Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

作     者：Morten S.Hansen Kaja Madsen Maria Price Kent Søe Yasunori Omata Mario M.Zaiss Caroline M.Gorvin Morten Frost Alexander Rauch Morten S.Hansen;Kaja Madsen;Maria Price;Kent Søe;Yasunori Omata;Mario M.Zaiss;Caroline M.Gorvin;Morten Frost;Alexander Rauch

作者机构：Molecular Endocrinology Laboratory(KMEB)Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical ResearchFaculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell BiologyPathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and Systems Research(IMSR)and Centre for DiabetesEndocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for Membrane Proteins and Receptors(COMPARE)Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular MedicineUniversity of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic SurgeryFaculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI)Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany Steno Diabetes Center OdenseOdense University HospitalDK-5000 Odense CDenmark 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2024年第12卷第1期

页      面：180-198页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：funded by grants from the Novo Nordisk Foundation (NNF18OC0052699) (M.S.H.) and NNF18OC0055047 (M.F.) the Region of Southern Denmark (ref: 18/17553 (M.S.H.)) Odense University Hospital (ref: A3147) (M.F.) a faculty fellowship from the University of Southern Denmark (K.M.), the Lundbeck Foundation (ref: R335-2019-2195) (K.M.and A.R.) an Academy of Medical Sciences Springboard Award supported by the British Heart Foundation, Diabetes UK, the Global Challenges Research Fund, the Government Department of Business, Energy and Industrial Strategy and the Wellcome Trust (ref: SBF004 | 1034, C.M.G) a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 224155/Z/21/Z to C.M.G.) 

主　　题：osteoclast programming identif 

摘      要：Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus