{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:26:21Z","timestamp":1793741181190,"version":"4.6.1"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007771","name":"\u015al\u0105ski Uniwersytet Medyczny","doi-asserted-by":"publisher","award":["grant number PCN-1-020\/N\/0\/I from the Medical University of Silesia in Katowice, Po-land."],"award-info":[{"award-number":["grant number PCN-1-020\/N\/0\/I from the Medical University of Silesia in Katowice, Po-land."]}],"id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Joint destruction in juvenile idiopathic arthritis (JIA), initiated in the early, preclinical stage of the disease, is diagnosed on the basis of clinical evaluation and radiographic imaging. The determination of circulating cartilage-matrix turnover markers can facilitate the diagnosis and application of better and earlier treatment strategies for JIA. We have shown that 96 JIA patients have elevated levels of procollagen II C-terminal propeptide (PIICP), reflecting the extent of joint cartilage biosynthesis, and C-telopeptide of type II collagen (CTXII), a biomarker of the resorption of this tissue. Patients who did not respond to treatment had particularly high levels of these markers. JIA treatment resulted in the normalization of these markers in remissive patients, but not in those with active JIA. We showed correlations between examined variables and inflammatory process indicators, i.e., C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and tumor necrosis factor-\u03b1 (TNF-\u03b1). The TNF-\u03b1 of patients responding to treatment correlated with PIICP, especially in the patients before treatment (r = 0.898, p &lt; 0.001). Significant changes in serum PIICP during JIA therapy suggest its potential diagnostic utility in the monitoring of disease activity and the possibility of its use in assessing treatment towards remission. Understanding changes in type II collagen metabolism over the course of the discussed arthritis may allow the implementation of both new diagnostic tools and new therapeutic strategies in children with JIA.<\/jats:p>","DOI":"10.3390\/biom11050648","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T10:41:58Z","timestamp":1619606518000},"page":"648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Concerted Actions by PIICP, CTXII, and TNF-\u03b1 in Patients with Juvenile Idiopathic Arthritis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3574-4133","authenticated-orcid":false,"given":"Katarzyna","family":"Winsz-Szczotka","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, ul. Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-4841","authenticated-orcid":false,"given":"Kornelia","family":"Ku\u017anik-Trocha","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, ul. Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Lach\u00f3r-Motyka","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The John Paul II Pediatric Center in Sosnowiec, ul. Gabrieli Zapolskiej 3, 41-218 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Lemski","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, ul. Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, ul. Jedno\u015bci 8, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3899\/jrheum.180168","article-title":"Pediatric Rheumatology International Trials Organization (PRINTO). Toward new classification criteria for juvenile idiopathic arthritis: First steps, Pediatric Rheumatology International Trials Organization International Consensus","volume":"46","author":"Martini","year":"2019","journal-title":"J. Rheumatol."},{"key":"ref_2","first-page":"819","article-title":"Treating juvenile idiopathic arthritis to target: Recommendations of an international task force","volume":"77","author":"Ravelli","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4274\/balkanmedj.2017.0111","article-title":"Juvenile idiopathic arthritis","volume":"34","author":"Barut","year":"2017","journal-title":"Balk. Med. J."},{"key":"ref_4","first-page":"5","article-title":"Connective tissue metabolism in patients with juvenile idiopathic arthritis: 10-year follow-up study","volume":"6","author":"Shevchenko","year":"2019","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1111\/1756-185X.13584","article-title":"Ultrasound detected changes in joint cartilage thickness in juvenile idiopathic arthritis","volume":"22","author":"Mitra","year":"2019","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1080\/03009742.2016.1192681","article-title":"Circulating cartilage oligomeric matrix protein in juvenile idiopathic arthritis","volume":"46","author":"Lewander","year":"2017","journal-title":"Scand. J. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1111\/febs.14818","article-title":"The extracellular matrix as a multitasking player in disease","volume":"286","author":"Theocharis","year":"2019","journal-title":"FEBS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1007\/s13238-017-0377-7","article-title":"The minor collagens in articular cartilage","volume":"8","author":"Luo","year":"2017","journal-title":"Protein Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1089\/adt.2012.474","article-title":"Extracellular matrix remodeling: The common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure","volume":"11","author":"Karsdal","year":"2013","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5604\/17322693.1196355","article-title":"Metabolism of glycosaminoglycans in the course of juvenile idiopathic