title: Does Anterior Cruciate Ligament Innervation Matter for Joint Function and Development of Osteoarthritis?
abstract: Complications following anterior cruciate ligament (ACL) injury and reconstruction that include chronic dysfunction, second ACL injury, and posttraumatic osteoarthritis (OA) may be interrelated and stem from the inability to fully restore native ACL integrity and function. The loss of ACL sensory input following injury may significantly contribute to joint dysfunction. We developed a novel preclinical animal model to assess the contributions of ACL sensory afferents to knee joint function and health. We hypothesized that ACL sensory denervation would manifest in knee joint dysfunction and development of early OA. Purpose-bred, adult research dogs (n= 9 dogs, 18 knees) underwent arthroscopic surgery to create three treatment groups: (1) partial ACL tear, (2) ACL denervated, and (3) whole-joint denervated. A neurotoxin injected directly into the ACL or into the joint space was used to induce sensory denervation, and sham procedures were done on contralateral knees. After intervention, dogs participated in a regimented exercise program. Gait analysis and clinically relevant functional assessments were performed. At week 12, the animals were humanely euthanatized for arthroscopic, gross, and histologic assessments. ACL partial tear group demonstrated the greatest overall knee dysfunction. Clinical measures of function revealed a significant difference between the ACL partial tear and ACL denervated group (p< 0.05), but these differences were not observed between the ACL and whole-joint denervated groups (p> 0.05). A significant reduction in limb loading was experienced by the ACL partial tear group compared with controls (p< 0.05) but not between other groups. Arthroscopic evaluation found no evidence for overt articular cartilage damage, meniscal pathology, or osteophyte formation was noted in any group. No significant differences (p> 0.05) were observed in ACL pathology and OA severity scores between the ACL partial tear and the ACL denervated groups. The results of our study indicate that ACL sensory loss may contribute to joint dysfunction and subsequent OA changes. Further investigation and development of this model are important to improve clinical therapies and optimize patient outcomes following ACL injury.
authors.affiliation: Orthopedic Biomechanics Laboratory, Orthopedic Surgery, and Sports Medicine Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Nagelli
authors.affiliation: Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri.
authors.forename: James L
authors.initials: JL
authors.lastname: Cook
authors.affiliation: Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri.
authors.forename: Kei
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Bozynski
authors.affiliation: Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri.
authors.forename: Richard
authors.initials: R
authors.lastname: Ma
authors.affiliation: Orthopedic Biomechanics Laboratory, Orthopedic Surgery, and Sports Medicine Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Hewett
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000294:innervation*; D000070598:Anterior Cruciate Ligament Injuries / Q000503:physiopathology*; D003714:Denervation; D004285:Dogs; D007719:Knee Joint / Q000503:physiopathology*; D023421:Models, Animal; D020370:Osteoarthritis, Knee / Q000503:physiopathology*