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Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153

Bone Research 2022年第4期10卷 799-815页

作者： 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 Department of Internal Medicine 3–Rheumatology and Immunology Friedrich Alexander University Erlangen-Nürnberg and Universitätsklinikum ErlangenErlangenGermany Deutsches Zentrum für Immuntherapie Friedrich Alexander University Erlangen-Nuremberg and Universitaetsklinikum ErlangenErlangenGermany Department of Rheumatology Xiangya HospitalCentral South UniversityChangshaHunanChina Core Facility Hohenheim University of HohenheimStuttgartGermany Graduate Institute of Anatomy and Cell biology National Taiwan University College of MedicineTaipeiTaiwan

Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered bone *** 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 *** O-GlcNAcylation is one of the most common protein modifications,its role in bone homeostasis has not been systematically *** demonstrate that dynamic changes in O-GlcNAcylation are required for *** O-GlcNAcylation promotes osteoclast differentiation during the early stages,whereas its downregulation is required for osteoclast *** the molecular level,O-GlcNAcylation affects several pathways including oxidative phosphorylation and cell-cell ***αfosters the dynamic regulation of O-GlcNAcylation to promote osteoclastogenesis in inflammatory *** 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 *** of NUP153,an O-GlcNAcylation target,has similar effects as OGT inhibition and inhibits *** findings highlight an important role of O-GlcNAcylation in osteoclastogenesis and may offer the potential to therapeutically interfere with pathologic bone resorption.

关键词： osteoclast homeostasis maintained

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