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The role of O-GlcNAcylation mediated by OGT during tooth development

Authors
 Elina Pokharel  ;  Yam P Aryal  ;  Tae-Young Kim  ;  Anna Kim  ;  Jae-Kwang Jung  ;  Seo-Young An  ;  Tae-Yub Kwon  ;  Bong-Ki Min  ;  Hitoshi Yamamoto  ;  Sung-Won Cho  ;  Wern-Joo Sohn  ;  Chang-Hyeon An  ;  Youngkyun Lee  ;  Do-Yeon Kim  ;  Jung-Hong Ha  ;  Jae-Young Kim 
Citation
 JOURNAL OF CELLULAR PHYSIOLOGY, Vol.238(7) : 1520-1529, 2023-07 
Journal Title
JOURNAL OF CELLULAR PHYSIOLOGY
ISSN
 0021-9541 
Issue Date
2023-07
MeSH
Animals ; Apoptosis / physiology ; Hedgehog Proteins / genetics ; Hedgehog Proteins / metabolism ; Mice ; N-Acetylglucosaminyltransferases* / genetics ; N-Acetylglucosaminyltransferases* / metabolism ; Protein Processing, Post-Translational ; Tooth* / growth & development ; Tooth* / metabolism
Keywords
OSMI-1 ; dental hard tissue formation ; posttranslational modification ; signaling regulation ; tooth morphogenesis
Abstract
To understand the mechanisms underlying tooth morphogenesis, we examined the developmental roles of important posttranslational modification, O-GlcNAcylation, which regulates protein stability and activity by the addition and removal of a single sugar (O-GlcNAc) to the serine or threonine residue of the intracellular proteins. Tissue and developmental stage-specific immunostaining results against O-GlcNAc and O-GlcNAc transferase (OGT) in developing tooth germs would suggest that O-GlcNAcylation is involved in tooth morphogenesis, particularly in the cap and secretory stage. To evaluate the developmental function of OGT-mediated O-GlcNAcylation, we employed an in vitro tooth germ culture method at E14.5, cap stage before secretory stage, for 1 and 2 days, with or without OSMI-1, a small molecule OGT inhibitor. To examine the mineralization levels and morphological changes, we performed renal capsule transplantation for one and three weeks after 2 days of in vitro culture at E14.5 with OSMI-1 treatment. After OGT inhibition, morphological and molecular alterations were examined using histology, immunohistochemistry, real-time quantitative polymerase chain reaction, in situ hybridization, scanning electron microscopy, and ground sectioning. Overall, inhibition of OGT resulted in altered cellular physiology, including proliferation, apoptosis, and epithelial rearrangements, with significant changes in the expression patterns of beta-catenin, fibroblast growth factor 4 (fgf4), and sonic hedgehog (Shh). Moreover, renal capsule transplantation and immunolocalizations of Amelogenin and Nestin results revealed that OGT-inhibited tooth germs at cap stage exhibited with structural changes in cuspal morphogenesis, amelogenesis, and dentinogenesis of the mineralized tooth. Overall, we suggest that OGT-mediated O-GlcNAcylation regulates cell signaling and physiology in primary enamel knot during tooth development, thus playing an important role in mouse molar morphogenesis.
Full Text
https://onlinelibrary.wiley.com/doi/10.1002/jcp.31024
DOI
10.1002/jcp.31024
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Cho, Sung Won(조성원) ORCID logo https://orcid.org/0000-0001-7505-9769
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/199495
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