Bone Marrow Stress Decreases Osteogenic Progenitors

摘要: Age-related bone loss may be a result of declining levels stem cells in the marrow. Using Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as source marrow stress order to investigate effects aging on osteogenic progenitors which reside space. Five-month-old DTK mice were treated with one or two cycles ganciclovir conditionally ablate differentiated osteoblasts, whereas controls saline-treated. Treatment weeks length followed by four recovery. All animals sacrificed at 8 months age; stromal (BMSCs) harvested for cell culture and whole bones excised quality assessment. Colony-forming unit (CFU) assays conducted potential BMSC vitro, RNA extracted assess expression osteoblastic genes. Bone assessments included histomorphometry, TRAP staining, microcomputed tomography, biomechanical testing. Osteoblast decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), CFU-VK (von Kossa) counts capacity culture. Ex vivo, there no differences mineral density vertebrae femurs between treatment groups. Histology showed decrease volume connectivity repeated depletion; however, this accompanied an increase formation rate. There notable osteoclast parameters observed adiposity. We have developed model that uses mimic age-related progenitors. Our data suggest number healthy BMSCs their decline depletion. However, activity remaining osteoblasts increases compensate progenitor potential.