ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone.
Sci Transl Med
; 10(458)2018 09 12.
Article
em En
| MEDLINE
| ID: mdl-30209244
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Osso e Ossos
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Encéfalo
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Proteínas Nucleares
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Cartilagem
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Estresse Oxidativo
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas Mutadas de Ataxia Telangiectasia
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article