期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 10, 期 458, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aar8426
关键词
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资金
- Flanders Research Foundation (FWO-Vlaanderen)
- Interuniversity Attraction Poles (IUAP) network Development and Repair (Belspo) [IUAP-VII/07]
- FP7 project Translational Research in Europe Applied Technologies for Osteoarthritis (Treat-OA, European Commission framework 7 programme grant ) [200800]
- Dutch Arthritis Association [DAA_10_1-402]
- Dutch Scientific Research council NWO/ZonMW VICI scheme [91816631/52]
- Leiden University Medical Center
- Marie-Curie Intra-European postdoctoral fellowships
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. Micro-array 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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