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

Genes Dev. 2010 Jun 1;24(11):1173-85. doi: 10.1101/gad.1915510. Epub 2010 May 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism
  • ADAMTS5 Protein
  • Animals
  • Bone Development / genetics
  • Cartilage / growth & development*
  • Homeostasis / genetics
  • Homeostasis / physiology*
  • Knee Joint / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Osteoarthritis / pathology


  • MIRN140 microRNA, mouse
  • MicroRNAs
  • ADAM Proteins
  • ADAMTS5 Protein
  • Adamts5 protein, mouse