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Our previous study demonstrated that the downregulation of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1), a circadian clock protein, inhibited the Wnt\/\u03b2-catenin pathway via enhanced GSK-3\u03b2 in diabetic BMSCs. In this article, we confirmed that the downregulated BMAL1 in T2DM played an inhibitory role in osteogenic differentiation of BMSCs. Upregulation of BMAL1 in the diabetic BMSCs significantly recovered the expression pattern of osteogenic marker genes and alkaline phosphatase (Alp) activity. We also observed an activation of the p53 signaling pathways, exhibited by increased p53 and p21 in diabetic BMSCs. Downregulation of p53 resulting from overexpression of BMAL1 was detected, and when we applied p53 gene silencing (shRNA) and the p53 inhibitor, pifithrin-\u03b1 (PFT-\u03b1), the impaired osteogenic differentiation ability of diabetic BMSCs was greatly restored. However, there was no change in the level of expression of BMAL1. Taken together, our results first revealed that BMAL1 regulated osteogenesis of BMSCs through p53 in T2DM, providing a novel direction for further exploration of the mechanism underlying osteoporosis in diabetes.<\/jats:p>","DOI":"10.1242\/bio.051482","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T13:15:20Z","timestamp":1592399720000},"source":"Crossref","is-referenced-by-count":7,"title":["Downregulated brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 inhibits osteogenesis of BMSCs through p53 in type 2 diabetes mellitus"],"prefix":"10.1242","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-0520","authenticated-orcid":false,"given":"Xiaofei","family":"Mao","sequence":"first","affiliation":[{"name":"Chinese PLA General Hospital 1 Department of Stomatology , , Beijing 100853 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-9452","authenticated-orcid":false,"given":"Xiaoguang","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong University 2 Department of Stomatology , , Jinan, Shandong 250021 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital 1 Department of Stomatology , , Beijing 100853 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwei","family":"Hao","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital 1 Department of Stomatology , , Beijing 100853 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital 1 Department of Stomatology , , Beijing 100853 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Guan","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital 1 Department of Stomatology , , Beijing 100853 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-1815","authenticated-orcid":false,"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"Chinese PLA General Hospital 1 Department of Stomatology , , Beijing 100853 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,7,8]]},"reference":[{"key":"2022062810095756500_BIO051482C1","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1089\/scd.2016.0067","article-title":"Receptor for advanced glycation end products-mediated signaling impairs the maintenance of bone marrow mesenchymal stromal cells in diabetic model mice","volume":"25","author":"Aikawa","year":"2016","journal-title":"Stem Cells Dev."},{"key":"2022062810095756500_BIO051482C2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/obr.12502","article-title":"The circadian clock, metabolism and obesity","volume":"18","author":"Albrecht","year":"2017","journal-title":"Obes. 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