MicroRNA-140 plays dual roles in both cartilage development and homeostasis

  1. Hiroshi Asahara1,2,5
  1. 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA;
  2. 2Department of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;
  3. 3Biomedical Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8562, Japan
    1. 4 These authors contributed equally to this work.

    Abstract

    Osteoarthritis (OA), the most prevalent aging-related joint disease, is characterized by insufficient extracellular matrix synthesis and articular cartilage degradation, mediated by several proteinases, including Adamts-5. miR-140 is one of a very limited number of noncoding microRNAs (miRNAs) specifically expressed in cartilage; however, its role in development and/or tissue maintenance is largely uncharacterized. To examine miR-140 function in tissue development and homeostasis, we generated a mouse line through a targeted deletion of miR-140. miR-140−/− mice manifested a mild skeletal phenotype with a short stature, although the structure of the articular joint cartilage appeared grossly normal in 1-mo-old miR-140−/− mice. Interestingly, miR-140−/− mice showed age-related OA-like changes characterized by proteoglycan loss and fibrillation of articular cartilage. Conversely, transgenic (TG) mice overexpressing miR-140 in cartilage were resistant to antigen-induced arthritis. OA-like changes in miR-140-deficient mice can be attributed, in part, to elevated Adamts-5 expression, regulated directly by miR-140. We show that miR-140 regulates cartilage development and homeostasis, and its loss contributes to the development of age-related OA-like changes.

    Keywords

    Footnotes

    • Received February 10, 2010.
    • Accepted April 13, 2010.

    Related Article

    | Table of Contents

    Life Science Alliance