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

Shigeru MiyakiDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USATempei SatoDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Atsushi InoueDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Shuhei OtsukiDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA;Yoshiaki ItoDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Shigetoshi YokoyamaDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Yoshio KatoBiomedical Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8562, JapanFuko TakemotoDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Tomoyuki NakasaDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Satoshi YamashitaDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Shuji TakadaDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Martin LotzDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA;Hiroe Ueno-KudoDepartment of Systems Biomedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Hiroshi AsaharaDepartment of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA;

2010en

ABI

Annotatsiya

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.

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Identifikatorlar

DOI: 10.1101/gad.1915510

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