{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:56:47Z","timestamp":1792375007205,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to probe into the effect of TRIM33 on oxidative stress\u2010induced apoptosis of osteoblasts in osteoporosis and to probe into the underlying mechanism. The apoptosis of osteoblasts was induced by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> treatment and tested by flow cytometry. A mouse osteoporosis model was conducted by ovariectomy (OVX). The function of TRIM33 was assessed by <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments. The mechanism of TRIM33 was determined by immunoprecipitation, immunofluorescent staining and co\u2010transfection experiments. Here, we found that TRIM33 expression was lessened in the osteoblasts of patients with osteoporosis and was positively correlated with the bone mineral density of these patients. FOXO3a and TRIM33 were co\u2010localized in the osteoblasts nuclei. TRIM33 silence boosted FOXO3a degradation in normal osteoblasts, while TRIM33 overexpression restrained FOXO3a degradation in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated osteoblasts. The binding of TRIM33 to CBP and its overexpression restrained CBP\u2010mediated FOXO3a acetylation, thereby attenuating FOXO3a ubiquitylation. The H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced apoptosis of osteoblasts was restrained by TRIM33 overexpression, while the FOXO3a knockdown reversed this trend. The <jats:italic>in vivo<\/jats:italic> experiments corroborated that TRIM33 overexpression attenuated the OVX\u2010driven impacts in mice. In general, our findings expounded that TRIM33 protected osteoblasts against oxidative stress\u2010induced apoptosis in osteoporosis and that the underlying mechanism was the restraint of FOXO3a ubiquitylation and degradation.<\/jats:p>","DOI":"10.1111\/acel.13367","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T09:38:29Z","timestamp":1623231509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["TRIM33 protects osteoblasts from oxidative stress\u2010induced apoptosis in osteoporosis by inhibiting FOXO3a ubiquitylation and degradation"],"prefix":"10.1111","volume":"20","author":[{"given":"De\u2010bo","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Shandong First Medical University Jinan, Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyou","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Dezhou People\u2019s Hospital Dezhou, Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Qilu Hospital of Shandong University Jinan, Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2213-2851","authenticated-orcid":false,"given":"Haichun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Qilu Hospital of Shandong University Jinan, Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.12.009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45213"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-010-9393-9"},{"issue":"5","key":"e_1_2_8_5_1","first-page":"3685","article-title":"Prognostic role of Tif1gamma expression and circulating tumor cells in patients with breast cancer","volume":"19","author":"Cai F. 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