期刊
OSTEOARTHRITIS AND CARTILAGE
卷 23, 期 7, 页码 1214-1220出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2015.02.015
关键词
microRNA; Drosha; Prg4; Chondrocyte; Osteoarthritis; Articular cartilage
资金
- NIAMS NIH HHS [AR056645, P30 AR066261, R01 AR056645] Funding Source: Medline
Objective: In growth plate chondrocytes, loss of Dicer, a microRNA (miRNA)-processing enzyme, causes defects in proliferation and differentiation, leading to a lethal skeletal dysplasia. However roles of miRNAs in articular chondrocytes have not been defined in vivo. To investigate the role of miRNAs in articular chondrocytes and to explore the possibility of generating a novel mouse osteoarthritis (OA) model caused by intrinsic cellular dysfunction, we ablated Drosha, another essential enzyme for miRNA biogenesis, exclusively in articular chondrocytes of postnatal mice. Design: First, to confirm that the essential role of miRNAs in skeletal development, we ablated the miRNA biogenesis pathway by deleting Drosha or DGCR8 in growth plate chondrocytes. Next, to investigate the role of miRNAs in articular cartilage, we deleted Drosha using Prg4-CreERT transgenic mice expressing a tamoxifen-activated Cre recombinase (CreERT) exclusively in articular chondrocytes. Tamoxifen was injected at postnatal days, 7, 14, 21, and 28 to ablate Drosha. Results: Deletion of Drosha or DGCR8 in growth plate chondrocytes caused a lethal skeletal defect similar to that of Dicer deletion, confirming the essential role of miRNAs in normal skeletogenesis. Early postnatal Drosha deletion in articular chondrocytes significantly increased cell death and decreased SafraninO staining. Mild OA-like changes, including surface erosion and cleft formation, were found in male mice at 6 months of age; however such changes in females were not observed even at 9 months of age. Conclusions: Early postnatal Drosha deficiency induces articular chondrocyte death and can cause a mild OA-like pathology. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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