Bone Marrow Stress Decreases Osteogenic Progenitors
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| 024 | 7 | 0 | |a 10.1007/s00223-015-0032-3 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00223-015-0032-3 | ||
| 245 | 0 | 0 | |a Bone Marrow Stress Decreases Osteogenic Progenitors |h [Elektronische Daten] |c [Adeline Ng, Gurpreet Baht, Benjamin Alman, Marc Grynpas] |
| 520 | 3 | |a 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. | |
| 540 | |a Springer Science+Business Media New York, 2015 | ||
| 690 | 7 | |a Aging |2 nationallicence | |
| 690 | 7 | |a Osteogenic progenitors |2 nationallicence | |
| 690 | 7 | |a Mouse model |2 nationallicence | |
| 690 | 7 | |a Bone quality |2 nationallicence | |
| 690 | 7 | |a Osteoblast |2 nationallicence | |
| 700 | 1 | |a Ng |D Adeline |u Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada |4 aut | |
| 700 | 1 | |a Baht |D Gurpreet |u Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada |4 aut | |
| 700 | 1 | |a Alman |D Benjamin |u Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada |4 aut | |
| 700 | 1 | |a Grynpas |D Marc |u Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada |4 aut | |
| 773 | 0 | |t Calcified Tissue International |d Springer US; http://www.springer-ny.com |g 97/5(2015-11-01), 476-486 |x 0171-967X |q 97:5<476 |1 2015 |2 97 |o 223 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00223-015-0032-3 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00223-015-0032-3 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ng |D Adeline |u Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Baht |D Gurpreet |u Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Alman |D Benjamin |u Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Grynpas |D Marc |u Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Calcified Tissue International |d Springer US; http://www.springer-ny.com |g 97/5(2015-11-01), 476-486 |x 0171-967X |q 97:5<476 |1 2015 |2 97 |o 223 | ||