arthritis","volume":"70","author":"Mencner","year":"2016","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.cca.2005.09.020","article-title":"Collagen markers in early arthritic diseases","volume":"365","author":"Elsaid","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_12","first-page":"3050","article-title":"GPDPLQ(1237)-a type II collagen neo-epitope biomarker of osteoclast- and inflammation-derived cartilage degradation in vitro","volume":"28","author":"Katri","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Luo, Y., He, Y., Reker, D., Gudmann, N.S., Henriksen, K., Simonsen, O., Ladel, C., Michaelis, M., Mobasheri, A., and Karsdal, M. (2018). A novel high sensitivity type II collagen blood-based biomarker, PRO-C2, for assessment of cartilage formation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113485"},{"key":"ref_14","first-page":"799","article-title":"Serum TNF-\u03b1 levels and indicators of disease activity in children with oligoarticular juvenile idiopathic arthritis (oJIA) in the first year of the disease","volume":"60","author":"Adamczak","year":"2014","journal-title":"Clin. Lab."},{"key":"ref_15","first-page":"390","article-title":"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_16","doi-asserted-by":"crossref","unstructured":"Winsz-Szczotka, K., Ku\u017anik-Trocha, K., Gruenpeter, A., Wojdas, M., D\u0105bkowska, K., and Olczyk, K. (2020). Association of circulating COMP and YKL-40 as markers of metabolic changes of cartilage with adipocytokines in juvenile idiopathic arthritis. Metabolites, 10.","DOI":"10.3390\/metabo10020061"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jhep.2015.08.014","article-title":"Collagen and tissue turnover as a function of age: Implications for fibrosis","volume":"64","author":"Karsdal","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_18","first-page":"310","article-title":"Effects of etanercept on serum biochemical markers of cartilage metabolism in patients with spondyloarthropathy","volume":"35","author":"Briot","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.17219\/acem\/68362","article-title":"Fibulin-3 and other cartilage metabolism biomarkers in relationship to calprotectin (MRP8\/14) and disease activity in rheumatoid arthritis patients treated with anti-TNF therapy","volume":"27","author":"Kucharz","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1136\/ard.62.1.27","article-title":"Procollagen II C propeptide level in the synovial fluid as a predictor of radiographic progression in early knee osteoarthritis","volume":"62","author":"Sugiyama","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.3892\/etm.2016.3480","article-title":"Evaluation of the effect of N-acetyl-glucosamine administration on biomarkers for cartilage metabolism in healthy individuals without symptoms of arthritis: A randomized double-blind placebo-controlled clinical study","volume":"12","author":"Tomonaga","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1002\/art.11331","article-title":"Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: Relationship to mediators of systemic and local inflammation","volume":"48","author":"Fraser","year":"2003","journal-title":"Arthritis Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1172\/JCI117753","article-title":"Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of diseaseidentified by serum markers of cartilage metabolism","volume":"95","author":"Carey","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_24","first-page":"1765","article-title":"Procollagen II C-propeptide in joint fluid: Changes in concentration with age, time after knee injury, and osteoarthritis","volume":"23","author":"Lohmander","year":"1996","journal-title":"J. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"ii78","DOI":"10.1136\/ard.61.suppl_2.ii78","article-title":"Type II collagen degradation and its regulation in articular cartilage in osteoarthritis","volume":"61","author":"Poole","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1136\/ard.2005.039032","article-title":"Assessment of the clinical significance of gelatinase activity in patients with juvenile idiopathic arthritis using quantitative protein substrate zymography","volume":"65","author":"Peake","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.joca.2017.04.001","article-title":"Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain","volume":"25","author":"Leung","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_28","first-page":"991","article-title":"French Section on Osteoarthritis. MRI and serum biomarkers correlate with radiographic features in painful hand osteoarthritis","volume":"34","author":"Roux","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R229","DOI":"10.1186\/ar3216","article-title":"Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254)","volume":"12","author":"Catterall","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00296-018-3988-2","article-title":"Cartilage turnover and intra-articular corticosteroid injections in knee osteoarthritis","volume":"38","author":"Klocke","year":"2018","journal-title":"Rheumatol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13075-016-0976-3","article-title":"Association between biomarkers of tissue inflammation and progression of osteoarthritis: Evidence from the Rotterdam study cohort","volume":"18","author":"Siebuhr","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"743","DOI":"10.5604\/17322693.1208887","article-title":"Macrophages-silent enemies in juvenile idiopathic