Metabolism and composition of the canine anterior cruciate ligament relate to differences in knee joint mechanics and predisposition to ligament rupture

Abstract

Purpose: The objective of this study was to determine whether differences in the composition and metabolism of the extracellular matrix (ECM) in canine anterior cruciate ligaments (ACLs) might relate to mechanical properties of the canine knee. Variations in ACL biochemistry and knee mechanics could account for divergent predispositions to ligament rupture.Methods: Eleven knee joints were obtained from both cadaveric Labrador Retrievers (rupture predisposed) and ex-racing Greyhounds (non-rupture predisposed). Anterioposterior laxity and tensile testing determined mechanical properties of the knee joints and ACL samples respectively. The thermal properties of the collagenous matrix were determined by differential scanning calorimetry (DSC) and the biochemical properties by measuring collagen content, collagen cross-links, glycosaminoglycan (GAG) levels, matrix nietalloproteinase-2 (MMP-2), tissue inhibitors of metalloproteinase (TIMP).Results: The anterioposterior laxity was significantly greater (p = 0.04) in the Labrador Retriever knee joints, and their ACLs tended to be weaker (p = 0.06). Greater collagen turnover was demonstrated by significantly higher (p = 0.02) concentrations of pro-MMP-2, and lower enthalpy of denaturation (p = 0.05) in Labrador Retriever ACLs.Conclusions: The different metabolism of the collagenous matrix in the ACLs of dogs predisposed to rupture was related to greater knee joint laxity and lower ligament material properties (ultimate tensile stress). This may be suggestive of a link between ligament rupture and eventual knee osteoarthritis in both dogs and humans.

Cruciate ligament laxity and femoral intercondylar notch narrowing in early‐stage knee osteoarthritis

“…Because critical strain or deformation is intimately related to the extent of collagen crimp and fibril organization (34,36,49), it follows that increased laxity of the DH guinea pig ACL postmaturation is attributable to increased crimp periodicity and poor fiber alignment, perhaps due to elevated tissue turnover. In a recent study by Comerford et al (50), elevated AP knee laxity in dogs was associated with elevated MMP-2 content in the ACL. These findings are consistent with our hypothesis that increased turnover of the ACL results in a laxer ligament and increased AP knee laxity.…”

ACL Research Retreat VII: An Update on Anterior Cruciate Ligament Injury Risk Factor Identification, Screening, and Prevention

“…[130][131][132][133][134][135] Greater magnitudes of knee laxity may have both biological and biomechanical consequences. Evidence from animal studies [148][149][150] suggests that greater knee laxity is associated with ligament biomarkers indicative of greater collagen turnover, more immature cross-links, and lower failure loads. Biomechanically, greater magnitudes of knee laxity and general joint laxity have been associated with higher-risk landing strategies more often observed in females (eg, greater knee-extensor loading and stiffening, greater dynamic knee valgus), particularly in the planes of motion where greater knee laxity is observed.…”

“…* For example, interactions among hormones, mechanical stress, and altered ACL structure and metabolism have been observed in some animal models. 148,205,206 In recent years, the hormone relaxin has gained attention as a potential ACL injury risk factor based on a prospective study of National Collegiate Athletic Association Division I female athletes that showed elevated concentrations in those with ACL injuries compared with uninjured controls. 207 Even though studies examining the effect of relaxin on collagen metabolism in human knee ligaments in situ are lacking, in vivo and in vitro animal studies and human cell culture studies suggest that relaxin administered at physiologic levels can have a profound effect on soft tissue remodeling.…”

ACL Research Retreat V: An Update on ACL Injury Risk and Prevention, March 25–27, 2010, Greensboro, NC

“…In animal models, interactions have been noted among mechanical stress, hormones, and altered ACL structure and metabolism. [95][96][97] What We Don't Know 1. What is the underlying mechanism for the increased likelihood of ACL injury in the preovulatory phase?…”