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. Author manuscript; available in PMC: 2016 Nov 17.
Published in final edited form as: J Orthop Res. 2013 Jul 10;31(10):1555–1560. doi: 10.1002/jor.22393

Replication of Chronic Abnormal Cartilage Loading by Medial Meniscus Destabilization for Modeling Osteoarthritis in the Rabbit Knee In Vivo

Marut Arunakul 1,2, Yuki Tochigi 1, Jessica E Goetz 1,3, Bryce W Diestelmeier 1,3, Anneliese D Heiner 1,3, M James Rudert 1, Douglas C Fredericks 1, Thomas D Brown 1,3, Todd O McKinley 1
PMCID: PMC5113956  NIHMSID: NIHMS697474  PMID: 23843150

Abstract

Medial meniscus destabilization (MMD) is a surgical insult technique for modeling osteoarthritis (OA) by replicating chronic abnormal cartilage loading in animal joints in vivo. The present study aimed to characterize the immediate biomechanical effects (ex vivo) and short-term histological consequences (in vivo) of MMD in the rabbit knee. In a compressive loading test, contact stress distribution in the medial compartment was measured in eight cadaver rabbit knees, initially with all major joint structures uninjured (Baseline), after MMD, and finally after total medial meniscectomy (TMM). Similarly, the effects on sagittal joint stability were determined in an anterior-posterior drawer test. These biomechanical (ex vivo) data indicated that both MMD and TMM caused significant (p < 0.001), distinct (> 1.5-fold) elevation of peak local contact stress in the medial compartment, while leaving whole-joint stability nearly unchanged. Histological consequences in vivo were assessed in a short-term (8-week) survival series of MMD or TMM (5 animals for each group), and both caused moderate cartilage degeneration in the medial compartment. The MMD insult, which is feasible through posterior arthrotomy alone, is as effective as TMM for modeling injurious-level chronic abnormal cartilage loading in the rabbit knee medial compartment in vivo, while minimizing potential confounding effects from whole-joint instability.

Keywords: post-traumatic osteoarthritis, survival animal model, rabbit knee, meniscus, contact stress

INTRODUCTION

Osteoarthritis (OA) is a very common joint disease that causes pain and disability in many people. A substantial fraction (almost 12%) of the overall burden of OA arises secondary to joint trauma,1 namely post-traumatic OA. Many factors affect the development and progression of post-traumatic OA, including anatomic location, injury severity, immunological responses, residual biomechanical abnormalities after primary treatment, and joint usage.1-5 Of these, acute articular surface damage6 and chronic abnormal joint contact mechanics4 are well-recognized determinants of clinical outcome. A survival animal model in which these two major pathogenetic factors cause predictable OA development is crucial to study the disease mechanisms of this type of OA, and to develop treatments for it.

The rabbit knee has been commonly utilized for survival animal models in OA research,7 due to its relatively large physical size being well-suited for surgical insult, and due to the knees’ relatively thick cartilage (particularly in the medial compartment), which facilitates histological and/or biochemical evaluation. A previous study8 found that surgical resection of the entire medial meniscus (i.e., total meniscectomy) in the rabbit knee caused cartilage degeneration that developed over a relatively long time period (13 to 40 weeks). This modest mid- to long-term effect is well suited for testing the effects of therapeutic intervention. Completing a total meniscectomy while preserving articular cartilage typically requires two (anteromedial and posteromedial) arthrotomies. This approach is somewhat unfavorable for minimizing animals’ distress. Particularly, surgical insult to the extensor mechanism (necessarily involved in the anteromedial para-patellar arthrotomy) may affect whole-joint function, in turn potentially affecting the cartilage condition even after sham (control) surgery. A less invasive, but similarly effective surgical insult is therefore desirable.

A well-suited insult modality for this purpose is surgical destabilization of the medial meniscus, achieved through posterior arthrotomy.9 The posterior (popliteal) approach utilized in this technique can be shared with articular surface insults (i.e., osteochondral defect10 or blunt impaction11,12) in the primary weight-bearing region on the medial femoral condyle. (Note: since the rabbit's physiological knee flexion angle is 90 – 160 degrees,13,14 the most habitually loaded regions on the femoral condyles are located on the posterior aspect, rather than inferiorly.) In this technique, the posterior root of the medial meniscus is sharply released from the tibia, while preserving all major joint structures. Particularly, since the extensor mechanism is left completely uninjured, the effects on whole-joint stability also should be minimal, thus helping preserve physiologic usage of the experimental joint. The primary objective of the present study was to determine the immediate effects of the medial meniscus destabilization (MMD) insult on rabbit knee joint mechanics. The hypothesis tested was that medial meniscus destabilization would significantly elevate contact stresses in the rabbit knee medial compartment, similarly to total meniscectomy (TMM), but while leaving whole-joint stability unchanged. In addition, the effects of these two types of surgical insult on cartilage health in vivo were tested in a survival animal series. The secondary hypothesis was that medial meniscus destabilization would predictably cause modest cartilage degeneration in the rabbit knee medial compartment, again similarly to total meniscectomy.

METHODS

Cadaver Experimentation

A total of sixteen New Zealand White rabbit cadaver knees (each from a different animal) were utilized. These specimens were dissected free from soft tissue, with all major knee ligaments left uninjured. Eight specimens were utilized for an axial compression test to measure contact stress distribution in the medial compartment, and the remaining eight were utilized for a sagittal-plane laxity test.

