{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:42:56Z","timestamp":1785868976537,"version":"3.56.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Enhanced osteoclastogenesis causes bone fragility, osteoporosis, and an increased risk of fractures. Recent studies have suggested a possible correlation between osteoporosis and the pathological features of Parkinson's disease (PD). To establish a molecular link between these conditions, we focused on the physiological function of the PD\u2010related protein ubiquitin carboxy\u2010terminal hydrolase L1 (UCHL1) in bone remodeling. To this end, we investigated the role of UCHL1 in regulating osteoclast differentiation in\n                    <jats:italic>Uchl1<\/jats:italic>\n                    spontaneous mutant\n                    <jats:italic>gad<\/jats:italic>\n                    mice. We found that\n                    <jats:italic>gad\u2010<\/jats:italic>\n                    mouse\u2010derived osteoclast progenitors exhibit enhanced osteoclast differentiation. Likewise, CRISPR\u2010mediated\n                    <jats:italic>Uchl1<\/jats:italic>\n                    knockout in mouse macrophage\u2010derived preosteoclast RAW\u2010D cells increased RANKL\u2010dependent osteoclastogenesis. Supporting this observation, these\n                    <jats:italic>Uchl1<\/jats:italic>\n                    \u2010depleted cells showed elevated expression of osteoclast marker genes. To uncover the molecular mechanisms by which the loss of\n                    <jats:italic>Uchl1<\/jats:italic>\n                    enhances osteoclast differentiation, we screened for UCHL1\u2010interacting proteins in RAW\u2010D preosteoclast cells and identified AKT1 as a potential UCHL1\u2010regulated protein. UCHL1 depletion in preosteoclasts led to increased Thr308\/Ser473 phosphorylation of AKT1. Furthermore, ectopic expression of UCHL1 decreased the K63\u2010linked polyubiquitination of AKT1. These findings suggest that UCHL1 is critical in partially suppressing osteoclastogenesis through modulating AKT signaling.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70032","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T11:24:31Z","timestamp":1744629871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of UCHL1 Leads to Enhanced Mouse Osteoclast Formation"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6054-5341","authenticated-orcid":false,"given":"Mitsuki","family":"Chiba","sequence":"first","affiliation":[{"name":"Section of Pediatric Dentistry, Division of Oral Health, Growth and Development Faculty of Dental Science, Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seira","family":"Hoshikawa","sequence":"additional","affiliation":[{"name":"Division of Pediatric Dentistry, Department of Community Social Dentistry Tohoku University Graduate School of Dentistry Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouhei","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Graduate School of Medicine, Osaka Metropolitan University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Degenerative Neurological Diseases National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Degenerative Neurological Diseases National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Yamada","sequence":"additional","affiliation":[{"name":"Section of Pediatric Dentistry, Division of Oral Health, Growth and Development Faculty of Dental Science, Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Pediatric Dentistry, Department of Community Social Dentistry Tohoku University Graduate School of Dentistry Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4892-0047","authenticated-orcid":false,"given":"Hiroyuki","family":"Inuzuka","sequence":"additional","affiliation":[{"name":"Department of Pathology Beth Israel Deaconess Medical Center, Harvard Medical School Boston Massachusetts 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