氧化应激
骨关节炎
软骨
骨量减少
活性氧
细胞生物学
疾病
骨质疏松症
医学
生物
生物信息学
内科学
病理
解剖
替代医学
骨矿物
作者
F.M. Cornelis,S. Monteagudo,Laura-An Guns,Wouter den Hollander,Rob G. H. H. Nelissen,L. Storms,Tine Peeters,Ilse Jonkers,Ingrid B. Borecki,Rik Lories
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2018-09-12
卷期号:10 (458)
被引量:29
标识
DOI:10.1126/scitranslmed.aar8426
摘要
Osteoarthritis is the most common joint disorder with increasing global prevalence due to aging of the population. Current therapy is limited to symptom relief, yet there is no cure. Its multifactorial etiology includes oxidative stress and overproduction of reactive oxygen species, but the regulation of these processes in the joint is insufficiently understood. We report that ANP32A protects the cartilage against oxidative stress, preventing osteoarthritis development and disease progression. ANP32A is down-regulated in human and mouse osteoarthritic cartilage. Microarray profiling revealed that ANP32A protects the joint by promoting the expression of ATM, a key regulator of the cellular oxidative defense. Antioxidant treatment reduced the severity of osteoarthritis, osteopenia, and cerebellar ataxia features in Anp32a-deficient mice, revealing that the ANP32A/ATM axis discovered in cartilage is also present in brain and bone. Our findings indicate that modulating ANP32A signaling could help manage oxidative stress in cartilage, brain, and bone with therapeutic implications for osteoarthritis, neurological disease, and osteoporosis.
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