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1篇 您的检索式:作者名="Frederic Kuwert"
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1Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153显示文摘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-linkedβ-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.TNFαfosters 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.Yi-Nan Li Chih-Wei Chen Thuong Trinh-Minh Honglin Zhu Alexandru-Emil Matei Andrea-Hermina Györfi Frederic Kuwert Philipp Hubel Xiao Ding Cuong Tran Manh Xiaohan Xu Christoph Liebel Vladyslav Fedorchenko Ruifang Liang Kaiyue Huang Jens Pfannstiel Min-Chuan Huang Neng-Yu Lin Andreas Ramming Georg Schett Jörg H.W.Distler 2022Bone Research2022,10,4:1
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