effect of loading status on osteoprogenitors, osteoblasts, chondrocytes and bone formation in the rat
By: by Nick Basso.
Published: 2006
Language: eng
Number of pages: 137
ISBN-13: 9780494157848
Subjects: Theses -- Dentistry.
Description: Skeletal unloading during space flight results in bone loss. In astronauts the extent to which bone is lost varies greatly between different individuals. Because of this, and the limited number of astronauts and cosmonauts to date that have spent long periods of time in space, systematic analysis of this problem in humans is difficult. Experiments with rats flown in space indicate that bone loss is associated with a decrease in bone volume, osteoblast number, and longitudinal bone growth. Since osteoblasts arise from osteoprogenitor cells, we hypothesized that the decrease in osteoblasts and osteoblastic bone formation observed as a result of weightlessness is related to a decrease in the number of osteoprogenitors and/or decreased proliferation of their progeny. Due to the obvious difficulties of performing experiments that utilize space flight, we tested this hypothesis using the NASA developed ground-based rat hind limb unloading model. We evaluated the effect of 14 days of unloading and 14 days of subsequent reloading on osteoprogenitor number (nodules) and alkaline phosphatase positive colonies (CFU-AP) in cell populations derived from the proximal femur of 6 week old rats. To establish whether the effects of unloading were specific for cells of the osteoblast lineage, we also determined the total number of progenitors in the cell populations examined. Bone volume, osteoblast number, and bone formation rate were measured in longitudinal sections of the proximal tibial metaphysis. To determine if unloading had an effect on cartilage growth, we determined the number of apoptotic chondrocytes and measured cartilaginous width in both articular cartilage and in the growth plate. Unloading decreased both nodule number and CFU-AP relative to controls, but had no effect on the total number of progenitors. Bone volume, osteoblast number, and bone formation rate in the proximal tibial metaphysis of unloaded rats were also lower than controls. Subsequent reloading for 14 days restored CFU-AP, however, nodule number was only partially restored. In vivo, osteoblast number and bone formation rate following reloading were also lower than those in corresponding controls. In articular cartilage and in the growth plate, unloading resulted in an increase in apoptotic chondrocytes and a reduction in cartilaginous width. Reloading for 2 weeks was not sufficient for the changes in articular cartilage chondrocytes to return to baseline levels, however some recovery was observed. Chondrocytes in the proliferative and hypertrophic zones of the growth plate responded similarly to those in the articular cartilage. In summary, our results show that the unloading-induced decrease in the number of osteoprogenitors observed in vitro parallels the effects of unloading on bone volume and osteoblast number in vivo, suggesting that the two may be interdependent. (Abstract shortened by UMI.)
Notes: Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 2914.

Thesis (Ph.D.)--University of Toronto, 2006.

Includes bibliographic references.

Electronic version licensed for access by U. of T. users.