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

作者：Miyaki Shigeru; Sato Tempei; Inoue Atsushi; Otsuki Shuhei; Ito Yoshiaki; Yokoyama Shigetoshi; Kato Yoshio; Takemoto Fuko; Nakasa Tomoyuki; Yamashita Satoshi; Takada Shuji; Lotz Martin K; Ueno Kudo Hiroe; Asahara Hiroshi^*

来源：Genes & Development, 2010, 24(11): 1173-1185.

DOI：10.1101/gad.1915510

• MicroRNA
• miR-140
• osteoarthritis
• cartilage
• Adamts-5

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.

• 出版日期2010-6-1