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Accession Number:
ADA581691
Title:
Advancing Individualized Medicine by Understanding Phenotypic Integration Using the Human Skeleton as a Model System
Descriptive Note:
Annual rept. 1 Sep 2010-31 Aug 2011
Corporate Author:
MOUNT SINAI MEDICAL CENTER OF THE CITY OF NEW YORK
Report Date:
2011-09-01
Pagination or Media Count:
86.0
Abstract:
Susceptibility to common, heritable diseases is generally thought to originate at the genetic-level, and most studies seek genomic variants or altered molecular networks to develop novel diagnostics and treatments to reduce disease risk on a personalized basis. We show that fracture susceptibility in human tibiae and femora can also arise at a higher-level of biological organization, a phenomenon that may be difficult to predict from genetic information alone, because it involved biomechanical tradeoffs, constraints on cellular activity, and a network of compensatory trait interactions defining organ-level function. Importantly, we also identified a novel level of biological control regulating the degree of internal remodeling affecting young adult tibiae and aging femora. Limited compensation at this level of biological organization may be a public health concern, not only because of the increased fracture susceptibility, but also because it is unclear to what extent prophylactic treatments can circumvent intrinsic cellular constraints to establish a higher degree of functional equivalence among individuals. Thus, the funds supporting our research efforts have significantly advanced our understanding of bone by identifying a flaw or limitation in the functional adaptation process that may contribute to fracture risk and by discovering biological controls regulating internal remodeling that have not previously been reported.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
