s12276-020-0408-y","article-title":"The role of selenium metabolism and selenoproteins in cartilage homeostasis and arthropathies","volume":"52","author":"Kang","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1007\/s12011-021-02778-z","article-title":"Effectiveness of Selenium on Chondrocyte Glycoprotein Glycosylation Which Play Important Roles in the Pathogenesis of an Endemic Osteoarthritis, Kashin\u2013Beck Disease","volume":"200","author":"Wang","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"125568","DOI":"10.1016\/j.ijpharm.2025.125568","article-title":"Therapeutic potential of Polydopamine-Coated selenium nanoparticles in Osteoarthritis treatment","volume":"675","author":"Park","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Liu, J., Liu, J., Liu, S., Xiao, P., Du, C., Zhan, J., Chen, Z., Chen, L., Li, K., and Huang, W. (2025). Cascade targeting selenium nanoparticles-loaded hydrogel microspheres for multifaceted antioxidant defense in osteoarthritis. Biomaterials, 318.","DOI":"10.1016\/j.biomaterials.2025.123195"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1093\/rheumatology\/keaa622","article-title":"Causal relationship of serum nutritional factors with osteoarthritis: A Mendelian randomization study","volume":"60","author":"Qu","year":"2021","journal-title":"Rheumatology"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chandrapalan, T., and Kwong, R.W.M. (2021). Functional significance and physiological regulation of essential trace metals in fish. J. Exp. Biol., 224.","DOI":"10.1242\/jeb.238790"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00360-024-01565-1","article-title":"Trace metals in the teleost fish gill: Biological roles, uptake regulation, and detoxification mechanisms","volume":"194","author":"Kwong","year":"2024","journal-title":"J. Comp. Physiol. B"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"L172","DOI":"10.1152\/ajplung.2001.281.1.L172","article-title":"Cellular response of antioxidant metalloproteins in Cu\/Zn SOD transgenic mice exposed to hyperoxia","volume":"281","author":"Levy","year":"2001","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41401-020-0396-4","article-title":"Zinc as a countermeasure for cadmium toxicity","volume":"42","author":"Yu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/00006676-200104000-00012","article-title":"Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis","volume":"22","author":"Quilliot","year":"2001","journal-title":"Pancreas"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Hajhashemy, Z., Foshati, S., Bagherniya, M., and Askari, G. (2025). The association between blood selenium and metabolic syndrome in adults: A systematic review and dose\u2013response meta-analysis of epidemiologic studies. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1451342"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.5551\/jat.RV17057","article-title":"The role of zinc homeostasis in the prevention of diabetes mellitus and cardiovascular diseases","volume":"28","author":"Tamura","year":"2021","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/507441a","article-title":"The zinc link","volume":"507","author":"Kraus","year":"2014","journal-title":"Nature"},{"key":"ref_95","first-page":"699","article-title":"Zinc and enzymes in the synovial fluid and blood in various types of rheumatism","volume":"45","author":"Buneaux","year":"1978","journal-title":"Rev. Rhum. Mal. Osteoartic."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1385\/BTER:106:2:123","article-title":"Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis","volume":"106","author":"Yazar","year":"2005","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Sorenson, J.R.J. (1987). Synovial Fluid Copper, Zinc and Selenium in Relation to Inflammatory Parameters in Rheumatic Diseases. Biology of Copper Complexes, Humana Press.","DOI":"10.1007\/978-1-4612-4584-1"},{"key":"ref_98","first-page":"247","article-title":"Factors influencing the absorption of trace elements in healthy conditions and in gastrointestinal diseases","volume":"26","author":"Struniolo","year":"1994","journal-title":"Ital. J. Gastroenterol."},{"key":"ref_99","unstructured":"Said, H.M. (2018). Chapter 61\u2014Trace Metal Absorption and Transport. Physiology of the Gastrointestinal Tract, Academic Press. [6th ed.]."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1111\/1750-3841.14785","article-title":"Bioavailability Assessment of Copper, Iron, Manganese, Molybdenum, Selenium, and Zinc from Selenium-Enriched Lettuce","volume":"84","author":"Cadore","year":"2019","journal-title":"J. Food Sci."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Pattan, V., Chang Villacreses, M.M., Karnchanasorn, R., Chiu, K.C., and Samoa, R. (2021). Daily Intake and Serum Levels of Copper, Selenium and Zinc According to Glucose Metabolism: Cross-Sectional and Comparative Study. Nutrients, 13.","DOI":"10.3390\/nu13114044"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/13\/2069\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:56:25Z","timestamp":1760032585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/13\/2069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,21]]},"references-count":101,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["nu17132069"],"URL":"https:\/\/doi.org\/10.3390\/nu17132069","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,21]]}}}