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

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.

Exosomes: biology, therapeutic potential, and emerging role in musculoskeletal repair and regeneration

“…Exosomes derived from the synovial fluid of OA patients stimulated the release of proinflammatory factors from M1 macrophages . Moreover, articular chondrocytes treated with exosomes derived from the synovial fluid of OA patients had decreased expression of anabolic genes and elevated expression of catabolic and inflammatory genes, suggesting a pathologic role for these exosomes in OA progression …”

“…These tumor‐specific miRNAs or proteins carried in exosomes have been suggested to be biomarkers of lung cancer, prostate cancer, breast cancer, ovarian cancer, and other types of cancer . Exosomes may also be promising biomarkers for acute ischemic stroke, kidney disease, inflammatory bowel disease, Alzheimer's disease, and osteoarthritis (OA) …”

Extracellular vesicles in bone and tooth: A state‐of‐art paradigm in skeletal regeneration

“…These particles function as message carriers by the transfer of proteins and genetic information into adjacent or distant cells (Ge, Ke, Cai, Yang, & Mu, 2015;Valadi et al, 2007). By transporting coding RNA, noncoding RNA, proteins, antigen presentation molecules, and DNA, EVs have been proposed to participate in not only normal physiological processes, such as the induction of immune responses (Thery et al, 2002) and organogenesis (Jiang et al, 2017) but also the development and progression of diseases, such as musculoskeletal diseases (Kolhe et al, 2017;Tao et al, 2017), neurodegenerative diseases (Kapogiannis et al, 2015), and tumor/cancer (Shao et al, 2016). Interestingly, nearly all kinds of cells derived from tooth and bone release EVs that partly inherit the genetic characteristics of their parent cells.…”

Emerging Role of Exosomes in the Joint Diseases

“…To investigate gender differences in OA prevalence, Kolhe et al compared SF exosomes between women and men with OA and non-OA. They found the miRNA content of EVs differed between OA and non-OA groups and between genders [13]. The Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis for downregulated miRNAs in OA for both genders showed glycan degradation, cell adhesion molecules and mucin type O-glycan biosynthesis were involved.…”

“…ONFH is a joint disease with femoral head ischemia that may be caused by hip trauma, alcohol abuse, corticosteroids overuse or some hematological diseases. ONFH involves the necrosis of cancellous bone and ultimately the collapse of the femoral head [13]. RA is a chronic autoimmune joint disease with inflammatory synovitis, degradation of articular cartilage, erosion of the marginal bone, systemic immune and inflammatory manifestations [14].…”