{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:53:57Z","timestamp":1772160837842,"version":"3.50.1"},"reference-count":71,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to investigate the effect of endoplasmic reticulum (ER) stress sensor inositol\u2010requiring enzyme 1\u03b1 (IRE1\u03b1) on the sonic hedgehog N\u2010terminus (N\u2010Shh)\u2010enhanced\u2010osteogenic differentiation process in mouse embryonic fibroblasts (MEFs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Osteogenesis of MEFs was observed by alkaline phosphatase (ALP) staining, alizarin red staining, and Von Kossa staining assays. Activation of unfolded protein response and Shh signaling were examined using real\u2010time quantitative PCR and western blot assays. IRE1\u03b1\u2010deficient MEFs were used to explore the effect of IRE1\u03b1 on N\u2010Shh\u2010driven osteogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      N\u2010Shh increased ALP activity, matrix mineralization, and the expression of\n                      <jats:italic>Alp<\/jats:italic>\n                      and\n                      <jats:italic>Col\u2010I<\/jats:italic>\n                      in MEFs under osteogenic conditions; notably, this was reversed when combined with the ER stress activator Tm treatment. Interestingly, the administration of N\u2010Shh decreased the expression of IRE1\u03b1. Abrogation of IRE1\u03b1 increased the expression of Shh pathway factors in osteogenesis\u2010induced MEFs, contributing to the osteogenic effect of N\u2010Shh. Moreover, IRE1\u03b1\u2010deficient MEFs exhibited elevated levels of osteogenic markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that the IRE1\u03b1\u2010mediated unfolded protein response may alleviate the ossification of MEFs by attenuating Shh signaling. Our research has identified a strategy to inhibit excessive ossification, which may have clinical significance in preventing temporomandibular joint bony ankylosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.14919","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T22:41:11Z","timestamp":1709592071000},"page":"4504-4517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>IRE1\u03b1<\/scp>\n                    inhibits osteogenic differentiation of mouse embryonic fibroblasts by limiting Shh signaling"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6891-2751","authenticated-orcid":false,"given":"Zhixiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Stomatology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"},{"name":"Department of 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