Weidong Geng

Date of Award

2000

Degree Name

Biomedical Sciences

College

Joan C. Edwards School of Medicine

Type of Degree

Ph.D.

Document Type

Dissertation

First Advisor

Patrick I. Brown

Second Advisor

Beverly Delidow

Third Advisor

William D. McCumbee

Fourth Advisor

Michael Norton

Fifth Advisor

Gary L. Wright

Sixth Advisor

Leonard J. Deutsch

Abstract

In order to determine the strategies in regulation of bone mass in the rat and better understand the pathophysiological mechanism of the postmenopausal osteoporosis, a series of studies were conducted at the whole animal and cellular level. At the whole animal level, female Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated (control) at 18 weeks and the entire skeleton obtained at 24 weeks (baseline) or after an additional 31 day (28 week) interval on a normal (1.0%) or deficient (0.02%) calcium diet. Ovx rats on the normal calcium diet showed a 42% increase in whole body bone resorption and a 70% increase in resorption with morphological evidence of dramatic loss of cancellous bone mass when placed on calcium-deficient diets. The total skeleton mass of these animals, however, was significantly reduced (-20%) from that predicted by calculations based on body weight. Calcium-deficient diets had no significant effect on total bone mass. It was determined; however, that dietary calcium deficiency caused decreased skeletal growth of the axial skeleton but not the appendicular skeletons. The results suggest that ovariectomy or dietary calcium deficiency did not induce an overt loss of total bone mass but might involve a redistribution of bone mass. At the cellular level, osteoblastic UMR-108 cells showed a dramatic orientation response to mechanical stress (cyclic stretching) with cell reshaping and alignment of the cell long axis perpendicular to the axis of force, remodeling of the actin cytoskeleton, and the appearance of multiple focal adhesions staining for actin, vinculin, and PKC. Longer-term mechanical stress beyond 24 hours, however, resulted in no significant change in the mRNA level, protein level of the PKC-α, -e, -e. The results indicate that PKC could be involved in the early phase of mechanotransduction in osteoblasts through the activation of focal adhesion assembly/disassembly and the remodeling of the actin cytoskeleton.

Subject(s)

Calcium in the body.

Bones – Pathophysiology.

Osteoporosis – Research.

Download

Share

COinS