OGT mediates O-GlcNAcylation of MEIS2 and affects palatal osteogenic developmentOA
Post-translational modifications(PTMs)have been gradually elucidated in congenital malformations such as cleft palate.Among them,O-GlcNAcylation as a dynamic PTM of proteins regulates various critical biological processes including transcription,translation,and cell fate determination.In this study,a substantial decline in O-linked β-D-N-acetylglucosamine(O-GlcNAc)levels was detected within the palatine plates of all-trans retinoic acid(atRA)-induced cleft palate mice.The role of O-GlcNAc transferase(OGT),the sole enzyme responsible for catalyzing O-GlcNAcylation,was investigated in the process of palatal development.In a zebrafish model,the loss of O-GlcNAc resulted in an elevated prevalence of cleft palate and compromised palatal bone formation.Mechanistically,O-GlcNAcylation of myeloid ecotropic viral integration site 2(MEIS2),which is mediated by OGT,was found to maintain osteogenic homeostasis by modulating its protein stability through inhibition of ubiquitination.Notably,the serine 237 residue(Ser237)was identified as a critical site for MEIS2 O-GlcNAcylation.Together,the present study uncovers the important function of MEIS2 O-GlcNAcylation in palatal bone development and establishes a novel theoretical framework for understanding the regulatory network of palatal development.This finding may provide novel avenues for the future diagnosis and prevention of cleft palate.
Zhongyin Zhang;Zerui Shan;Xinyu Chen;Yu Xia;Li Meng;Yuxin Zhang;Caihong Wu;Lichan Yuan;Junqing Ma
Department of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Prosthodontics,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,College of Stomatology,Shanghai Jiao Tong University,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai Key Laboratory of Stomatology,Shanghai Engineering Research Center of Advanced Dental Technology and Materials,Shanghai,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,ChinaDepartment of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing,China State Key Laboratory Cultivation Base of Research,Prevention and Treatment for Oral Diseases,Nanjing Medical University,Nanjing,China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing,China Savaid Stomatology School,Hangzhou Medical College,Hangzhou,China Hangzhou Stomatological Hospital(Zijingang Campus),Hangzhou,China
医药卫生
O linked N AcetylglucosamineO GlcNAcylationPalatal DevelopmentMeispalatine platescleft palateamongcleft palatecongenital malformations
《International Journal of Oral Science》 2026 (3)
P.533-546,14
supported by the National Natural Science Foundation of China(82201002,82501088)China Postdoctoral Science Foundation(2024M751493)Seeking Truth Talent Project of Hangzhou Medical College。
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