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DOI | 10.1038/s41467-019-10700-4 |
DOT1L safeguards cartilage homeostasis and protects against osteoarthritis | |
Monteagudo, Silvia1; Cornelis, Frederique M. F.1; Aznar-Lopez, Carolina1; Yibmantasiri, Ploi1; Guns, Laura-An1; Carmeliet, Peter2,3; Cailotto, Frederic1,4; Lories, Rik J.1,5 | |
2019-06-27 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Belgium; France |
英文摘要 | Osteoarthritis is the most prevalent and crippling joint disease, and lacks curative treatment, as the underlying molecular basis is unclear. Here, we show that DOT1L, an enzyme involved in histone methylation, is a master protector of cartilage health. Loss of DOT1L disrupts the molecular signature of healthy chondrocytes in vitro and causes osteoarthritis in mice. Mechanistically, the protective function of DOT1L is attributable to inhibition of Wnt signalling, a pathway that when hyper-activated can lead to joint disease. Unexpectedly, DOT1L suppresses Wnt signalling by inhibiting the activity of sirtuin-1 (SIRT1), an important regulator of gene transcription. Inhibition of SIRT1 protects against osteoarthritis triggered by loss of DOT1L activity. Modulating the DOT1L network might therefore be a therapeutic approach to protect the cartilage against osteoarthritis. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000403605400001 |
WOS关键词 | ARTICULAR CHONDROCYTES ; GENE-EXPRESSION ; H3K79 METHYLATION ; SIRT1 ; WNT ; TRANSCRIPTION ; ACTIVATION ; TARGET ; PROGRESSION ; RESVERATROL |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204433 |
专题 | 资源环境科学 |
作者单位 | 1.Katholieke Univ Leuven, Lab Tissue Homeostasis & Dis, Skeletal Biol & Engn Res Ctr, Dept Dev & Regenerat, B-3000 Leuven, Belgium; 2.Katholieke Univ Leuven, Lab Angiogenesis & Vasc Metab, Dept Oncol, B-3000 Leuven, Belgium; 3.VIB, Lab Angiogenesis & Vasc Metab, Vesalius Res Ctr, B-3000 Leuven, Belgium; 4.Biopole Univ Lorraine, CNRS Univ Lorraine, UMR7365, IMoPA, Campus Biol Sante, F-54500 Vandoeuvre Les Nancy, France; 5.Univ Hosp Leuven, Div Rheumatol, B-3000 Louvain, Belgium |
推荐引用方式 GB/T 7714 | Monteagudo, Silvia,Cornelis, Frederique M. F.,Aznar-Lopez, Carolina,et al. DOT1L safeguards cartilage homeostasis and protects against osteoarthritis[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Monteagudo, Silvia.,Cornelis, Frederique M. F..,Aznar-Lopez, Carolina.,Yibmantasiri, Ploi.,Guns, Laura-An.,...&Lories, Rik J..(2019).DOT1L safeguards cartilage homeostasis and protects against osteoarthritis.NATURE COMMUNICATIONS,8. |
MLA | Monteagudo, Silvia,et al."DOT1L safeguards cartilage homeostasis and protects against osteoarthritis".NATURE COMMUNICATIONS 8(2019). |
条目包含的文件 | 条目无相关文件。 |
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