caa a22 4500 605520828 CHVBK 20210128100737.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00223-015-0032-3 doi (NATIONALLICENCE)springer-10.1007/s00223-015-0032-3 Bone Marrow Stress Decreases Osteogenic Progenitors [Elektronische Daten] [Adeline Ng, Gurpreet Baht, Benjamin Alman, Marc Grynpas] Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of agingon osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. Springer Science+Business Media New York, 2015 Aging nationallicence Osteogenic progenitors nationallicence Mouse model nationallicence Bone quality nationallicence Osteoblast nationallicence Ng Adeline Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada aut Baht Gurpreet Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada aut Alman Benjamin Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada aut Grynpas Marc Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/5(2015-11-01), 476-486 0171-967X 97:5<476 2015 97 223 https://doi.org/10.1007/s00223-015-0032-3 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/s00223-015-0032-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ng Adeline Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Baht Gurpreet Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Alman Benjamin Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Grynpas Marc Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/5(2015-11-01), 476-486 0171-967X 97:5<476 2015 97 223