{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:55:32Z","timestamp":1790574932439,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32301088"],"award-info":[{"award-number":["32301088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772409"],"award-info":[{"award-number":["81772409"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010228","name":"Natural Science Foundation of Shaanxi Provincial Department of Education","doi-asserted-by":"publisher","award":["23JK0688"],"award-info":[{"award-number":["23JK0688"]}],"id":[{"id":"10.13039\/501100010228","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bone mechanosensitivity declines with age, resulting in a reduced anabolic response to mechanical stimulation. Although the mechanosensitive ion channel Piezo1 plays a critical role in bone mechanoresponsiveness, its mechanisms of mechanotransduction in aged bone remain incompletely understood. Here, we report that aged tibiae from 19\u2010month\u2010old male mice exhibit a blunted anabolic response to axial cyclic compressive loading or administration of the Piezo1 agonist Yoda1 alone. However, chemical activation of osteocytic Piezo1 by Yoda1 effectively rescues the anabolic response of aged cortical bone to mechanical loading. Mechanistically, Yoda1\u2010induced Piezo1 activation promotes its co\u2010localization with connexin 43 (Cx43) on the osteocyte membrane in response to mechanical stimulation. This Piezo1\u2010Cx43 interaction enhances Cx43 hemichannel (HC) activity via the PI3K\u2010Akt signaling pathway. Subsequent HC opening facilitates the release of the anabolic factor prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) and suppresses the catabolic factor sclerostin (SOST), thereby promoting bone formation and inhibiting bone resorption on the endosteal surface, which ultimately increases cortical bone mass during mechanical loading. Collectively, our findings reveal a mechanism whereby Piezo1 mediates the skeletal anabolic response to mechanical loading in aged bone via Cx43 HCs, offering new perspectives for combating age\u2010related osteoporosis.\n                  <\/jats:p>","DOI":"10.1111\/acel.70687","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:32:11Z","timestamp":1787380331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Piezo1 Activation Rescues Anabolic Response to Mechanical Loading in Aged Bone via Connexin 43 Hemichannels"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-8743","authenticated-orcid":false,"given":"Dezhi","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Medicine Northwest University  Xi'an Shaanxi 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Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine Northwest University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine Northwest University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4873-9934","authenticated-orcid":false,"given":"Huiyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Space Bioscience and Biotechnology, School of Life Science and Technology Northwestern Polytechnical University  Xi'an Shaanxi 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