Signature of circulating microRNAs in osteoarthritis

Abstract

Background Osteoarthritis is the most common form of arthritis and a major socioeconomic burden. Our study is the first to explore the association between serum microRNA levels and the development of severe osteoarthritis of the knee and hip joint in the general population. Methods We followed 816 Caucasian individuals from 1995 to 2010 and assessed joint arthroplasty as a definitive outcome of severe osteoarthritis of the knee and hip. After a microarray screen, we validated 12 microRNAs by real-time PCR in the entire cohort at baseline. Results In Cox regression analysis, three microRNAs were associated with severe knee and hip osteoarthritis. let-7e was a negative predictor for total joint arthroplasty with an adjusted HR of 0.75 (95% CI 0.58 to 0.96; p=0.021) when normalised to U6, and 0.76 (95% CI 0.6 to 0.97; p=0.026) after normalisation to the Ct average. miRNA-454 was inversely correlated with severe knee or hip osteoarthritis with an adjusted HR of 0.77 (95% CI 0.61 to 0.97; p=0.028) when normalised to U6. This correlation was lost when data were normalised to Ct average (p=0.118). Finally, miRNA-885-5p showed a trend towards a positive relationship with arthroplasty when normalised to U6 (HR 1.24; 95% CI 0.95 to 1.62; p=0.107) or to Ct average (HR 1.30; 95% CI 0.99 to 1.70; p=0.056). Conclusions Our study is the first to identify differentially expressed circulating microRNAs in osteoarthritis patients necessitating arthroplasty in a large, population-based cohort. Among these microRNAs, let-7e emerged as potential predictor for severe knee or hip osteoarthritis.

Emerging targets in osteoarthritis therapy

“…Our recent ability to profile unique patterns of epigenetic changes offers novel strategies for distinguishing diverse chondrocyte phenotypes that relate to chondrogenic programming, articular cartilage homeostasis, and OA disease progression, and for identifying novel biomarkers of early OA, such as circulating long non-coding RNAs and miRNAs [154,155]. Correlating DNA methylation, chromatin marks, and miRNA signatures in human OA disease with those found in well-defined OA animal models could allow us to define the different regulatory requirements for stress-related phenotypes of OA chondrocytes [156].…”

Serum MicroRNA Signatures in Migraineurs During Attacks and in Pain-Free Periods

“…MiRNAs frequently exhibit imperfect complementarity with their target strands, which allows one specific miRNA to inhibit the expression of multiple genes [7]. Recently, a number of studies have been published pertaining to the role of miRNAs in both inflammatory and neuropathic pain conditions [8][9][10], and a few studies have successfully applied circulating miRNAs as biomarkers in pain conditions such as osteoarthritis, complex regional pain syndrome (CRPS), fibromyalgia, and irritable bowel syndrome in humans [8,[11][12][13][14][15]. Additionally, a pioneering study highlighted the ability of interstitial miR-let-7b to induce pain through an extracellular mechanism involving the coupling between Toll-like receptor-7 and the nociceptive ion channel transient receptor potential cation channel subfamily A [16].…”

Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration

“…miR-146 is another miRNA that is highly expressed in low-grade OA cartilage and is induced by IL-1β stimulation; additionally, it mediates chondrocyte apoptosis (13,14). In serum, Beyer et al recently reported miRNA let-7e as a potential predictor for severe knee or hip OA (15).…”