MicroRNA-140 plays dual roles in both cartilage development and homeostasis.
|
| 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.
|
|---|---|
| Authors | 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 |
| Journal | Genes & development (Genes Dev) Vol. 24 Issue 11 Pg. 1173-85 (Jun 01 2010) ISSN: 1549-5477 [Electronic] United States |
| PMID | 20466812 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!