Sex, Collagen Expression, and Anterior Cruciate Ligament Strength in Rats (original) (raw)
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Matrix Biology, 2004
Female athletes are two to eight times more likely to suffer a knee or ankle ligament injury than male athletes, and sex hormones have been considered to play an important role in the injury. Because ligaments are always under mechanical loading during sports, mechanical force is also a critical factor in ligament injuries. In this study, the effects of estrogen and mechanical loading on the gene expression of three major components of ligament-collagen type I, type III, and biglycan-in primary cultured porcine anterior cruciate ligament (ACL) fibroblasts were investigated individually and collectively using reverse transcript-polymerase chain reaction (RT-PCR). The results revealed that cyclic tensile loading alone increased the messenger RNA expression of collagen I but did not affect that of collagen III and biglycan, and estrogen alone increased the gene expression of collagen I and III but not of biglycan. However, combined administration of estrogen and cyclic loading inhibited the mRNA expression of all the three genes. These results suggested that the inhibition of the gene expression of major extracellular matrix component molecules caused by the combined effects of estrogen and mechanical loading, unique to females, might be responsible for the increased incidence of ligaments injury in female athletes. D
Knee ligament mechanical properties are not influenced by estrogen or its receptors
AJP: Endocrinology and Metabolism, 2006
Women are at greater risk of tearing their knee anterior cruciate ligament (ACL) than men participating in similar athletic activities. There is currently no conclusive explanation for this disparity; however, as ACL injuries in women have been linked with estrogen fluctuations during the menstrual cycle, one hypothesis is that estrogen has a direct detrimental effect on knee ligament mechanical properties. This study investigated the influence of estrogen and its receptors (ER␣ and ER) on knee ligament mechanical properties. This was achieved by testing the viscoelastic and tensile mechanical properties of knee medial collateral ligaments (MCL) and ACLs from: 1) male Sprague-Dawley rats treated with either estrogen (17␣-ethynylestradiol; 0.03 mg/kg) or an ER␣-specific agonist (propyl pyrazole triol; 2 mg/kg), and 2) female mice with a null mutation of the gene encoding for ER. Estrogen treatment had no significant effects on the viscoelastic or tensile mechanical properties of the rat MCL or ACL. Similarly, pharmacological stimulation of ER␣ using a selective agonist in rats and genetic modulation of ER by null mutation of its gene in mice did not influence MCL or ACL properties. These data indicate that estrogen does not have a major direct effect on ligament mechanical properties. Energies for the prevention of the disproportionately high rate of knee ligament injuries in women may be better spent focusing on more established and modifiable risk factors, such as abnormalities in neuromuscular control about the knee.
The influence of sex hormones on anterior cruciate ligament ruptures in males
Knee Surgery, Sports Traumatology, Arthroscopy, 2014
Purpose The purpose of this study was to determine the difference in the concentrations of testosterone, 17-b estradiol and progesterone between female patients with and without ACL rupture and the possible effect of these hormones on generalised joint laxity. Methods Female subjects with non-contact knee joint injury were included in this study. They were divided into two groups: the examined group, consisting of female subjects with ACL rupture, and the control group, consisting of female patients without ACL rupture. In the next step, the patients from these two groups were paired off on the basis of three factors: the level of professional sports involvement (including the type of sports activity), the side of the body where the injury had occurred (left or right) and the age of the subjects. In the end, there were 12 pairs (24 subjects). The concentrations of sex hormones were established from saliva specimens with the aid of the Salimetrics enzyme immunoassay. Generalised joint laxity was tested with the aid of the ''laxity score'' according to Beighton, Solomon and Soskolne. Results Female subjects with ACL rupture had significantly lower concentrations of testosterone (p \ 0.01), significantly lower concentrations of 17-b estradiol (p \ 0.05) and significantly lower concentrations of progesterone (p \ 0.01) than female subjects with intact ACL. Conclusions Decreased concentrations of testosterone, 17-b estradiol or progesterone may be a risk factor leading to ACL rupture. The concentrations of these hormones do not affect generalised joint laxity. Additional research on a larger group of patients is necessary to further determine the effects of these hormones on generalised joint laxity and ACL ruptures. Young female athletes with lower concentrations of sex hormones are more prone to anterior
