Aging and menopause reprogram osteoclast precursors for aggressive bone resorption

作     者：Anais Marie Julie Moller Jean-Marie Delaisse Jacob Bastholm Olesen Jonna Skov Madsen Luisa Matos Canto Troels Bechmann Silvia Regina Rogatto Kent Soe Ana?s Marie Julie M?ller;Jean-Marie Delaissé;Jacob Bastholm Olesen;Jonna Skov Madsen;Luisa Matos Canto;Troels Bechmann;Silvia Regina Rogatto;Kent S?e

作者机构：Clinical Cell BiologyLillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Regional Health ResearchUniversity of Southern Denmark5230 Odense MDenmark Department of Clinical Biochemistry and ImmunologyLillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Clinical Cell BiologyDepartment of PathologyOdense University Hospital5000 Odense CDenmark Department of Clinical ResearchUniversity of Southern Denmark5230 Odense MDenmark Department of Molecular MedicineUniversity of Southern Denmark5230 Odense MDenmark Department of Clinical GeneticsLillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of OncologyLillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark OPENOdense Patient data Explorative NetworkOdense University Hospital5000 Odense CDenmark 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2020年第8卷第3期

页      面：333-342页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：This study was financed by the Research Counsel of Lillebaelt Hospital the Region of Southern Denmark(15/24819) the Institute of Regional Health Research,University of Southern Denmark the Aase Ejnar Danielsen foundation(10-001835) the Fru Astrid Thaysens foundation(ATL 16/02) We particularly wish to thank Annette Ulv for her hard work recruiting the blood donors,Merete Villumsen for her excellent technical assistance on CTX and PINP measurements,and Hellen Kuasne for her kind support in primer selection for pyrosequencing 

主　　题：osteoclast menopause osteoporosis 

摘      要：Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing *** increased osteoclast activity has been linked to a reduced estrogen level and other hormonal ***,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast ***,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were *** multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with *** conclude that monocytes arereprogrammedin vivo,allowing them torememberage,the menopausal status,and the bone formation status in vitro,resulting in more aggressive *** discovery suggests that this may be mediated through DNA *** suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.