This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ligament structure alters with changes in loading conditions. However, little is known regarding the mechanism by which mature ligaments respond to alterations in their local loading environment and subsequently remodel their structure. The goal of this exploratory investigation is to analyze genome-wide changes in fibroblast gene-expression in the rat lateral collateral ligament (LCL) in response to chronic, increased loading. An Affymetrix GeneChip Array will be used to identify genes and mechanisms involved in remodeling of ligament in response to chronic-altered loading conditions. Male, Sprague-Dawley rats, 9 months in age will randomly be assigned to a High Load or Sham group. A mechanical, varus-loading device (VLD) will be surgically attached to one hindlimb of each rat. Animals will be loaded daily for 12-wks. The VLD applies a varus moment of known magnitude to the knee while allowing normal joint function. This causes a quantifiable increase in strain in the LCL. Following the loading, LCLs from the experimental legs will be excised, total RNA extracted, purified, and DNase-treated. Total RNA will be amplified and hybridized to an Affymetrix Rat GeneArray 1.0 ST Array. Statistical analyses will be conducted to compare gene expression levels between LCL mRNA in High Load and Sham groups.
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