Accession Number : ADA535566


Title :   Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density


Descriptive Note : Final rept.


Corporate Author : LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION REDLANDS CA


Personal Author(s) : Mohan, Subburaman


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a535566.pdf


Report Date : Nov 2010


Pagination or Media Count : 362


Abstract : Our studies address the medical problem of stress fractures in the military as stress fractures are one of the most common and potentially debilitating overuse injuries experienced in the military recruit population. The overall hypothesis that we are addressing in this study is that state of the art molecular genetic approaches can identify the genes and their pathways responsible for extreme differences in skeletal anabolic response to mechanical strain. During the funding period, we have used state-of-the-art technologies to identify the genetic components that contribute to the extreme differences in the skeletal anabolic response to mechanical strain in two inbred strains of mice. The candidate genes identified using QTL and whole genome microarray approaches were then validated using siRNA technique in vitro to suppress expression of genes and evaluating biological response to fluid flow shear strain and targeted or conditional disruption of gene of interest in vivo and evaluating skeletal anabolic response to mechanical loading. Our QTL and whole genome microarray studies revealed that several genetic loci in different chromosomes contribute to the variation in skeletal anabolic response to loading in C57BL/6J (B6) and C3H/HeJ strains of mice. In vitro and in vivo approaches utilizing targeted disruption of genes have identified involvement of IGF-I, integrin and BMP signaling pathways in mechanical loading process. Future validation of mechanosensitive genes in genetic association studies will determine their utility to develop genetic screens to identify individuals who are at increased risk of stress fractures.


Descriptors :   *BONES , *GENETICS , STRAINS(BIOLOGY) , HIGH DENSITY , BONE FRACTURES , RECRUITS , CHROMOSOMES , MILITARY PERSONNEL , GENES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE