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The repair and regeneration of large bone defects represent highly challenging tasks in bone tissue engineering. Although recent studies have shown that osteogenesis is stimulated by periodic heat stress, the thermal regulation of osteogenic differentiation in ectomesenchymal stem cells (EMSCs) is not well studied. Methods and Results. In this study, the direct effects of periodic heat stress on the differentiation of EMSCs into osteoblasts were investigated. EMSCs derived from rat nasal respiratory mucosa were seeded onto culture plates, followed by 1\u2009h of heat stress at 41\u00b0C every 7 days during osteogenic differentiation. Based on the results of the present study, periodic heating increases alkaline phosphatase (ALP) activity, upregulates osteogenic-related proteins, and promotes EMSC mineralization. In particular, increased YAP nuclear translocation and YAP knockdown inhibited osteogenic differentiation induced by heat stress. Furthermore, the expression and activity of transglutaminase 2 (TG2) were significantly increased after YAP nuclear translocation. Conclusion. Together, these results indicate that YAP plays a key role in regulating cellular proteostasis under stressful cellular conditions by modulating the TG2 response.<\/jats:p>","DOI":"10.1155\/2022\/3715471","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T16:52:00Z","timestamp":1647622320000},"page":"1-14","source":"Crossref","is-referenced-by-count":13,"title":["Periodic Heat Stress Licenses EMSC Differentiation into Osteoblasts via YAP Signaling Pathway Activation"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-5850","authenticated-orcid":true,"given":"Wentao","family":"Shi","sequence":"first","affiliation":[{"name":"Jiangnan University Affiliated Hospital, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Bian","sequence":"additional","affiliation":[{"name":"Jiangnan University Affiliated Hospital, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Jiangnan University Affiliated Hospital, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"HuiYa","sequence":"additional","affiliation":[{"name":"Jiangnan University Affiliated Hospital, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Affiliated Wuxi Second Hospital, Nanjing Medical University, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-7914","authenticated-orcid":true,"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6990-1363","authenticated-orcid":true,"given":"Xiaojie","family":"Lu","sequence":"additional","affiliation":[{"name":"Jiangnan University Affiliated Hospital, Wuxi, Jiangsu Province 214122, China"},{"name":"School of Medicine, Jiangnan University, Wuxi, Jiangsu Province 214122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06504-7"},{"issue":"1","key":"2","first-page":"1406","article-title":"Local transplantation of osteogenic pre-differentiated autologous adipose-derived mesenchymal stem cells may accelerate non-union fracture healing with limited pro-metastatic potency","volume":"8","author":"D. 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