A Highly Sensitive Biomarker of Type II Collagen C-Terminal Pro-Peptide Associated with Cartilage Formation

Helena Port*, Anne-Christine Bay-Jensen, Yi He, Morten A Karsdal, Thorbjørn Gantzel, Christian S Thudium, Signe Holm Nielsen

*Corresponding author for this work


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 < 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.

Original languageEnglish
Article number454
JournalInternational Journal of Molecular Sciences
Issue number1
Publication statusPublished - Jan 2023


  • Humans
  • Collagen Type II
  • Insulin-Like Growth Factor I/therapeutic use
  • Cartilage
  • Arthritis, Rheumatoid
  • Peptides/therapeutic use
  • Osteoarthritis
  • Spondylitis, Ankylosing/drug therapy
  • Biomarkers
  • Cartilage, Articular


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