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

Shigeru Miyaki, Tempei Sato, Atsushi Inoue, Shuhei Otsuki, Yoshiaki Ito, Shigetoshi Yokoyama, Yoshio Kato, Fuko Takemoto, Tomoyuki Nakasa, Satoshi Yamashita, Shuji Takada, Martin K. Lotz, Hiroe Ueno-Kudo, Hiroshi Asahara

Research output: Contribution to journalArticlepeer-review

500 Scopus citations

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 amouse line through a targeted deletion of miR-140.miR-140-/- mice manifested amild 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.

Original languageEnglish (US)
Pages (from-to)1173-1185
Number of pages13
JournalGenes and Development
Volume24
Issue number11
DOIs
StatePublished - Jun 1 2010

All Science Journal Classification (ASJC) codes

  • General Medicine

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