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Article
2022
Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153
Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153
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.
Abstract (English)
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.
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Bone research, 10 (2022), 1, 51.
https://doi.org/10.1038/s41413-022-00218-9.
ISSN: 2095-6231
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English
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610 Medicine and health
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@article{Li2022-07-26,
doi = {10.1038/s41413-022-00218-9},
author = {Li, Yi-Nan and Chen, Chih-Wei and Trinh-Minh, Thuong et al.},
title = {Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153},
journal = {Bone Research},
year = {2022-07-26},
volume = {10},
number = {1},
}