Browsing by Person "Ding, Xiao"

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Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153
(2022) Li, Yi-Nan; Chen, Chih-Wei; Trinh-Minh, Thuong; Zhu, Honglin; Matei, Alexandru-Emil; Györfi, Andrea-Hermina; Kuwert, Frederic; Hubel, Philipp; Ding, Xiao; Manh, Cuong Tran; Xu, Xiaohan; Liebel, Christoph; Fedorchenko, Vladyslav; Liang, Ruifang; Huang, Kaiyue; Pfannstiel, Jens; Huang, Min-Chuan; Lin, Neng-Yu; Ramming, Andreas; Schett, Georg; Distler, Jörg H. W.; Li, Yi-Nan; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Chen, Chih-Wei; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Trinh-Minh, Thuong; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Zhu, Honglin; Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, China; Matei, Alexandru-Emil; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Györfi, Andrea-Hermina; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Kuwert, Frederic; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Hubel, Philipp; Core Facility Hohenheim, University of Hohenheim, Stuttgart, Germany; Ding, Xiao; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Manh, Cuong Tran; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Xu, Xiaohan; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Liebel, Christoph; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Fedorchenko, Vladyslav; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Liang, Ruifang; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Huang, Kaiyue; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Pfannstiel, Jens; Core Facility Hohenheim, University of Hohenheim, Stuttgart, Germany; Huang, Min-Chuan; Graduate Institute of Anatomy and Cell biology, National Taiwan University College of Medicine, Taipei, Taiwan; Lin, Neng-Yu; Graduate Institute of Anatomy and Cell biology, National Taiwan University College of Medicine, Taipei, Taiwan; Ramming, Andreas; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Schett, Georg; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany; Distler, Jörg H. W.; Deutsches Zentrum für Immuntherapie, Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum Erlangen, Erlangen, Germany
Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone formation. In inflammatory arthritis such as rheumatoid arthritis (RA), however, increased osteoclast differentiation and activity skew this balance resulting in progressive bone loss. O-GlcNAcylation is a posttranslational modification with attachment of a single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues of target proteins. Although O-GlcNAcylation is one of the most common protein modifications, its role in bone homeostasis has not been systematically investigated. We demonstrate that dynamic changes in O-GlcNAcylation are required for osteoclastogenesis. Increased O-GlcNAcylation promotes osteoclast differentiation during the early stages, whereas its downregulation is required for osteoclast maturation. At the molecular level, O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell fusion. TNFα fosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory arthritis. Targeted pharmaceutical or genetic inhibition of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) arrests osteoclast differentiation during early stages of differentiation and during later maturation, respectively, and ameliorates bone loss in experimental arthritis. Knockdown of NUP153, an O-GlcNAcylation target, has similar effects as OGT inhibition and inhibits osteoclastogenesis. These findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption.