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Aging and menopause reprogram osteoclast precursors for aggressive bone resorption

Bone Research 2020年第3期8卷 333-342页

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 Clinical Cell Biology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Regional Health Research University of Southern Denmark5230 Odense MDenmark Department of Clinical Biochemistry and Immunology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Clinical Cell Biology Department of PathologyOdense University Hospital5000 Odense CDenmark Department of Clinical Research University of Southern Denmark5230 Odense MDenmark Department of Molecular Medicine University of Southern Denmark5230 Odense MDenmark Department of Clinical Genetics Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Oncology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark OPEN Odense Patient data Explorative NetworkOdense University Hospital5000 Odense CDenmark

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 are"reprogrammed"in vivo,allowing them to"remember"age,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.

关键词： osteoclast menopause osteoporosis

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