In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 24, No. 11 ( 2010-06-01), p. 1173-1185
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.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2010
detail.hit.zdb_id:
1467414-2
SSG:
12
