The acetabular labrum tissue shows unique transcriptome signatures compared to cartilage and responds to combined cyclic compression and surface shearing

Abstract

The labrum is a fibrocartilaginous ring surrounding the acetabulum. Loss of labrum function contributes to the degeneration of the hip joint, leading to osteoarthritis. Successful labrum restoration requires profound knowledge about the tissue being replaced. The aim of this study was to characterize the transcriptome and the mechanobiological function of the labrum.RNA-seq was performed to compare the transcriptome of bovine labrum against articular cartilage tissue. Differential expression and gene ontology (GO) term pathway analysis were applied using the SUSHI framework. Bovine labrum explants were cultured for 5 days with / without mechanical loading and targeted gene expression was analyzed by real time quantitative polymerase chain reaction.More than 6′000 genes were significantly differentially expressed in the labrum compared to cartilage. Up- and downregulated genes were associated with the GO term extracellular matrix organization. The study established an extracellular matrix gene expression profile of healthy labrum tissue and identified significantly upregulated extracellular matrix related genes compared to cartilage tissue. Mechanical loading significantly upregulated aggrecan (ACAN), cartilage oligomeric matrix protein (COMP), fibronectin (FN1) and proteoglycan 4 (PRG4). MMP1/3/9 and IL6, which were upregulated by an inflammatory stimulus (IL-1b), were statistically unaffected by the loading, although IL6 was upregulated in each donor immediately after the loading.Unique ECM related features may guide the development of labrum tissue-engineering solutions. Despite the transcriptome differences between labrum and cartilage tissue, gene expression response to mechanical loading showed similarities with previously reported responses in cartilage, indicating a preserved tissue adaptation mechanism to mechanical loading.Running title: Acetabular Labrum Mechanobiology.