Macro view of microRNA function in osteoarthritis

• Published in: Nature reviews. Rheumatology Vol. 8; no. 9; pp. 543 - 552
• Main Authors: Miyaki, Shigeru, Asahara, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2012; Nature Publishing Group
• Subjects: 631/208/200; 631/337/384/331; 631/80/304; 692/699/1670/407; Animals; Arthritis; Biomarkers - metabolism; Cartilage; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cell death; Chondrocytes - metabolism; Development and progression; Disease; Disease Models, Animal; Enzymes; Gene Expression Regulation - physiology; Genes; Genetic aspects; Genetic engineering; Health aspects; Hepatitis C; Homeostasis; Homeostasis - genetics; Humans; Medicine; Medicine & Public Health; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - therapeutic use; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteoarthritis - physiopathology; Pathogenesis; review-article; Rheumatology; RNA-Induced Silencing Complex - genetics; Signal Transduction; United States; Japan
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/nrrheum.2012.128

MicroRNAs (miRNAs) function in several chronic diseases—miRNA-mediated fine control of genetic networks involved in tissue development and homeostasis becomes disrupted. Participating in production and maintenance of articular chondrocytes and skeletogenesis, miRNA are increasingly implicated in the pathogenesis of osteoarthritis. Data from animal and cell studies are discussed in this Review, alongside the potential for targeting miRNA in the clinic. Osteoarthritis (OA), the most common musculoskeletal disorder, is complex, multifaceted, and characterized by degradation of articular cartilage and alterations in other joint tissues. Although some pathogenic pathways have been characterized, current knowledge is incomplete and effective approaches to the prevention or treatment of OA are lacking. Understanding novel molecular mechanisms that are involved in the maintenance and destruction of articular cartilage, including extracellular regulators and intracellular signalling mechanisms in joint cells that control cartilage homeostasis, has the potential to identify new therapeutic targets in OA. MicroRNAs control tissue development and homeostasis by fine-tuning gene expression, with expression patterns specific to tissues and developmental stages, and are increasingly implicated in the pathogenesis of complex diseases such as cancer and cardiovascular disorders. The emergent roles of microRNAs in cartilage homeostasis and OA pathogenesis are summarized in this Review, alongside potential clinical applications. Key Points Although some pathogenic pathways in osteoarthritis (OA) have been characterized, effective approaches to prevention or treatment of OA are lacking Novel genetic regulators, microRNAs (miRNAs), are involved in the development of the musculoskeletal system and OA pathogenesis through maintenance of articular chondrocytes miRNAs have a role in transmitting the effects of the main risk factors for OA, such as ageing and inflammation, onto cellular homeostasis through their control of multiple target genes Approaches to maintaining or suppressing the expression of key miRNAs in OA pathogenesis have the potential to identify new therapeutic and diagnostic targets