arthritis","volume":"70","author":"Orczyk","year":"2016","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/phar.1938","article-title":"Cytokine biomarkers of disease activity and therapeutic response after initiating methotrexate therapy in patients with juvenile idiopathic arthritis","volume":"37","author":"Funk","year":"2017","journal-title":"Pharmacotherapy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.joca.2005.10.004","article-title":"Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts","volume":"14","author":"Honorati","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.4049\/jimmunol.171.7.3855","article-title":"Antagonistic effects of TNF-alpha on TGF-beta signaling through down-regulation of TGF-beta receptor type II in human dermal fibroblasts","volume":"171","author":"Yamane","year":"2003","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/j.1440-1681.2007.04868.x","article-title":"Implications of cross-talk between tumour necrosis factor and insulin-like growth factor-1 signalling in skeletal muscle","volume":"35","author":"Grounds","year":"2008","journal-title":"Clin. Exp. Pharm. Physiol."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/rheumatology\/41.6.691","article-title":"Serum and synovial fluid concentration of vascular endothelial growth factor in juvenile idiopathic arthritides","volume":"41","author":"Vignola","year":"2002","journal-title":"Rheumatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3856897","DOI":"10.1155\/2018\/3856897","article-title":"Low serum IGF-1 in boys with recent onset of juvenile idiopathic arthritis","volume":"2018","author":"Lundell","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000228902","article-title":"IGF-I and IGF-binding proteins in articular exudates of children with post-traumatic knee damage and juvenile idiopathic arthritis","volume":"76","author":"Guszczyn","year":"2009","journal-title":"Pathobiology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbapap.2011.06.020","article-title":"Proteases involved in cartilage matrix degradation in osteoarthritis","volume":"1824","author":"Troeberg","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Araki, Y., and Mimura, T. (2017). Matrix metalloproteinase gene activation resulting from disordred epigenetic mechanisms in rheumatoid arthritis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050905"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.02.005","article-title":"Biochemical and biological attributes of matrix metalloproteinases","volume":"147","author":"Cui","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_45","first-page":"224","article-title":"Matrix metalloproteinase interactions with collagen and elastin","volume":"44\u201346","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8785","DOI":"10.1074\/jbc.R113.451211","article-title":"Interstitial collagen catabolism","volume":"288","author":"Fields","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.3899\/jrheum.110352","article-title":"Levels of serum matrix metalloproteinase-3 correlate with disease activity in the enthesitis-related arthritis category of juvenile idiopathic arthritis","volume":"38","author":"Viswanath","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7420345","DOI":"10.1155\/2019\/7420345","article-title":"Levels of selected matrix metalloproteinases, their inhibitors in saliva, and oral status in juvenile idiopathic arthritis patients vs. healthy controls","volume":"2019","author":"Kobus","year":"2019","journal-title":"BioMed. Res. Int."},{"key":"ref_49","first-page":"36","article-title":"Indices of matrix metalloproteinases (MMP-2, MMP-9, TIMP-1) with juvenile arthritis in children","volume":"7","author":"Ogorodova","year":"2013","journal-title":"Annals Russ. Acad. Med. Sci."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"5601593","DOI":"10.1155\/2017\/5601593","article-title":"ROS: Crucial intermediators in the pathogenesis of intervertebral disc degeneration","volume":"2017","author":"Feng","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.imlet.2015.03.006","article-title":"Anti-type II collagen antibodies detection and avidity in patients with oligoarticular and polyarticular forms of juvenile idiopathic arthritis","volume":"165","author":"Araujo","year":"2015","journal-title":"Immunol. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1546-0096-12-22","article-title":"Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)","volume":"12","author":"Berntson","year":"2014","journal-title":"Pediatr. Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1002\/acr.22911","article-title":"Quantifying temporomandibular joint synovitis in children with juvenile idiopathic arthritis","volume":"68","author":"Resnick","year":"2016","journal-title":"Arthritis Care Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Sambataro, S., Cervino, G., Bocchieri, S., La Bruna, R., and Cicci\u00f9, M. (2019). TMJ dysfunctions systemic implications and postural assessments: A review of recent literature. J. Funct. Morphol. Kinesiol., 4.","DOI":"10.3390\/jfmk4030058"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/5\/648\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:54:33Z","timestamp":1760162073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/5\/648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,28]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["biom11050648"],"URL":"https:\/\/doi.org\/10.3390\/biom11050648","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,28]]}}}