Associations between joint effusion in the knee and gene expression levels in the circulation: a meta-analysis

Marjolein J Peters,André G Uitterlinden,Edwin H.G Oei,Albert Hofman,P Eline Slagboom,Sita M.A Bierma-Zeinstra,Dieuwke Schiphof,Joyce B.J Van Meurs,Margreet Kloppenburg,Johan L Bloem,Yolande F.M Ramos,Wouter Den Hollander,Ingrid Meulenbelt

doi:10.12688/f1000research.7763.1

Abstract

To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI. To investigate enriched pathways and protein-protein interactions, we used the DAVID and STRING webtools. In a meta-analysis, we identified 257 probes mapping to 189 unique genes in blood that were nominally significantly associated with joint effusion grades in the knee. Several compelling genes were identified such as C1orf38 and NFATC1. Significantly enriched biological pathways were: response to stress, gene expression, negative regulation of intracellular signal transduction, and antigen processing and presentation of exogenous pathways. Meta-analyses and subsequent enriched biological pathways resulted in interesting candidate genes associated with joint effusion that require further characterization. Associations were not transcriptome-wide significant most likely due to limited power. Additional studies are required to replicate our findings in more samples, which will greatly help in understanding the pathophysiology of OA and its relation to inflammation, and may result in biomarkers urgently needed to diagnose OA at an early stage.

Highlights

Osteoarthritis (OA) is a common, age-related, degenerative disease of the synovial joints
Mean body mass index (BMI) seemed to be higher with higher joint effusion grades, but due to small sample sizes this difference was not significant (ANOVA p-value Rotterdam Study (RS) = 0.069, ANOVA p-value GARP=0.487)
We examined whether joint effusion grades in the knee were associated with specific gene expression levels in the circulation, which could potentially serve as molecular biomarker to indicate OA in the early stage

Summary

Introduction

Osteoarthritis (OA) is a common, age-related, degenerative disease of the synovial joints It is characterized by cartilage degradation, osteophyte formation, subchondral bone changes, and synovitis[1]. These characteristics can lead to joint space narrowing, pain, and loss of function, until at the end-stage of the disease total joint replacement is required. To be able to change from symptomatic treatment at late disease state and total joint replacement towards early (secondary) prevention, it is very important to identify new osteoarthritic disease stage markers that could be measured in the early stages of OA These markers should function as new targets or biomarkers for early disease treatment and prevention

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Results

Conclusion