Proteomic Differences between Male and Female Anterior Cruciate Ligament and Patellar Tendon
PLoS ONE, 2014
The risk of anterior cruciate ligament (ACL) injury and re-injury is greater for women than men. Among other factors, compositional differences may play a role in this differential risk. Patellar tendon (PT) autografts are commonly used during reconstruction. The aim of the study was to compare protein expression in male and female ACL and PT. We hypothesized that there would be differences in key structural components between PT and ACL, and that components of the proteome critical for response to mechanical loading and response to injury would demonstrate significant differences between male and female. Two-dimensional liquid chromatography-tandem mass spectrometry and a label-free quantitative approach was used to identify proteomic differences between male and female PT and ACL. ACL contained less type I and more type III collagen than PT. There were tissue-specific differences in expression of proteoglycans, and ACL was enriched in elastin, tenascin C and X, cartilage oligomeric matrix protein, thrombospondin 4 and periostin. Between male and female donors, alcohol dehydrogenase 1B and complement component 9 were enriched in female compared to male. Myocilin was the major protein enriched in males compared to females. Important compositional differences between PT and ACL were identified, and we identified differences in pathways related to extracellular matrix regulation, complement, apoptosis, metabolism of advanced glycation end-products and response to mechanical loading between males and females. Identification of proteomic differences between male and female PT and ACL has identified novel pathways which may lead to improved understanding of differential ACL injury and re-injury risk between males and females.
Journal of Orthopaedic Research, 2008
The purpose of this study was to investigate the existence of sex-based differences in the ultrastructural characteristics of the human anterior cruciate ligament (ACL) as the underlying cause of differences in the structural and mechanical properties between sexes. The ACL of six male and six female cadaveric donors were randomly chosen from a pool of 10 male and 10 female ACLs that had previously been tested for their structural and mechanical properties. Eighteen tissue samples from the distal, proximal, and middle sections of the anteromedial and posterolateral bundles were analyzed by transmission electron microscopy. Female ACLs exhibited both lower fibril concentration and lower percent area occupied by collagen fibrils ( p < 0.05) compared to males. There was also a difference in the fibril diameters ( p < 0.05); donor age, height, body mass, and body mass index contributed significantly to this difference. In females, ACL stiffness and modulus of elasticity were highly correlated to fibril concentration (r ¼ 0.96 and 0.97, respectively); in males ACL failure load and strength were highly correlated to percent area occupied by collagen (r ¼ 0.96 and 0.96, respectively). These differences in ultrastructure may underlie differences in ACL properties between sexes. ß
Anterior Cruciate Ligament Biology and Its Relationship to Injury Forces
Orthopedic Clinics of North America, 2006
The anterior cruciate ligament (ACL) is one of primary stabilizers of the knee, and disruption of this ligament is three to ten times more common in female athletes than male athletes who participate in the same sports at the same level of competition . These knee injuries are a growing cause for concern because of the association with earlyonset, posttraumatic osteoarthritis after severe ligament tears. Despite an abundance of theories about why female athletes are more susceptible to this injury and proposed neuromuscular training programs designed to protect the knee, no definitive causal link has been found among mechanisms of injury, sex, and ACL rupture.
