{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:15:52Z","timestamp":1766056552407,"version":"3.48.0"},"reference-count":39,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2023\/07\/X\/NZ5\/00123"],"award-info":[{"award-number":["2023\/07\/X\/NZ5\/00123"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Metropolis GZM, granted within Area 2\u2014Support for Research of the Metropolitan Science and Education Support Fund","award":["RW\/30\/2025"],"award-info":[{"award-number":["RW\/30\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Proteoglycans and their fragments have potential as diagnostic or theragnostic biomarkers to identify diseases characterized by dysregulated extracellular matrix remodeling, such as juvenile idiopathic arthritis (JIA). Therefore, our study aimed to evaluate the diagnostic utility of plasma proteoglycan profiles, namely, aggrecan, decorin, and biglycan, released from osteoarticular structures into the blood of children with juvenile idiopathic arthritis. These profiles are potential biomarkers of tissue destruction and\/or indicators of the efficacy of therapy with the biologic agent etanercept (ETA). This study was conducted on 263 blood samples collected from 25 healthy children and 34 children at various stages of juvenile idiopathic arthritis disease: immediately after diagnosis, following treatment with disease-modifying antirheumatic drugs (DMARD) (methotrexate, sulfasalazine, and prednisone), and during 3, 6, 12, 18, and 24 months of therapy with etanercept. Quantitative levels of aggrecan, biglycan, and decorin were measured using ELISA kits. In children with JIA, plasma aggrecan levels were elevated at diagnosis, decreased after ineffective DMARD therapy, and increased again at 24 months of etanercept treatment despite clinical improvement. By contrast, biglycan levels were similar to those in healthy controls but decreased during etanercept therapy. Decorin levels were initially high in untreated and DMARD-treated patients but returned to normal after 24 months of biologic treatment. After considering these findings and the ROC analysis, we conclude that decorin appears to be a promising biomarker for diagnosing and monitoring etanercept therapy in JIA, and biglycan is a useful biochemical marker for assessing the effectiveness of ETA treatment.<\/jats:p>","DOI":"10.3390\/ijms262412168","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:08:28Z","timestamp":1766056108000},"page":"12168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Aggrecan, Biglycan, and Decorin as Biomarkers of Osteoarticular Alterations in Juvenile Idiopathic Arthritis\u2014A Preliminary Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-4841","authenticated-orcid":false,"given":"Kornelia","family":"Ku\u017anik-Trocha","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3574-4133","authenticated-orcid":false,"given":"Katarzyna","family":"Winsz-Szczotka","sequence":"additional","affiliation":[{"name":"Department of Practical Laboratory Medicine, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-2628","authenticated-orcid":false,"given":"Krystyna","family":"Olczyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Gruenpeter","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The John Paul II Pediatric Center in Sosnowiec, ul. G. Zapolskiej 3, 41-218 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-5884","authenticated-orcid":false,"given":"Katarzyna","family":"Komosi\u0144ska-Vassev","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Strokotova, A.V., and Grigorieva, E.V. (2022). Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415678"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"C754","DOI":"10.1152\/ajpcell.00442.2021","article-title":"Proteoglycans and proteoglycan mimetics for tissue engineering","volume":"322","author":"Nguyen","year":"2022","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.matbio.2015.02.003","article-title":"Proteoglycan form and function: A comprehensive nomenclature of proteoglycans","volume":"42","author":"Iozzo","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1369\/0022155412464638","article-title":"An introduction to proteoglycans and their localization","volume":"60","author":"Couchman","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/BOR.0000000000000845","article-title":"Blood and urine biomarkers in osteoarthritis\u2014An update on cartilage associated type II collagen and aggrecan markers","volume":"34","author":"Mobasheri","year":"2022","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41419-022-04919-1","article-title":"Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity","volume":"13","author":"Krawetz","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yamashita, R., Tsutsui, S., Mizumoto, S., Watanabe, T., Yamamoto, N., Nakano, K., Yamada, S., Okamura, T., and Furuichi, T. (2025). CANT1 Is Involved in Collagen Fibrogenesis in Tendons by Regulating the Synthesis of Dermatan\/Chondroitin Sulfate Attached to the Decorin Core Protein. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062463"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alcaide-Ruggiero, L., Cugat, R., and Dom\u00ednguez, J.M. (2023). Proteoglycans in Articular Cartilage and Their Contribution to Chondral Injury and Repair Mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310824"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.22203\/eCM.v012a11","article-title":"The structure and function of cartilage proteoglycans","volume":"12","author":"Roughley","year":"2006","journal-title":"Eur. Cell Mater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s12079-021-00616-4","article-title":"Sequence features, structure, ligand interaction, and diseases in small leucine rich repeat proteoglycans","volume":"15","author":"Matsushima","year":"2021","journal-title":"J. Cell Commun. Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e70011","DOI":"10.1002\/pgr2.70011","article-title":"Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling","volume":"2","author":"Kemberi","year":"2024","journal-title":"Proteoglycan Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.clinbiochem.2014.01.027","article-title":"Influence of proteolytic-antiproteolytic enzymes and prooxidative-antioxidative factors on proteoglycan alterations in children with juvenile idiopathic arthritis","volume":"47","author":"Gruenpeter","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Garner, A.J., Saatchi, R., Ward, O., and Hawley, D.P. (2021). Juvenile Idiopathic Arthritis: A Review of Novel Diagnostic and Monitoring Technologies. Healthcare, 9.","DOI":"10.3390\/healthcare9121683"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12969-021-00629-8","article-title":"Juvenile idiopathic arthritis: From aetiopathogenesis to therapeutic approaches","volume":"19","author":"Zaripova","year":"2021","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.3390\/jcm11072013","article-title":"The Effects of TNF-\u03b1 Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-\u03b21 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis","volume":"11","author":"Wojdas","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.pedneo.2015.09.010","article-title":"Potential Effects of Interleukins on the Pathogenesis of Systemic Onset Juvenile Idiopathic Arthritis","volume":"57","author":"Xu","year":"2016","journal-title":"Pediatr. Neonatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.5606\/ArchRheumatol.2017.6067","article-title":"Interleukin-17A Levels Increase in Serum of Children with Juvenile Idiopathic Arthritis","volume":"32","author":"Doronjski","year":"2017","journal-title":"Arch. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wojdas, M., D\u0105bkowska, K., and Winsz-Szczotka, K. (2021). Alterations of extracellular matrix components in the course of juvenile idiopathic arthritis. Metabolites, 11.","DOI":"10.3390\/metabo11030132"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10067-014-2571-9","article-title":"Reactive oxygen species and serum antioxidant defense in juvenile idiopathic arthritis","volume":"34","author":"Sarniak","year":"2015","journal-title":"Clin. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"355","DOI":"10.55563\/clinexprheumatol\/ck090i","article-title":"Juvenile idiopathic arthritis patients have a distinct cartilage and bone biomarker profile that differs from healthy and knee-injured children","volume":"38","author":"Struglics","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2437239","DOI":"10.1080\/08916934.2024.2437239","article-title":"Identification and validation of susceptibility modules and hub genes in polyarticular juvenile idiopathic arthritis using WGCNA and machine learning","volume":"58","author":"Liu","year":"2025","journal-title":"Autoimmunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.bbrc.2015.02.018","article-title":"Plasma and urinary glycosaminoglycans in the course of juvenile idiopathic arthritis","volume":"458","author":"Wisowski","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","first-page":"291","article-title":"Circulating keratan sulfate as a marker of metabolic changes of cartilage proteoglycan in juvenile idiopathic arthritis; Influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations","volume":"53","author":"Siwiec","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.joca.2021.03.019","article-title":"Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis","volume":"29","author":"Han","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"808","DOI":"10.3892\/etm.2021.10240","article-title":"Blocking TNF\u03b1 attenuates progressive cartilage matrix degradation in inflammatory arthritis","volume":"22","author":"Park","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3892\/mmr.2022.12615","article-title":"Cartilage tissue engineering: From proinflammatory and anti-inflammatory cytokines to osteoarthritis treatments (Review)","volume":"25","author":"Liu","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Varela-Eirin, M., D\u00edaz-Flores, L., Gonz\u00e1lez-Garc\u00eda, C., and Fonseca, E. (2024). Chondrocytes revisited: Functional heterogeneity, plasticity, and their role in cartilage repair. Biomedicines, 12.","DOI":"10.3390\/biomedicines12020258"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.matbio.2010.10.007","article-title":"MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein","volume":"30","author":"Durigova","year":"2011","journal-title":"Matrix Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e004317","DOI":"10.1136\/rmdopen-2024-004317","article-title":"Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: A population-based study of the Nordic JIA cohort","volume":"10","author":"Glerup","year":"2024","journal-title":"RMD Open"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1440-1827.2010.02547.x","article-title":"Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases","volume":"60","author":"Shiomi","year":"2010","journal-title":"Pathol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/ar630","article-title":"Aggrecanases and cartilage matrix degradation","volume":"5","author":"Nagase","year":"2003","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2018.08.038","article-title":"Reactive oxygen species, aging and articular cartilage homeostasis","volume":"132","author":"Bolduc","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Maouche, A., Boumediene, K., and Baug\u00e9, C. (2024). Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111656"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"He, F., Wu, H., He, B., Han, Z., Chen, J., and Huang, L. (2024). Antioxidant hydrogels for the treatment of osteoarthritis: Mechanisms and recent advances. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1488036"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Nini\u0107, A., Rajkov, B., Kotur-Stevuljevi\u0107, J., Erceg, S., Sopi\u0107, M., Munjas, J., Spasojevi\u0107-Kalimanovska, V., Mitrovi\u0107, M., Memon, L., and Gardijan, V. (2025). Association Between Redox and Inflammatory Biomarkers with the Presence and Severity of Obstructive Sleep Apnea. Medicina, 61.","DOI":"10.3390\/medicina61091557"},{"key":"ref_36","first-page":"390","article-title":"International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: Second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12969-016-0085-5","article-title":"Clinical outcome measures in juvenile idiopathic arthritis","volume":"14","author":"Consolaro","year":"2016","journal-title":"Pediatr. Rheumatol. Online J."},{"key":"ref_38","unstructured":"(2015, July 14). Treatment of Active Rheumatoid Arthritis and Juvenile Idiopathic Arthritis\u2014Drug Program\u2014Appendix B.33, Ministry of Health, November 2014, (In Polish)."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/acr.24853","article-title":"American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis","volume":"74","author":"Onel","year":"2022","journal-title":"Arthritis Care Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:10:08Z","timestamp":1766056208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":39,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412168"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412168","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}