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IRE1α inhibits osteogenic differentiation of mouse embryonic fibroblasts by limiting Shh signaling

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单位： [1]Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [2]Department of Prosthodontics and Implantology, School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [3]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, Hubei, China. [4]Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, and the Institute for Advanced Studies, Wuhan University, Wuhan, Hubei, China. [5]Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, Huazhong University of Science and Technology, Wuhan, Hubei, China.

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关键词： ER stress IRE1α mouse embryonic fibroblasts osteogenesis sonic hedgehog

摘要：

This study aimed to investigate the effect of endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α) on the sonic hedgehog N-terminus (N-Shh)-enhanced-osteogenic differentiation process in mouse embryonic fibroblasts (MEFs).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-time quantitative PCR and western blot assays. IRE1α-deficient MEFs were used to explore the effect of IRE1α on N-Shh-driven osteogenesis.N-Shh increased ALP activity, matrix mineralization, and the expression of Alp and Col-I in MEFs under osteogenic conditions; notably, this was reversed when combined with the ER stress activator Tm treatment. Interestingly, the administration of N-Shh decreased the expression of IRE1α. Abrogation of IRE1α increased the expression of Shh pathway factors in osteogenesis-induced MEFs, contributing to the osteogenic effect of N-Shh. Moreover, IRE1α-deficient MEFs exhibited elevated levels of osteogenic markers.Our findings suggest that the IRE1α-mediated 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.© 2024 Wiley Periodicals LLC.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 4 区牙科与口腔外科

最新[2025]版：

大类 | 3 区医学

小类 | 4 区牙科与口腔外科

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出版当年[2022]版：

Q1 DENTISTRY, ORAL SURGERY & MEDICINE

最新[2023]版：

Q1 DENTISTRY, ORAL SURGERY & MEDICINE

影响因子： 2.9 最新[2023版] 3.4 最新五年平均 3.8 出版当年[2022版] 3.6 出版当年五年平均 4.068 出版前一年[2021版] 2.9 出版后一年[2023版]

第一作者：

第一作者单位： [1]Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [2]Department of Prosthodontics and Implantology, School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [3]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, Hubei, China.

通讯作者：

通讯机构： [1]Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [2]Department of Prosthodontics and Implantology, School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [3]Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, Hubei, China.

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IRE1α inhibits osteogenic differentiation of mouse embryonic fibroblasts by limiting Shh signaling

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