Research ArticleOsteoarthritis

ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone

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Science Translational Medicine  12 Sep 2018:
Vol. 10, Issue 458, eaar8426
DOI: 10.1126/scitranslmed.aar8426

Oxidative stress and osteoarthritis

Osteoarthritis is a common degenerative joint disorder that affects cartilage and bone. Cornelis et al. investigated the role of ANP32A, a protein involved in multiple cellular processes, in osteoarthritis. ANP32A was decreased in osteoarthritic human and mouse tissue samples and also decreased with aging. The authors found that ANP32A promoted transcription of ATM and regulated reactive oxygen species in cartilage. Antioxidant therapy protected Anp32a-deficient mice from developing osteoarthritis and osteopenia and also rescued neurological defects caused by lack of ATM and increased oxidative stress. These results suggest that ANP32A could be a therapeutic target for correcting imbalanced reactive oxygen species and antioxidants.


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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