caa a22 4500 605520941 CHVBK 20210128100737.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00223-015-9994-4 doi (NATIONALLICENCE)springer-10.1007/s00223-015-9994-4 Deletion of Filamin A in Monocytes Protects Cortical and Trabecular Bone from Post-menopausal Changes in Bone Microarchitecture [Elektronische Daten] [S. Goldberg, J. Glogauer, M. Grynpas, M. Glogauer] The objective of the study was to determine the in vivo role of Filamin A (FLNA) in osteoclast generation and function, through the assessment of trabecular bone morphology, bone turnover, and the resulting changes in mechanical properties of the skeleton in mice with targeted deletion of FLNA in pre-osteoclasts. Using a conditional targeted knockdown of FLNA in osteoclasts, we assessed bone characteristics in vivo including micro-computed tomography (micro-ct), histomorphometric analyses, and bone mechanical properties. These parameters were assessed in female mice at 5months of age, in an aging protocol (comparing 5-month-old and 11-month-old mice) and an osteoporosis protocol [ovariectomized (OVX) at 5months of age and then sacrificed at 6 and 11months of age]. In vivo bone densitometry, mechanical and histomorphometric analyses revealed a mild osteoporotic phenotype in the FLNA-null 5-month and aging groups. The WT and FLNA-KO bones did not appear to age differently. However, the volumetric bone mineral density decrease associated with OVX in WT is absent in FLNA-KO-OVX groups. The skeleton in the FLNA-KO-OVX group does not differ from the FLNA-KO group both in mechanical and structural properties as shown by mechanical testing of femora and vertebrae and histomorphometry of vertebrae. Additionally, FLNA-KO femora are tougher and more ductile than WT femora. The result of this study indicates that while FLNA-KO bones are weaker than WT bones, they do not age differently and are protected from estrogen-mediated post-menopausal osteoporosis. Springer Science+Business Media New York, 2015 FLNA nationallicence Bone turnover nationallicence Osteoporosis nationallicence Aging nationallicence Goldberg S. Matrix Dynamics Group- Faculty of Dentistry, Fitzgerald Building 150 College Street, M5S3E2, Toronto, ON, Canada aut Glogauer J. Matrix Dynamics Group- Faculty of Dentistry, Fitzgerald Building 150 College Street, M5S3E2, Toronto, ON, Canada aut Grynpas M. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Ave, M5G1X5, Toronto, ON, Canada aut Glogauer M. Matrix Dynamics Group- Faculty of Dentistry, Fitzgerald Building 150 College Street, M5S3E2, Toronto, ON, Canada aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/2(2015-08-01), 113-124 0171-967X 97:2<113 2015 97 223 https://doi.org/10.1007/s00223-015-9994-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-9994-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Goldberg S. Matrix Dynamics Group- Faculty of Dentistry, Fitzgerald Building 150 College Street, M5S3E2, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Glogauer J. Matrix Dynamics Group- Faculty of Dentistry, Fitzgerald Building 150 College Street, M5S3E2, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Grynpas M. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Ave, M5G1X5, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Glogauer M. Matrix Dynamics Group- Faculty of Dentistry, Fitzgerald Building 150 College Street, M5S3E2, Toronto, ON, Canada aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/2(2015-08-01), 113-124 0171-967X 97:2<113 2015 97 223