Identification of long non-coding RNAs expressed in knee and hip osteoarthritic cartilage

B Ajekigbe,K Cheung,Y Xu,A.J Skelton,A Panagiotopoulos,J Soul,T.E Hardingham,D.J Deehan,M.J Barter,D.A Young

doi:10.1016/j.joca.2018.12.015

B Ajekigbe, K Cheung + Show 8 more

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https://doi.org/10.1016/j.joca.2018.12.015

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SummaryObjectiveLong intergenic non-coding RNAs (lincRNAs) are emerging as key regulators in gene expression; however, little is known about the lincRNA expression changes that occur in osteoarthritis (OA). Here we aimed to define a transcriptome of lncRNAs in OA cartilage, specifically comparing the lincRNA transcriptome of knee and hip cartilage.MethodRNA-seq was performed on nucleic acid extracted from hip cartilage from patients undergoing joint replacement surgery because of either OA (n = 10) or because of a neck of femur fracture (NOF; n = 6). After transcript alignment, counts were performed using Salmon and differential expression for ENSEMBL lincRNAs determined using DESeq2. Hip RNA-seq lincRNA expression was compared to a knee dataset (ArrayExpress; E-MTAB-4304). ChIP-seq data from ENCODE was used to determine whether lincRNAs were associated with promoters (plncRNA) or unidirectional enhancer-like regulatory elements (elncRNAs).ResultsOur analysis of the hip transcriptome identified 1692 expressed Transcripts Per Million (TPM ≥1) Ensembl lincRNAs, of which 198 were significantly (FDR ≤0.05) differentially expressed in OA vs normal (NOF) cartilage. Similar analysis of knee cartilage transcriptome identified 648 Emsembl lincRNAs with 93 significantly (FDR ≤0.05) differentially expressed in intact vs damaged cartilage. In total, 1834 lincRNAs were expressed in both hip and knee cartilage, with a highly significant correlation in expression between the two cartilages.ConclusionThis is the first study to use RNA-seq to map and compare the lincRNA transcriptomes of hip and knee cartilage. We propose that lincRNAs expressed selectively in cartilage, or showing differential expression in OA, will play a role in cartilage homoeostasis.

Highlights

Osteoarthritis (OA) is a common debilitating musculoskeletal disease that affects the articulating joints and for which there remains no cure
We performed RNA sequencing (RNA-seq) on cartilage RNA extracted from OA and neck of femur fracture (NOF) patients undergoing total hip arthroplasty
We identified 198 lincRNAs altered in hip OA progression and 93 in damaged knee cartilage of which 20 were in common

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Introduction

Osteoarthritis (OA) is a common debilitating musculoskeletal disease that affects the articulating joints and for which there remains no cure. The burden of OA continues to increase worldwide. In the United Kingdom, 89,288 hip and 98,591 knee primary replacements were recorded in the National Joint Registry in 2015, with the vast majority attributable to OA1. OA is characterised by pain, stiffness and deformity of the affected joint with loss of function. There is degradation and loss of articular cartilage with subsequent sclerosis of the underlying bone. Changes to chondrocytes and the composition of the extracellular matrix have been extensively investigated, with a maladaptive milieu of growth factors, inflammatory cytokines (e.g., Tumour Necrosis Factor a; TNFa) and degradative enzymes such as matrix metalloproteinases (MMPs) contributing to cartilage destruction[2]

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