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REPORT DATE October 2000
REPORT TYPE AND DATES COVEREDAnnual (1 Sep 99 -31 Aug 00)
TITLE AND SUBTITLE
Alcohol and Adaptation to Mechanical Usage
AUTHOR(S)Russell T. Turner, Ph.D.
FUNDING NUMBERS
DAMD17-98-1-8517
PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Mayo Foundation Rochester, Minnesota 55905 E-MAIL: rolbiecki.lori@mayo.edu These studies are designed to determine whether ethanol antagonizes the ability of the skeleton to adapt to increased mechanical usage. Ethanol reversibly alters the biophysical properties of cell membranes.The overall hypothesis to be tested in adult rats is that these membrane changes disrupt essential cell signaling pathways for one or more cytokines, growth factors and polypeptide hormones that regulate bone modeling and remodeling.This report summarizes our progress from 01 September 1999 to 31 August 2000. During Year 2 of the award we have continued analysis of experiments performed in Year 1 related to Tasks 1-4 and 8.Additional experiments were performed to accomplish Task 8. Progress was also made on Tasks 6, 7, and 8.The new studies are directed toward determination of the effects of ethanol on: the skeletal readaptation to normal weight bearing following unloading (Task 6), skeletal adaptation to treadmill running (Task 7), PTH-induced increases in mRNA levels for bone matrix proteins (Task 8), and PTH-induced increases in osteoblast number and bone formation (Task 9).
SUBJECT TERMS Neurotoxin
NUMBER OF PAGES
INTRODUCTIONChronic alcohol abuse is an important risk factor for osteoporosis. The ultimate goal of this research is to identify the cellular and molecular mechanisms responsible for mediating ethanol's dose-and time-dependent actions on bone turnover, mass, architecture, and strength. It is well established that ethanol reversibly alters the biophysical properties of cell membranes and in doing so disturbs normal membrane function. The proposed studies in young adult rats will test our working hypothesis that these membrane changes disrupt essential cell signaling pathways for one or more bone cells "coupling" factors and/or polypeptide hormones that regulate bone modeling and remodeling. These changes are postulated to lead to the bone loss associated with chronic alcohol abuse. If our hypothesis is correct, then ethanol antagonizes the ability of t...