J Knee Surg 2018; 31(06): 520-527
DOI: 10.1055/s-0037-1604151
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biomechanics and Microstructural Analysis of the Mouse Knee and Ligaments

Camila B. Carballo
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
2   Programa de Pós-graduação em Anatomia Patológica, Universidade Federal do Rio de Janeiro (UFRJ), RJ, Brazil
,
Ian D. Hutchinson
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
,
Zoe M. Album
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
,
Michael J. Mosca
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
,
Arielle Hall
2   Programa de Pós-graduação em Anatomia Patológica, Universidade Federal do Rio de Janeiro (UFRJ), RJ, Brazil
,
Scott Rodeo Jr.
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
,
Liang Ying
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
,
Xiang-Hua Deng
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
,
Scott A. Rodeo
1   Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York
› Author Affiliations
Further Information

Publication History

01 March 2017

31 May 2017

Publication Date:
18 July 2017 (online)

Abstract

The purpose of this study is to determine the feasibility of using murine models for translational study of knee ligament injury, repair, and reconstruction. To achieve this aim, we provide objective, quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of knee ligaments of 44 male mice (C57BL6, 12 weeks of age). Biomechanical testing determined the load-to-failure force, stiffness, and the site of ligament failure for the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and the medial and lateral collateral ligaments (MCL and LCL). These data are complemented by histological characterization of each of the knee ligaments. In addition, the osseous morphology of the mouse knee was examined using high-resolution nanofocus computed tomography (CT), while standard micro-CT was employed to measure bone morphometrics of the distal femur and proximal tibia. Collectively, our findings suggest that the gross anatomy of the mouse knee is similar to the human knee despite some minor differences and features unique to the murine knee. The ACL had the highest load to failure (5.60 ± 0.75 N), the MCL (3.33 ± 1.45 N), and the PCL (3.45 ± 0.84 N) were similar, and the LCL (1.44 ± 0.37 N) had the lowest load to failure and stiffness. Murine models provide a unique opportunity to focus on biological processes that impact ligament pathology and healing due to the availability of transgenic strains. Our data support their use as a translational platform for the in vivo study of ligament injury, repair, and reconstruction.

 
  • References

  • 1 Sanders TL, Maradit Kremers H, Bryan AJ. , et al. Incidence of anterior cruciate ligament tears and reconstruction: a 21-year population-based study. Am J Sports Med 2016; 44 (06) 1502-1507
  • 2 Brophy RH, Kovacevic D, Imhauser CW. , et al. Effect of short-duration low-magnitude cyclic loading versus immobilization on tendon-bone healing after ACL reconstruction in a rat model. J Bone Joint Surg Am 2011; 93 (04) 381-393
  • 3 Gulotta LV, Rodeo SA. Biology of autograft and allograft healing in anterior cruciate ligament reconstruction. Clin Sports Med 2007; 26 (04) 509-524
  • 4 Benjamin M, Toumi H, Ralphs JR, Bydder G, Best TM, Milz S. Where tendons and ligaments meet bone: attachment sites (‘entheses’) in relation to exercise and/or mechanical load. J Anat 2006; 208 (04) 471-490
  • 5 Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR. The skeletal attachment of tendons--tendon “entheses”. Comp Biochem Physiol A Mol Integr Physiol 2002; 133 (04) 931-945
  • 6 Galatz LM, Gerstenfeld L, Heber-Katz E, Rodeo SA. Tendon regeneration and scar formation: the concept of scarless healing. J Orthop Res 2015; 33 (06) 823-831
  • 7 Carpenter JE, Hankenson KD. Animal models of tendon and ligament injuries for tissue engineering applications. Biomaterials 2004; 25 (09) 1715-1722
  • 8 Moran CJ, Barry FP, Maher SA, Shannon FJ, Rodeo SA. Advancing regenerative surgery in orthopaedic sports medicine: the critical role of the surgeon. Am J Sports Med 2012; 40 (04) 934-944
  • 9 St Pierre P, Olson EJ, Elliott JJ, O'Hair KC, McKinney LA, Ryan J. Tendon-healing to cortical bone compared with healing to a cancellous trough. A biomechanical and histological evaluation in goats. J Bone Joint Surg Am 1995; 77 (12) 1858-1866
  • 10 Rodeo SA, Arnoczky SP, Torzilli PA, Hidaka C, Warren RF. Tendon-healing in a bone tunnel. A biomechanical and histological study in the dog. J Bone Joint Surg Am 1993; 75 (12) 1795-1803
  • 11 Grana WA, Egle DM, Mahnken R, Goodhart CW. An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med 1994; 22 (03) 344-351
  • 12 Carbone A, Carballo C, Ma R. , et al. Indian hedgehog signaling and the role of graft tension in tendon-to-bone healing: evaluation in a rat ACL reconstruction model. J Orthop Res 2016; 34 (04) 641-649
  • 13 Hast MW, Zuskov A, Soslowsky LJ. The role of animal models in tendon research. Bone Joint Res 2014; 3 (06) 193-202
  • 14 Schweitzer R, Chyung JH, Murtaugh LC. , et al. Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments. Development 2001; 128 (19) 3855-3866
  • 15 Ito Y, Toriuchi N, Yoshitaka T. , et al. The Mohawk homeobox gene is a critical regulator of tendon differentiation. Proc Natl Acad Sci U S A 2010; 107 (23) 10538-10542
  • 16 Scott A, Sampaio A, Abraham T, Duronio C, Underhill TM. Scleraxis expression is coordinately regulated in a murine model of patellar tendon injury. J Orthop Res 2011; 29 (02) 289-296
  • 17 Brown JP, Finley VG, Kuo CK. Embryonic mechanical and soluble cues regulate tendon progenitor cell gene expression as a function of developmental stage and anatomical origin. J Biomech 2014; 47 (01) 214-222
  • 18 Glasson SS, Blanchet TJ, Morris EA. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis and cartilage/OARS. Osteoarthritis Research Society 2007; 15: 1061-1069
  • 19 Gilday SD, Casstevens EC, Kenter K, Shearn JT, Butler DL. Murine patellar tendon biomechanical properties and regional strain patterns during natural tendon-to-bone healing after acute injury. J Biomech 2014; 47 (09) 2035-2042
  • 20 Boivin GP, Elenes EY, Schultze AK, Chodavarapu H, Hunter SA, Elased KM. Biomechanical properties and histology of db/db diabetic mouse Achilles tendon. Muscles Ligaments Tendons J 2014; 4 (03) 280-284
  • 21 Bell R, Taub P, Cagle P, Flatow EL, Andarawis-Puri N. Development of a mouse model of supraspinatus tendon insertion site healing. J Orthop Res 2015; 33 (01) 25-32
  • 22 Liu X, Laron D, Natsuhara K, Manzano G, Kim HT, Feeley BT. A mouse model of massive rotator cuff tears. J Bone Joint Surg Am 2012; 94 (07) e41
  • 23 Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 2010; 25 (07) 1468-1486
  • 24 Verdelis K, Lukashova L, Atti E. , et al. MicroCT morphometry analysis of mouse cancellous bone: intra- and inter-system reproducibility. Bone 2011; 49 (03) 580-587
  • 25 Woo SL, Hollis JM, Adams DJ, Lyon RM, Takai S. Tensile properties of the human femur-anterior cruciate ligament-tibia complex. The effects of specimen age and orientation. Am J Sports Med 1991; 19 (03) 217-225
  • 26 Fu FH, Bennett CH, Lattermann C, Ma CB. Current trends in anterior cruciate ligament reconstruction. Part 1: biology and biomechanics of reconstruction. Am J Sports Med 1999; 27 (06) 821-830
  • 27 Halewood C, Amis AA. Clinically relevant biomechanics of the knee capsule and ligaments. Knee Surg Sports Traumatol Arthrosc 2015; 23 (10) 2789-2796
  • 28 Wilson WT, Deakin AH, Payne AP, Picard F, Wearing SC. Comparative analysis of the structural properties of the collateral ligaments of the human knee. J Orthop Sports Phys Ther 2012; 42 (04) 345-351
  • 29 Woo SL, Orlando CA, Gomez MA, Frank CB, Akeson WH. Tensile properties of the medial collateral ligament as a function of age. J Orthop Res 1986; 4 (02) 133-141
  • 30 Chang JC, Sebastian A, Murugesh DK. , et al. Global molecular changes in a tibial compression induced ACL rupture model of post-traumatic osteoarthritis. J Orthop Res 2017; 35 (03) 474-485
  • 31 Christiansen BA, Anderson MJ, Lee CA. , et al. Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis. Osteoarthritis and cartilage/OARS. Osteoarthritis Research Society 2012; 20: 773-782
  • 32 Shelburne KB, Pandy MG, Anderson FC, Torry MR. Pattern of anterior cruciate ligament force in normal walking. J Biomech 2004; 37 (06) 797-805
  • 33 Proffen BL, McElfresh M, Fleming BC, Murray MM. A comparative anatomical study of the human knee and six animal species. Knee 2012; 19 (04) 493-499
  • 34 Hildebrand C, Oqvist G, Brax L, Tuisku F. Anatomy of the rat knee joint and fibre composition of a major articular nerve. Anat Rec 1991; 229 (04) 545-555
  • 35 Whiston TB, Walmsley R. Some observations on the reactions of bone and tendon after tunnelling of bone and insertion of tendon. J Bone Joint Surg Br 1960; 42-B: 377-386
  • 36 Woo SL, . J, Butler D, Lyon R, Torzilli P, Akeson W, Cooper R, Oakes B. Ligament, tendon, and joint capsule insertions to bone. In: Woo SLY, Buckwalter JA. , ed. Injury and Repair of the Musculoskeletal Soft Tissues. Park Ridge, Illinois: The American Academy of Orthopaedic Surgeons; 1988: 129-166
  • 37 Duncan W, Dahm DL. Clinical anatomy of the fabella. Clin Anat 2003; 16 (05) 448-449