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HINDLIMB UNLOADING RESULTS IN A DECREASE IN FEMORAL OSTEOPROGENITOR CELL NUMBER IN THE YOUNG MALE RAT.  N. Basso, Y. Jia, C.G. Bellows and J.N.M. Heersche.  Faculty of Dentistry, University of Toronto, Toronto.

     We hypothesize that the reduction in bone mineral density observed in humans and rats following space flight or mechanical unloading is primarily caused by a sustained disruption in the development of cells of the osteoblast lineage. Using the NASA model of tail suspension, we investigated changes in fibroblastic colony forming units (CFU-F), alkaline phosphatase positive CFUs (CFU-AP) and osteoprogenitors (CFU-O) in cells isolated from the proximal femur, calvarium and proximal humerus in six-week old male Fischer rats hindlimb unloaded (HU) for 14 days. The proximal tibia was used for histomorphometric and in situ hybridization evaluation of changes in bone formation parameters. Normally loaded control rats were pair-fed. Cells were obtained from explant cultures and cultured for either 15 or 21 days in the presence or absence of 10 nM dexamethasone. There was no significant difference in the number of CFU-F between cell populations derived from HU and control rats for any of the 3 bone sites evaluated (n=3). With respect to CFU-AP, we observed a 31% decrease (n=3, p<0.01) in cells isolated from femur and a 2-fold increase (n=3, p<0.01) in cells isolated from the calvaria of HU rats. We also observed a 61% decrease (n=3, p<0.01) in CFU-O in cells isolated from femur, and a 1.3 fold increase (n=3, p<0.01) in cells isolated from calvaria of HU rats. CFU-AP and CFU-O were not significantly different in cells isolated from humerus from either group (n=3). Preliminary histomorphometric and in situ hybridization analysis performed on the proximal tibia indicates that the major difference in HU rats is a decrease in trabecular bone volume, mainly reflecting a decrease in primary spongiosa, and a decrease in collagen mRNA content.  In conclusion, cell culture studies illustrate that the number of osteoprogenitors and therefore osteogenic potential is decreased in cells isolated from the proximal femur and is increased in cells isolated from calvarium as a result of HU.