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Among noncoding RNAs, long noncoding RNAs (lncRNAs), which contain hundreds to thousands of bases, have received attention in many fields. The vast majority of the constituent cells in bone tissue are osteocytes, but their regulatory mechanisms are incompletely understood. Considering the wide range of potential contributions of lncRNAs to physiological processes and pathological conditions, we hypothesized that lncRNAs in osteocytes, which have not been reported, could be involved in bone metabolism. Here, we first isolated osteocytes from femurs of mice with osteocyte-specific GFP expression. Then, through RNA-sequencing, we identified osteocyte-specific lncRNAs and focused on a novel lncRNA, 9530026P05Rik (lncRNA953Rik), which strongly suppressed osteogenic differentiation. In the IDG-SW3 osteocyte line with lncRNA953Rik overexpression, the expression of Osterix and its downstream genes was reduced. RNA pull-down and subsequent LC-MS\/MS analysis revealed that lncRNA953Rik bound the nuclear protein CCAR2. We demonstrated that CCAR2 promoted Wnt\/\u03b2-catenin signaling and that lncRNA953Rik inhibited this pathway. lncRNA953Rik sequestered CCAR2 from HDAC1, leading to deacetylation of H3K27 in the Osterix promoter and consequent transcriptional downregulation of Osterix. This research is the first to clarify the role of a lncRNA in osteocytes. Our findings can pave the way for novel therapeutic options targeting lncRNAs in osteocytes to treat bone metabolic diseases such as osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms241713633","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:14:50Z","timestamp":1693793690000},"page":"13633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Novel Long Noncoding RNA in Osteocytes Regulates Bone Formation through the Wnt\/\u03b2-Catenin Signaling Pathway"],"prefix":"10.3390","volume":"24","author":[{"given":"Makoto","family":"Arai","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ochi","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation for Motor Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, Tokorozawa 359-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Sunamura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-5372","authenticated-orcid":false,"given":"Nobuaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo 113-8655, Japan"},{"name":"Osteoporosis Center, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Takeda","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Toranomon Hospital Endocrine Center, Tokyo 105-8470, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6227-5910","authenticated-orcid":false,"given":"Shingo","family":"Sato","sequence":"additional","affiliation":[{"name":"Center for Innovative Cancer Treatment, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1126\/science.1058040","article-title":"The sequence of the human genome","volume":"291","author":"Venter","year":"2001","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"International Human Genome Sequencing Consortium (2004). 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