Cartilage Acidic Protein 1 in Plasma Associates With Prevalent Osteoarthritis and Predicts Future Risk as Well as Progression to Joint Replacements: Results From the UK Biobank Resource

Abstract

Objective. The level of cartilage acidic protein 1 (CRTAC1) in plasma was recently discovered to be associated with osteoarthritis (OA) risk and progression to joint replacement in Iceland. This study was undertaken to validate these findings in an independent population.Methods. In this study, 1,462 plasma proteins were measured in 54,265 participants from the UK Biobank on the Olink Explore platform. We analyzed the association of plasma proteins with prevalent OA, incident OA, and progression to joint replacement. We assessed the specificity of OA association through comparison of associations with inflammatory joint diseases and with previous joint replacement.Results. The CRTAC1 protein showed the strongest association with prevalent knee OA (odds ratio [OR] 1.34 [95% confidence interval (95% CI) 1.27, 1.41]) and was associated with hip OA (OR 1.19 [95% CI 1.11, 1.28]). It predicted incident diagnosis of OA in the knee (hazard ratio [HR] 1.40 [95% CI 1.35, 1.46]) and hip (HR 1.25 [95% CI 1.19, 1.31]), as well as progression to joint replacement (HR 1.20 [95% CI 1.08, 1.33] for the knee and HR 1.22 [95% CI 1.08, 1.38] for the hip), while no association was found with inflammatory joint diseases. Individuals in the highest quintile of risk based on CRTAC1 level, age, sex, and body mass index had a 10-fold risk of knee or hip OA within 5 years compared to those in the lowest quintile. Adding aggrecan core protein (ACAN) and neurocan core protein (NCAN) to the model improved the prediction of OA but not joint replacement. Furthermore, we replicated the association of CUB domain-containing protein 1 with prior joint replacement.Conclusion. Plasma CRTAC1 is a specific biomarker for OA and a predictor of OA risk and progression to joint replacement. Adding ACAN and NCAN protein levels to the CRTAC1 model improved the prediction of OA.

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage

“…However, these results still need to be verified with large-sample validation. Fortunately, two recent large sample size studies both found plasma CRTAC1 as a specific candidate biomarker for OA and a predictor of OA risk and joint arthroplasty progression, 10,56 which reflects the reliability and further clinical research value of our screened key genes to a certain degree. However, the efficacy of plasma CRTAC1 in other ethnic populations and the optimal cutoff value need to be investigated further before clinical translation.…”

Decreased plasma cartilage acidic protein 1 in COVID‐19

“…We found no correlations between CRTAC1 concentrations and the domains of the SF-36 health survey. Determination of the reasons behind and significance of decreased CRTAC1 concentration in a subset of post-COVID-19 patients will require more detailed analysis of the roles of age, nature, and timing of the episode of COVID-19, and conditions that drive plasma CRTAC1 concentration up, such as osteoarthritis (Styrkarsdottir et al, 2021(Styrkarsdottir et al, , 2023Szilagyi et al, 2023;Tardif et al, 2022), or down, such idiopathic pulmonary fibrosis (Mayr et al, 2021) or COPD (this study). Importantly, longitudinal studies of CRTAC1 concentrations are needed post-COVID-19 in patients with and without symptoms of long COVID.…”

Development and Validation of a Deep-Learning Model to Predict Total Hip Replacement on Radiographs

“…T o date, none of the hip OA evaluation approaches can furnish sufficiently comprehensive data for reliable and precise predictions 31,32 . Therefore, we developed and validated a DCNN model to assess the risk of THA on the basis of baseline radiographs and clinical symptom data from 736 participants.…”