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

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. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1910-1919, 2019.