Presentation Abstract

Session: 376-390-Pediatrics III
Date/Time: Thursday, Mar 13, 2014, 9:18 AM - 9:24 AM
Location Room 245
Presentation Number: Paper 386
Title: Gene Expression Differences in Young Male and Female Ruptured Anterior Cruciate Ligaments
Classification: +Knee (Pediatrics)
Keywords: Knee; ACL Deficient
Author(s): Susan M. Moen, MD, Akron, Ohio
Jeffrey S. Johnson, MD, Rock Springs, Wyoming
Robin Jacquet, Akron, Ohio
Melanie Morscher, Akron, Ohio
Christopher J. Klonk, Akron, Ohio
Kerwyn Jones, MD, Akron, Ohio
William J. Landis, Akron, Ohio
Abstract: INTRODUCTION: There is a two- to eight-fold greater incidence of anterior cruciate ligament (ACL) injuries among female athletes compared to males. Anatomic, hormonal and neuromuscular factors have been associated with this disparity. Research into whether genetic differences exist is limited. The purpose of this study was to compare gene expression in ruptured ACL tissue from young male and female athletes using microarray technology. Since X-and Y-chromosome-linked genetic differences are expected, this study only focused on identified genes that were not found on the X- or Y-chromosome. The authors hypothesize that there are significant differences in gene expression between young male and female ruptured ACL tissues, particularly as it relates to the extracellular matrix (ECM), a source of strength and resiliency in ligamentous tissue.
METHODS: This study was approved by the Institutional Review Board of the participating hospital system. A biopsy of normally discarded ruptured ACL tissue was obtained intraoperatively from seven male and seven female young athletic patients. Biopsies were divided into groups for histological and gene expression analyses. Histological specimens were stained with hematoxylin and eosin and trichrome. The specimens for gene expression analysis were frozen-ground and RNA was extracted and purified. Microarray analysis was performed using RNA isolated from four male and four female participants with non-contact injuries. Significant genes identified by microarray analysis were grouped into functionally associated networks using software analysis. Three genes of interest were chosen for further verification by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis from all 14 patients. Several statistical methods were used to examine data with p < 0.05 considered significant.
RESULTS: Microarray analysis identified 32 significantly differentially expressed genes in RNA isolated from young male and female ruptured ACL tissue, 14 of which were not X- or Y-chromosome linked. Analysis grouped these genes in skeletal muscular development and function and cellular growth, maintenance and proliferation pathways. In females compared to males, RT-qPCR confirmed statistically significant upregulation of gene expression in aggrecan and fibromodulin (FMOD) and downregulation in WNT1 inducible signaling pathway protein 2 (WISP2). On histological examination, no apparent morphological differences were identified between young male and female ruptured ACL tissue.
DISCUSSION AND CONCLUSION: Genes identified in this study as distinctly different produce major molecules in the ACL extracellular matrix. The significant upregulation of proteoglycans (aggrecan) and FMOD (extracellular matrix-regulating protein) and downregulation of WISP2 (involved in collagen turnover and production) may account for weaker ACLs in females than in males. This study is the first to demonstrate the utility of microarray analysis to compare female and male ruptured ACL tissue.

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