Morphology of Mouse Anterior Cruciate Ligament‐Complex Changes Following Exercise During Pubertal Growth

Abstract

Postnatal development and the physiological loading response of the anterior cruciate ligament (ACL) complex (ACL proper, entheses, and bony morphology) is not well understood. We tested whether the ACL-complex of two inbred mouse strains that collectively encompass the musculoskeletal variation observed in humans would demonstrate significant morphological differences following voluntary cage-wheel running during puberty compared with normal cage activity controls. Female A/J and C57BL/6J (B6) 6-week-old mice were provided unrestricted access to a standard cage-wheel for 4 weeks. A/J-exercise mice showed a 6.3% narrower ACL (p = 0.64), and a 20.1% more stenotic femoral notch (p < 0.01) while B6-exercise mice showed a 12.3% wider ACL (p = 0.10), compared with their respective controls. Additionally, A/J-exercise mice showed a 5.3% less steep posterior medial tibial slope (p = 0.07) and an 8.8% less steep posterior lateral tibial slope (p = 0.07), while B6-exercise mice showed a 9.8% more steep posterior medial tibial slope (p < 0.01) than their respective controls. A/J-exercise mice also showed more reinforcement of the ACL tibial enthesis with a 20.4% larger area (p < 0.01) of calcified fibrocartilage distributed at a 29.2% greater depth (p = 0.02) within the tibial enthesis, compared with their controls. These outcomes suggest exercise during puberty significantly influences ACL-complex morphology and that inherent morphological differences between these mice, as observed in their less active genetically similar control groups, resulted in a divergent phenotypic outcome between mouse strains.

Tibiofemoral bony morphology features associated with ACL injury and sex utilizing three‐dimensional statistical shape modeling

“…Furthermore, most bony morphological features are considered to be innate shapes that do not change. However, data exist showing that repeated loading from training and sport or after ACL reconstruction can cause bone remodeling 39–42 . In the future, bony morphological differences will be analyzed between athletes in different types of sports.…”

The Anterior Cruciate Ligament Can Become Hypertrophied in Response to Mechanical Loading: A Magnetic Resonance Imaging Study in Elite Athletes

“…In addition to the group of weight lifters with hypertrophied ACLs potentially due to their training through puberty, 17 exercise through periods of growth has also been shown to increase the ACL size and improve its mechanical properties in animal models. 6,36,42 Therefore, the potential for the ACL to be ''trained,'' so to speak, to become larger, more robust, and thus less at risk of injuries is apparent, but many critical questions remain unanswered.…”

“…Significant increases in ACL strength (ie, greater energy at ligament failure) and stiffness have been reported in growing rats and rabbits. 6,42 Also, most recently, Schlecht et al 36 revealed that exercise during puberty significantly increased the ACL CSA in a mouse model. Evidence of hypertrophied ACLs also exists for the human ACL.…”

“…9,18,25,43 Although morphological risk factors as a group have been largely characterized as nonmodifiable, 31,33 ACL surface area and cross-sectional area (CSA) have potential for modifiability, especially during periods of growth and development. 17,36 Perhaps the ACL could be ''trained'' to become larger, more robust, and thus less prone to injuries.…”

“…We hypothesized that these athletes would have significantly greater ACL CSAs in the leg that is loaded the most in comparison with the contralateral control leg. 6,17,36,42 Additionally, we sought to determine whether bilateral differences in the ACL CSA were related to the age of training onset as well as the number of years of training. We predicted a significant negative correlation between the bilateral difference in the ACL CSA and age of training onset.…”