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Macro view of microRNA function in osteoarthritis

Nature Reviews Rheumatology volume 8, pages 543–552 (2012)Cite this article

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Abstract

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

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Figure 1: OA pathogenesis and the putative role of miRNA.
Figure 2: Molecular machinery behind the biological functions of miRNA.
Figure 3: Dual roles of miR-140 in endochondral bone development and articular cartilage homeostasis.
Figure 4: Co-administration of miRNA mimics have potential for synergistic functions in maintaining or, perhaps, restoring joint health.

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Acknowledgements

This work is partly supported by the NIH (USA; grant numbers AR050631 and AR056120), the Arthritis National Research Foundation (USA), Health and Labour Sciences Research Grants (Ministry of Health, Labour and Welfare, Japan), Grants-in-Aid for Scientific Research (Ministry of Education, Culture, Sports, Science and Technology, Japan), the National Center for Child Health and Development (Japan; 20A-3) and CREST (Japan Science and Technology Agency).

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  1. Department of Regenerative Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Hiroshima, 734-8551, Japan

    Shigeru Miyaki

  2. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Hiroshi Asahara

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Correspondence to Hiroshi Asahara.

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Miyaki, S., Asahara, H. Macro view of microRNA function in osteoarthritis. Nat Rev Rheumatol 8, 543–552 (2012). https://doi.org/10.1038/nrrheum.2012.128

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