Sex Comparisons of In Vivo Anterior Cruciate Ligament Morphometry
Journal of Athletic Training, 2019
Context: Females have consistently higher anterior cruciate ligament (ACL) injury rates than males. The reasons for this disparity are not fully understood. Whereas ACL morphometric characteristics are associated with injury risk and females have a smaller absolute ACL size, comprehensive sex comparisons that adequately account for sex differences in body mass index (BMI) have been limited. Objective: To investigate sex differences among in vivo ACL morphometric measures before and after controlling for femoral notch width and BMI. Design: Cross-sectional study. Setting: Laboratory. Patients or Other Participants: Twenty recreationally active men (age ¼ 23.2 6 2.9 years, height ¼ 180.4 6 6.7 cm, mass ¼ 84.0 6 10.9 kg) and 20 recreationally active women (age ¼ 21.3 6 2.3 years, height ¼ 166.9 6 7.7 cm, mass ¼ 61.9 6 7.2 kg) participated. Main Outcome Measure(s): Structural magnetic resonance imaging sequences were performed on the left knee. Anterior cruciate ligament volume, width, and cross-sectional area measures were obtained from T2-weighted images and normalized to femoral notch width and BMI. Femoral notch width was measured from T1-weighted images. We used independentsamples t tests to examine sex differences in absolute and normalized measures.
The adaptability of tendon to loading differs in men and women
International Journal of Experimental Pathology, 2007
It is well established that women are more likely to sustain certain connective tissue injuries than men during physical activities (Jones et al. 1993; Bijur et al. 1997). For example, the incidence of anterior cruciate ligament injuries in women is reported to be up to six times that in men participating in similar physical activities (Bjordal et al. 1997; Hewett et al. 2001). The annual cost for these injuries is large (Griffin et al. 2000), and yet the underlying reasons for this genderspecific difference in connective tissue injury remains an enigma. Oestrogen receptor activity is modulated by estradi-ol (Ciana et al. 2003), and in vitro studies show that estradiol has an inhibiting effect upon collagen formation in ligaments(Liu et al. 1997; Yu et al. 2001), which gives us reason to believe that tendon tissue adaptation to mechanical loading may differ between men and women. We investigated whether a gender difference existed with regards to resting and exercise-induced collagen protein synthesis, tissue mechanical properties and morphology of human tendon, and to what extent this is influenced by circulating levels of estradiol.
2014
ABSTRACT Introduction Ligament reconstruction of the anterior cruciate ligament (ACL) is one of the most frequent arthroscopic procedures. According to the Technical Agency for Information on Hospitalizations (ATIH) 41,122 ligament reconstructions were performed in France in 2012. Treatment of the injury is costly and not always successful at returning patients to their preinjury activity level. Identification of all factors associated with increased risk of ACL injury during sport is important to provide an appropriate level of counseling and programs for prevention. These factors have been categorized as intrinsic (inherent to the individual athlete) or extrinsic (external to the athlete). Risk of ACL injury in female athletes depending on sports Female athletes have been identified at increased risk of injuring their ACL during certain sports, with reported injury rates that are 3.6 times greater for basketball and 5.1 times greater for handball when compared with male athletes who participate in these sports at similar levels of play. Extrinsic risk factors Several extrinsic factors seem increase the risk of ACL injury in both female and male athletes with a slightly increased risk in female: competition, wet and rainy weather, the type and number of cleats, the design of the shoe, the type of grass, artificial grass or floor surface and previous ACL reconstruction. Intrinsic risk factors Several anatomic risk factors have been identified, mainly an increased anterior-posterior knee laxity, a smaller intercondylar notch width with a shorter ACL, and a greater condyle offset ratio. Neuromuscular and biomechanical risk factors are also involved as increased dynamic valgus and muscle and proprioceptive deficit of the non-dominant leg in female. The hormonal theory is based on several reports of elevated ACL tear rates in pre- as compared to postovulatory phase. Other risk factors were evocated: a familial predisposition to noncontact ACL tears, genetic factors and a higher body mass index. Multivariate risk factor analysis Given the multiplicity of risk factors it seems important to develop multivariable models but very few studies have followed this approach. Conclusion Several intrinsic factors may explain the sex-ration in ACL tear but intrinsic and extrinsic risk factors act in combination to increase the risk of ACL injury. The identification of these factors has led to the development of appropriate prevention programs with good but still insufficient results. Optimizing prevention requires the organization of large cohort studies for each sport, involving all participants. A generalization of multivariate statistical analyzes would take into account the possible interactions and to quantify the risk for each factor. Comprehensive prevention programs specific to each sport, incorporating all the factors, could then be developed.