Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis

Ravindra Kolhe,Ashis K Mondal,Ravirajsinh N Jadeja,Michelle Drewry,Monte Hunter,Yutao Liu,Robert E Guldberg,Chetan Pundkar,Sadanand Fulzele,Carlos M Isales,Mark W Hamrick,Mumtaz V Rojiani,Siyang Liu,Bharati Mendhe

doi:10.1038/s41598-017-01905-y

Ravindra Kolhe, Ashis K Mondal + Show 12 more

Open Access

https://doi.org/10.1038/s41598-017-01905-y

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Abstract

The pathogenesis of osteoarthritis (OA) is poorly understood, and therapeutic approaches are limited to preventing progression of the disease. Recent studies have shown that exosomes play a vital role in cell-to-cell communication, and pathogenesis of many age-related diseases. Molecular profiling of synovial fluid derived exosomal miRNAs may increase our understanding of OA progression and may lead to the discovery of novel biomarkers and therapeutic targets. In this article we report the first characterization of exosomes miRNAs from human synovial fluid. The synovial fluid exosomes share similar characteristics (size, surface marker, miRNA content) with previously described exosomes in other body fluids. MiRNA microarray analysis showed OA specific exosomal miRNA of male and female OA. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified gender-specific target genes/signaling pathways. These pathway analyses showed that female OA specific miRNAs are estrogen responsive and target TLR (toll-like receptor) signaling pathways. Furthermore, articular chondrocytes treated with OA derived extracellular vesicles had decreased expression of anabolic genes and elevated expression of catabolic and inflammatory genes. In conclusion, synovial fluid exosomal miRNA content is altered in patients with OA and these changes are gender specific.

Highlights

Osteoarthritis (OA) is a degenerative joint disease affecting 14% of adults aged 25 years and older and 34% of those older than 65 in the United States[1]
Synovial fluid is useful for monitoring pathophysiological changes in the joint space because of its direct and intimate relationship with synovial membrane, articular cartilage and other tissue types of knee joint
Skriner et al previously reported that synovial exosomes of rheumatoid arthritis (RA) patients with reactive arthritis, and patients with osteoarthritis, contain citrullinated proteins[7]

Summary

Introduction

Osteoarthritis (OA) is a degenerative joint disease affecting 14% of adults aged 25 years and older and 34% of those older than 65 in the United States[1]. Exosomes are small (40–100 nm diameter) vesicles containing specific proteins, lipids, and RNA molecules that are secreted by cells into the extracellular space[8,9,10,11,12]. These EVs are recognized to play a vital role in several age-related diseases[12,13,14]. A set of microRNAs (miRNAs) captured in EVs secreted by the knee joint in synovial fluid has high potential as a biomarker for early and accurate diagnosis of OA. We identified both differential expression of miRNAs in synovial fluid from OA patients and gender specific miRNAs within the OA population

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