Expression of MicroRNA‐146a in osteoarthritis cartilage

Abstract

Objective. A role of microRNA, which are ϳ22-nucleotide noncoding RNAs, has recently been recognized in human diseases. The objective of this study was to identify the expression pattern of microRNA-146a (miR-146a) in cartilage from patients with osteoarthritis (OA).Methods. The expression of miR-146a in cartilage from 15 patients with OA was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization. Induction of the expression of miR-146a by cultures of normal human articular chondrocytes following stimulation with interleukin-1␤ (IL-1␤) was examined by quantitative RT-PCR.Results. All cartilage samples were divided into 3 groups according to a modification of the Mankin score (grade I ‫؍‬ mild OA scored 0-5, grade II ‫؍‬ moderate OA scored 6-10, and grade III ‫؍‬ severe OA scored 11-14). In grade I OA cartilage samples, the expression of miR-146a and COL2A1 was significantly higher than that in the other groups (P < 0.05). In grades II and III OA cartilage, the expression of miR-146a and COL2A1 was decreased, whereas the expression of matrix metalloproteinase 13 (MMP-13) was elevated in grade II OA cartilage. These data showed that miR-146a is expressed intensely in cartilage with a low Mankin grade and that miR-146a expression decreases in parallel with the level of MMP-13 expression. Tissue section in situ hybridization of primary miR-146a (pri-miR-146a) revealed that pri-miR-146a was expressed in chondrocytes residing in all tissue layers, especially in the superficial layer, where it was intensely expressed. The expression of miR-146 was markedly elevated by IL-1␤ stimulation in human chondrocytes in vitro. Conclusion. This study shows that miR-146 is intensely expressed in low-grade OA cartilage and that its expression is induced by stimulation of IL-1␤. Thus, miR-146 might play a role in OA cartilage pathogenesis.Osteoarthritis (OA) is a highly prevalent disease that is characterized by progressive degeneration of articular cartilage (1-4). Although little is known about the pathogenesis of OA, an imbalance between anabolic and catabolic factors that maintain the homeostasis of cartilage is thought to lead to cartilage degradation. While there is a delicate balance between anabolism and catabolism in the strict regulation of matrix turnover in normal cartilage, catabolism becomes dominant over anabolism in OA cartilage, leading to the degradation of cartilage. Several studies have demonstrated an interaction between anabolic factors, such as transforming growth factor ␤, and catabolic factors, such as matrix metalloproteinases (MMPs) and aggrecanases, in chondrocytes; however, the molecular mechanisms involved in OA remain unclear (5).MicroRNA (miRNA) are a family of ϳ22-nucleotide noncoding RNAs identified in organisms ranging from nematodes to humans (6-8). Many miRNA are evolutionarily conserved across phyla, regulating gene expression by posttranscriptional gene repression. The miRNA regulate gene expression by binding the 3Ј-untranslated region of...

MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN

“…Yamasaki et al . reported that inflammatory cytokines induced miR‐146a expression might negatively regulate catabolic factors such as MMP13 expression through miR‐146‐negative feedback including down‐regulation of IRAK1 and TRAF6 in early OA cartilage 24. A study by Bo Yang et al .…”

Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism

“…First, the expression of miR‐146a was stimulated by inflammatory factors such as interleukin 1 and tumor necrosis factor‐alpha (Sheedy & O'Neill, 2008). It was one of the first microRNAs associated with OA cartilage (Yamasaki et al., 2009). miR‐146a operates to fine‐tune inflammatory responses via a “negative regulatory loop” (Ma, Becker Buscaglia, Barker & Li, 2011).…”

“…Yamasaki et al. observed that miR‐146a is stimulated by IL‐1 and expressed intensely in mild OA cartilage (Yamasaki et al., 2009). However, in moderate and severe OA samples, miR‐146a expression is significantly decreased, in parallel to the increase in MMP‐13 level (Yamasaki et al., 2009).…”

“…observed that miR‐146a is stimulated by IL‐1 and expressed intensely in mild OA cartilage (Yamasaki et al., 2009). However, in moderate and severe OA samples, miR‐146a expression is significantly decreased, in parallel to the increase in MMP‐13 level (Yamasaki et al., 2009). These evidences suggest that miR‐146a is stimulated by the increase in IL‐1 to counteract MMP‐13 upregulation and cartilage degeneration during OA pathogenesis.…”

MicroRNA‐199a‐3p, microRNA‐193b, and microRNA‐320c are correlated to aging and regulate human cartilage metabolism

“…2 Abnormalities in cartilage development have been observed in Dicer gene dysfunction models, and miRNA is known to play a key role in cartilage differentiation. 3 miRNA plays a key role in differentiation and growth in organs and tissues, 2 and miRNAs expressed specifically in cartilage [4][5][6][7][8] have been reported. Till date, miR21, 4 miR22, 9 miR27a, 6 miR140, 10 and miR146 8 have been reported as miRNAs that are associated with cartilage metabolism.…”