{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T22:08:19Z","timestamp":1780092499346,"version":"3.54.0"},"reference-count":19,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Fund Denmark","award":["0153-00086B"],"award-info":[{"award-number":["0153-00086B"]}]},{"name":"Danish Research Foundation","award":["0153-00086B"],"award-info":[{"award-number":["0153-00086B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The type II collagen C-terminal pro-peptide is one of the most abundant polypeptides in cartilage. The purpose of this study was to develop a competitive chemiluminescence enzyme-linked immunosorbent assay, CALC2, targeting this pro-peptide as a marker of cartilage formation. Technical assay parameters were evaluated. CALC2 level was measured after in vitro cleavage of recombinant type II collagen with bone morphogenetic protein-1 (BMP-1) and treatment of ex vivo human osteoarthritis (OA) cartilage explant model (HEX) with insulin-like growth factor-1 (IGF-1). Serum CALC2 levels were assessed in 18 patients with rheumatoid arthritis (RA), 19 patients with ankylosing spondylitis (AS), and 18 age- and sex-matched controls in cohort 1 and 8 patients with OA and 14 age- and sex-matched controls in cohort 2. Type II collagen cleavage with BMP-1 increased the CALC2 level. IGF-1 treatment increased the CALC2 levels in HEX compared with the untreated explants (p &lt; 0.05). Results were confirmed using Western blot analysis. CALC2 levels were decreased in the patients with RA and AS compared with the healthy controls (p = 0.01 and p = 0.02, respectively). These findings indicate that CALC2 may be a novel biomarker of type II collagen formation. However, further preclinical and clinical studies are required to validate these findings.<\/jats:p>","DOI":"10.3390\/ijms24010454","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:42:48Z","timestamp":1672206168000},"page":"454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Highly Sensitive Biomarker of Type II Collagen C-Terminal Pro-Peptide Associated with Cartilage Formation"],"prefix":"10.3390","volume":"24","author":[{"given":"Helena","family":"Port","sequence":"first","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, 2200 K\u00f8benhavn, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7952-9297","authenticated-orcid":false,"given":"Anne-Christine","family":"Bay-Jensen","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten A.","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorbj\u00f8rn","family":"Gantzel","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery Unit, Gentofte University Hospital, 2820 Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0202-1417","authenticated-orcid":false,"given":"Christian S.","family":"Thudium","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4612-1014","authenticated-orcid":false,"given":"Signe","family":"Holm Nielsen","sequence":"additional","affiliation":[{"name":"Biomarkers and Research, Nordic Bioscience, 2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: Structure, composition, and function","volume":"1","author":"Bedi","year":"2009","journal-title":"Sports Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18789","DOI":"10.3390\/ijms151018789","article-title":"Cartilage turnover reflected by metabolic processing of type II collagen: A novel marker of anabolic function in chondrocytes","volume":"15","author":"Gudmann","year":"2014","journal-title":"Int. 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