{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:39:34Z","timestamp":1787827174475,"version":"build-2784847793"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071103"],"award-info":[{"award-number":["82071103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81570958"],"award-info":[{"award-number":["81570958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Young Scientist Program of Beijing Stomatological Hospital","award":["YSP202317"],"award-info":[{"award-number":["YSP202317"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:p>\n                    Mutations in the anoctamin-5 (\n                    <jats:italic>ANO5<\/jats:italic>\n                    ) gene can lead to musculoskeletal disorders, with monoallelic (autosomal dominant) mutations typically presenting as skeletal abnormalities known as gnathodiaphyseal dysplasia (GDD). Clinically, GDD is characterized by thickened cortices of long bones and mandibles, narrowed medullary cavities, and increased bone fragility. While autophagy is necessary in regulating bone formation, the specific relationship between\n                    <jats:italic>ANO5<\/jats:italic>\n                    and autophagy remains poorly understood. In this study, we demonstrated that\n                    <jats:italic>Ano5<\/jats:italic>\n                    deficiency activates autophagy in mouse cranial osteoblasts (mCOBs), leading to enhanced osteogenic capacity in\n                    <jats:italic>\n                      Ano5\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mCOBs. The application of 3-methyladenine (3-MA) and chloroquine (CQ) reversed the excessive osteogenesis observed in\n                    <jats:italic>\n                      Ano5\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mCOBs. Further analysis revealed that\n                    <jats:italic>Ano5<\/jats:italic>\n                    deficiency upregulated the expression of ATG9A, and silencing ATG9A significantly reduced both autophagy and osteogenic activity in\n                    <jats:italic>\n                      Ano5\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mCOBs. Additionally, AMP-activated protein kinase (AMPK) was found to positively regulate ATG9A, and inhibiting AMPK reduced ATG9A expression, which in turn mitigated excessive osteogenesis of\n                    <jats:italic>\n                      Ano5\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mCOBs. Moreover, in vivo experiments confirmed that treatment with 3-MA alleviated the bone phenotype abnormalities in\n                    <jats:italic>\n                      Ano5\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These findings suggest that\n                    <jats:italic>Ano5<\/jats:italic>\n                    negatively regulates autophagy, contributing to illuminate pathogenesis of GDD. Meanwhile, this research highlights potential therapeutic strategies targeting autophagy to pave the way for the clinical manifestations of GDD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.189817","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T12:01:09Z","timestamp":1741694469000},"source":"Crossref","is-referenced-by-count":4,"title":["Anoctamin-5 deficiency enhances ATG9A-dependent autophagy, inducing osteogenesis and gnathodiaphyseal dysplasia\u2013like bone 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