Plasma proteomics identifies CRTAC1 as a biomarker for osteoarthritis severity and progression
Open accessAbstract
Objectives: The aim of this study was to identify biomarkers for radiographic OA severity and progression acting within the inflammation and metabolic pathways. Methods: For 3517 Rotterdam Study participants, 184 plasma protein levels were measured using Olink inflammation and cardiometabolic panels. We studied associations with severity and progression of knee, hip and hand OA and a composite overall OA burden score by multivariable regression models, adjusting for age, sex, cell counts and BMI. Results: We found 18 significantly associated proteins for overall OA burden, of which 5 stayed significant after multiple testing correction: circulating cartilage acidic protein 1 (CRTAC1), cartilage oligomeric matrix protein (COMP), thrombospondin 4, IL-18 receptor 1 (IL-18R1) and TNF ligand superfamily member 14. These proteins were also associated with progression of knee OA, with the exception of IL-18R1. The strongest association was found for the level of CRTAC1, with 1 s.d. increase in protein level resulting in an increase of 0.09 (95% CI 0.06, 0.12) in the overall OA Kellgren–Lawrence sum score (P = 2.9 × 10−8) in the model adjusted for age, sex, BMI and cell counts. This association was also present with the severity of OA in all three joints and progression of knee OA and was independent of BMI. We observed a stronger association for CRTAC1 with OA than for the well-known OA biomarker COMP. Conclusion: We identified several compelling biomarkers reflecting the overall OA burden and the increased risk for OA progression. CRTAC1 was the most compelling and robust biomarker for OA severity and progression. Such a biomarker may be used for disease monitoring.
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CTX-II is elevated in urine of knee OA patients.
“and is elevated in urine of knee OA patients”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [24]
The Introduction states that urinary CTX-II levels are associated with OA prevalence and progression at the population level. It does not specify knee OA or state that urinary CTX-II is elevated in knee OA patients relative to a comparison group. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCTX-II correlates with MRI-detected structural abnormalities: osteophytes R = 0.330, bone marrow lesions R = 0.252, and cartilage degradation R = 0.218, p < 0.05.
“and MRI-detected structural abnormalities (osteophytes R = 0.330, bone marrow lesions R = 0.252, cartilage degradation R = 0.218, p < 0.05)”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [24]
The Introduction (page unavailable) says urinary CTX-II is associated with osteoarthritis prevalence and progression at the population level. It does not report the claimed MRI correlations or their R and p values. The Methods describe radiographic, rather than MRI, measurements. (LLM, conf=0.82)
Experimental — accuracy not yet measuredCTX-II is a fragment of type II collagen, which constitutes 90% of cartilage collagen, and is cleaved by collagenases.
“Specifically, CTX-II is a fragment of type II collagen (90% of cartilage collagen) cleaved by collagenases”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [24]
The Introduction mentions urinary CTX-II as an osteoarthritis biomarker, but does not define it as a type II collagen fragment or give the 90% figure. The Discussion mentions collagenases in relation to MMP-10, not CTX-II. Searches for CTX-II cleavage and cartilage collagen composition found no passage addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredCTX-II correlates with disease severity, being higher in Kellgren-Lawrence grades 3-4 than grade 2.
“correlating with disease severity (higher in Kellgren-Lawrence grades 3–4 vs. 2)”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [24]
The Introduction says urine CTX-II is associated with osteoarthritis prevalence and progression, but does not address its relationship with disease severity. The Methods and Results use Kellgren–Lawrence scores to assess severity for other proteins; they do not report CTX-II levels in grades 3–4 versus grade 2 (searched: CTX-II and the grade comparison). (LLM, conf=0.76)
Experimental — accuracy not yet measuredMultivariate analysis highlights osteophyte load and synovitis as predictors of CTX-II, suggesting contributions from bone and synovium.
“with multivariate analysis highlighting osteophyte load and synovitis as predictors, suggesting contributions from bone and synovium [23,24,25].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [24]
The Results (Knee OA) link osteophyte formation to CRTAC1 levels, not CTX-II. The Discussion states that uCTX-II data were unavailable, so the paper could not assess the claimed CTX-II predictors; the Introduction mentions synovial inflammation only as a general feature of osteoarthritis. No page numbers are provided in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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- Authors
- Szilagyi, I. A., Vallerga, C. L., Boer, C. G., Schiphof, D., Ikram, M. A., Bierma-Zeinstra, S. M. A., & van Meurs, J. B. J.
- Affiliations
- Department of General Practice
- Department of Internal Medicine
- Erasmus MC (NL)
- Venue
- Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-08-04
- Volume
- 62
- Issue
- 3
- Pages
- 1286-1295
- ISSN
- 1462-0324 (ISSN-L)
- 1462-0332
- PMC
- PMC9977119
- OpenAlex
- W4289844876
- Cited by
- 51
- References
- 44
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 14 · 2023: 12 · 2022: 2
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Lara D. Veeken (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, cc-by-nc)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by-nc)
- Funders
- Netherlands Organisation for Health Research and Development (849200003)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Hip disorders and treatments
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoarthritis, CRTAC1, plasma biomarkers, disease progression, disease severity, knee osteoarthritis, hip osteoarthritis, hand osteoarthritis, cartilage oligomeric matrix protein, thrombospondin-4, Kellgren-Lawrence grade, inflammation
- MeSH terms
- Calcium-Binding Proteins, Humans, Inflammation, Knee Joint, Biomarkers, Disease Progression, Osteoarthritis, Knee, Proteomics, Cartilage Oligomeric Matrix Protein
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