ArticleInternational journal of molecular sciences2018
A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Axial spondyloarthritis, psoriatic arthritis and systemic lupus erythematosus share common molecular features based on post-hoc analysis of serum biomarkers.Rheumatology international · 2025Trial
- Cartilage tissue turnover increases with high- compared to low-intensity resistance training in patients with knee OA.Arthritis research & therapy · 2023Trial
- A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology · 2021Trial
- Osteoarthritis: Epidemiology, Diagnosis, and Treatment.MedComm · 2026Review
- Therapeutic subtypes of knee osteoarthritis: differential treatment effects among predicted endotypes in past clinical trials.Arthritis research & therapy · 2026Article
- Inhibition of CDK8 rescues impaired ischemic fracture healing.NPJ Regenerative medicine · 2026Article
- Gold Nanoparticles as a Tool to Detect Biomarkers in Osteoarthritis: New Insights.Indian journal of microbiology · 2025Article
- Observation of the Effects of Infrapatellar Fat Pad Excision on the Inflammatory Progression of Knee Osteoarthritis in Mice.Journal of inflammation research · 2025Article
- Association of biochemical markers with bone marrow lesion changes on imaging-data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.Arthritis research & therapy · 2024Article
- Extracellular matrix turnover biomarkers reflect pharmacodynamic effects and treatment response of adalimumab in patients with axial spondyloarthritis-results from two randomized controlled trials.Arthritis research & therapy · 2023Article
- Cartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics.International journal of molecular sciences · 2023Review
- A Highly Sensitive Biomarker of Type II Collagen C-Terminal Pro-Peptide Associated with Cartilage Formation.International journal of molecular sciences · 2022Article
- Clinical monitoring in osteoarthritis: Biomarkers.Osteoarthritis and cartilage · 2022Article
- Extracellular matrix protein turnover markers are associated with axial spondyloarthritis-a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain.Arthritis research & therapy · 2022Article
- Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.Current opinion in rheumatology · 2022Review
- Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis.Frontiers in genetics · 2022Article
- A biomarker perspective on the acute effect of exercise with and without impact on joint tissue turnover: an exploratory randomized cross-over study.European journal of applied physiology · 2021Article
- Concerted Actions by PIICP, CTXII, and TNF-α in Patients with Juvenile Idiopathic Arthritis.Biomolecules · 2021Article
- Biological strategies for osteoarthritis: from early diagnosis to treatment.International orthopaedics · 2021Review
- COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration.Frontiers in genetics · 2021Article
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utility of PIIBNP as a marker in preclinical and clinical settings has not been fully investigated yet. In this study, we aimed to characterize an antibody targeting human PIIBNP and to develop an immunoassay assessing type II collagen synthesis in human blood samples. A high sensitivity electrochemiluminescence immunoassay, hsPRO-C2, was developed using a well-characterized antibody against human PIIBNP. Human cartilage explants from replaced osteoarthritis knees were cultured for ten weeks in the presence of growth factors, insulin-like growth factor 1 (IGF-1) or recombinant human fibroblast growth factor 18 (rhFGF-18). The culture medium was changed every seven days, and levels of PIIBNP, PIIANP, and matrix metalloproteinase 9-mediated degradation of type II collagen (C2M) were analyzed herein. Serum samples from a cross-sectional knee osteoarthritis cohort, as well as pediatric and rheumatoid arthritis samples, were assayed for PIIBNP and PIIANP. Western blot showed that the antibody recognized PIIBNP either as a free fragment or attached to the main molecule. Immunohistochemistry demonstrated that PIIBNP was predominately located in the extracellular matrix of the superficial and deep zones and chondrocytes in both normal and osteoarthritic articular cartilage. In addition, the hsPRO-C2 immunoassay exhibits acceptable technical performances. In the human cartilage explants model, levels of PIIBNP, but not PIIANP and C2M, were increased (2 to 7-fold) time-dependently in response to IGF-1. Moreover, there was no significant correlation between PIIBNP and PIIANP levels when measured in knee osteoarthritis, rheumatoid arthritis, and pediatric serum samples. Serum PIIBNP was significantly higher in controls (KL0/1) compared to OA groups (KL2/3/4,
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