https://scholars.lib.ntu.edu.tw/handle/123456789/627812
標題: | Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153 | 作者: | 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 MIN-CHUAN HUANG NENG-YU LIN Ramming, Andreas Schett, Georg Distler, Jörg H W |
關鍵字: | N-ACETYLGLUCOSAMINE; TRANSCRIPTION; MICE; PHOSPHORYLATION; IDENTIFICATION; INFLAMMATION; ACTIVATION; EXPRESSION; RANKL; GLYCOSYLATION | 公開日期: | 26-七月-2022 | 出版社: | SPRINGERNATURE | 卷: | 10 | 期: | 1 | 來源出版物: | Bone research | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627812 | ISSN: | 2095-4700 | DOI: | 10.1038/s41413-022-00218-9 |
顯示於: | 解剖學暨細胞生物學科所 |
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