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

被引：498

作者：

Miyaki, Shigeru ^{[1
]}

Sato, Tempei ^{[2
]}

Inoue, Atsushi ^{[2
]}

Otsuki, Shuhei ^{[1
]}

Ito, Yoshiaki ^{[2
]}

Yokoyama, Shigetoshi ^{[2
]}

Kato, Yoshio ^{[3
]}

Takemoto, Fuko ^{[2
]}

Nakasa, Tomoyuki ^{[2
]}

Yamashita, Satoshi ^{[2
]}

Takada, Shuji ^{[2
]}

Lotz, Martin K. ^{[1
]}

Ueno-Kudo, Hiroe ^{[2
]}

Asahara, Hiroshi ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[2] Natl Res Inst Child Hlth & Dev, Dept Syst Biomed, Tokyo 1578535, Japan

[3] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst Cell Engn RICE, Tsukuba, Ibaraki 3058562, Japan

来源：

GENES & DEVELOPMENT | 2010年 / 24卷 / 11期

基金：

新加坡国家研究基金会;

关键词：

MicroRNA; miR-140; osteoarthritis; cartilage; Adamts-5; HISTONE DEACETYLASE-4; RHEUMATOID-ARTHRITIS; SYNOVIAL TISSUE; COLLAGEN GENE; OSTEOARTHRITIS; EXPRESSION; MICE; MOUSE; DEGRADATION; DIFFERENTIATION;

D O I：

10.1101/gad.1915510

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1173 / 1185

页数：13