{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:18:41Z","timestamp":1790839121751,"version":"4.1.0"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,1,27]]},"abstract":"<jats:p>Degenerative diseases affecting the nervous and skeletal systems affect the health of millions of elderly people. Optineurin (OPTN) has been associated with numerous neurodegenerative diseases and Paget\u2019s disease of bone (PDB), a degenerative bone disease initiated by hyperactive osteoclastogenesis. In this study, we found age-related increase in OPTN and nuclear factor E2-related factor 2 (NRF2) in vivo. At the molecular level, OPTN could directly interact with both NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) for up-regulating antioxidant response. At the cellular level, deletion of OPTN resulted in increased intracellular reactive oxygen species and increased osteoclastogenic potential. At the tissue level, deletion of OPTN resulted in substantially increased oxidative stress derived from leukocytes that further stimulate osteoclastogenesis. Last, curcumin attenuated hyperactive osteoclastogenesis induced by OPTN deficiency in aged mice. Collectively, our findings reveal an OPTN-NRF2 axis maintaining bone homeostasis and suggest that antioxidants have therapeutic potential for PDB.<\/jats:p>","DOI":"10.1126\/sciadv.ade6998","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T14:02:24Z","timestamp":1674828144000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":30,"title":["Optineurin regulates NRF2-mediated antioxidant response in a mouse model of Paget\u2019s disease of bone"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4029-056X","authenticated-orcid":true,"given":"Xiangxiang","family":"Hu","sequence":"first","affiliation":[{"name":"Oral and Craniofacial Biomedicine Program, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."},{"name":"Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North 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