| Autor: |
Yizheng Wu, Shuying Shen, Jiaxin Chen, Weiyu Ni, Qinxin Wang, Hongyi Zhou, Junxin Chen, Haitao Zhang, Zixuan Mei, Xuewu Sun, Panyang Shen, Zhiwei Jie, Wenbin Xu, Zhenghua Hong, Yan Ma, Kefan Wang, Shuanglin Wan, Hongfei Wu, Ziang Xie, An Qin, Shunwu Fan |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Science Advances. 9 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.ade5584 |
| Popis: |
Osteoarthritis (OA) is a degenerative disease with a series of metabolic changes accompanied by many altered enzymes. Here, we report that the down-regulated dimethylarginine dimethylaminohydrolase-1 (DDAH1) is accompanied by increased asymmetric dimethylarginine (ADMA) in degenerated chondrocytes and in OA samples. Global or chondrocyte-conditional knockout of ADMA hydrolase DDAH1 accelerated OA development in mice. ADMA induces the degeneration and senescence of chondrocytes and reduces the extracellular matrix deposition, thereby accelerating OA progression. ADMA simultaneously binds to SOX9 and its deubiquitinating enzyme USP7, blocking the deubiquitination effects of USP7 on SOX9 and therefore leads to SOX9 degradation. The ADMA level in synovial fluids of patients with OA is increased and has predictive value for OA diagnosis with good sensitivity and specificity. Therefore, activating DDAH1 to reduce ADMA level might be a potential therapeutic strategy for OA treatment. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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