In the axial compression test, each rabbit knee was tested as a whole-joint preparation, with its distal femur and proximal tibia potted into separate polymethyl methacrylate blocks. The specimen was mounted in a custom-designed loading device actuated by an electromechanical materials testing machine (MTS Insight® 1, MTS Systems Corp., Eden Prairie, Minnesota, USA) (Figure 1A), with the knee positioned at a physiological flexion angle (i.e., approximately 135 degrees flexion13,14). Adduction/abduction about the axis aligned with the center of the knee was left unrestricted, allowing the joint to align naturally while the load was being applied. Axial compression was linearly increased over two seconds to a physiologic-level force (80 N),15 held constant for two seconds, and then linearly decreased back to zero.

Figure 1.

Figure 1

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A: Loading fixture for the axial compression test. B: Schematic of film position registration using fiducial markers; C: Determination of contact patch location in a strip of film (X = centroid of contact patch, C = coronal position, and S = sagittal position).

Contact stress in the medial compartment was measured using pressure-sensitive film (Low Range Prescale®, Fujifilm Co., Tokyo, Japan). A film strip (10 × 30 mm) was inserted into the tibio-femoral joint space above the meniscus (Figure 1B). To measure changes in the contact location, the position of the film with respect to the femur was registered by pressing the film against two fiducial markers (K-wires), which were embedded anteriorly or posteriorly to the medial femoral condyle (Figures 1B&C). Films were digitized at a resolution of 0.085 mm/pixel, and were analyzed using a purpose-written program implemented in MATLAB® (MathWorks®, Natick, Massachusetts, USA). These analyses used a calibration curve that was generated using a 6.35 mm diameter rubber platen and ten known stress levels, to convert the pixel intensity values to contact stress values. This analysis program identified the outline(s) of the contact patch (based on an intensity threshold), and then calculated the total contact area, the peak local contact stress, and the contact location (coronal and sagittal position of the center of contact patch, Figure 1C).

Each specimen (Figure 2) was sequentially tested in three conditions; 1) initially with the menisci left intact (Baseline), 2) after medial meniscus destabilization (MMD), and 3) finially after total medial meniscectomy (TMM). For MMD, the posterior horn of the medial meniscus was surgically released from its tibial attachment, by sharply transecting the posterior root using a #11 scalpel. For TMM, the meniscal body was atraumatically released from the medial collateral ligament, using a blunt instrument (a curved mosquito hemostat). Then, the anterior horn was sharply released from its tibial attachment, and the whole meniscus was excised as a single piece. Finally, contact stress distributions in the medial compartment and lateral compartment (after total lateral meniscectomy) were simultaneously measured, so as to ensure the adequacy of load recovery by means of spatially integrating the measured contact stress (range: 84 to 119% of the applied load). Throughout these procedures, special care was taken to avoid iatrogenic damage to the stabilizing structures or to the articular cartilage. The sagittal-plane laxity test utilized a custom loading fixture (Figure 3) described elsewhere.16 Each specimen was fixed with the femur secured vertically by means of half-pins. The tibia was secured with transverse pins attached to a horizontal leg holder, with the knee held flexed at 90 degrees. The leg holder was in turn attached to a stepper motor-driven actuator. The actuator applied cyclic anterior and posterior knee drawer displacement at a test speed of 1 mm/sec, with limits for direction reversal set as ±20 N or ±3 mm, whichever was reached first. Force vs. displacement data were continuously recorded during loading. The test sequence consisted of four discrete cycles for adjustment of the “zero” displacement position, followed by four continuous cycles of preconditioning, and then four continuous loading cycles for data collection. The knee drawer force vs. displacement relationship was typically characterized by a sigmoid curve. AP stability of the knee was quantified in terms of the length of the low-resistance central flat portion of the curve within the range of ±5 N of drawer force, designated as the neutral-zone length (Figure 3B). Each specimen was tested in the above-noted three conditions (Baseline, MMD, and TMM).

Figure 2.

Figure 2

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Left: Superior view of the rabbit knee tibial plateau with an intact medial meniscus (in a joint disarticulated for visualization). Right: Representative digitized Fujifilm images that indicate contact stress distribution in the medial compartment, for the three testing conditions in a joint. Approximate size of area covered by each contact patch image is illustrated as the dotted square on the tibial plateau photo. The corresponding numerical values for contact stress and contact area are indicated.

Figure 3.

Figure 3

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A: Custom loading fixture for the sagittal-plane laxity test. B: Definition of the neutral-zone length (NZL: displacement between ± 5 N) from the load-displacement relationship.

Survival Animal Series

Ten mature New Zealand white rabbits (12 to 15 months old, average weight 4.5 kg) were utilized with institutional approval. These animals received an insult surgery, either MMD or TMM (n = 5 per group), on their left knee, using standard inhalation anesthesia and aseptic technique. The surgical insult techniques were identical to those for cadaver experimentation. For the posterior surgery (for both MMD and TMM), the animal was placed in the prone position, and a medial popliteal longitudinal skin incision was made. Then, the posteromedial joint capsule was exposed through the intermuscular plane between the semimembranosus and medial gastrocnemius. The gastrocnemius tendon was retracted laterally, with the femoral insertion left intact. For the anterior surgery (only for TMM), after finishing the posterior surgery, the animal was inverted to the supine position, and an anterior arthrotomy was made through a medial parapatellar incision. The posterior incision was closed only by skin suture, while the anterior incision was closed by suturing the joint capsule and skin in layers, both using bioabsorbable suture. Postoperatively, the rabbits were allowed free cage activity and an ad lib diet.

All rabbits were sacrificed 8 weeks after index surgery. The experimental knees were prepared for cartilage histological evaluation following OARSI guidelines.17 From each joint, four sagittal sections (stained with Safranin-O/Fast Green) were prepared, one each from the medial and lateral femoral condyles and one each from the medial and lateral tibial plateaus. To establish baseline (control) information for the survival series, similarly prepared histological slides 8 weeks after sham surgery (including both anterior and posterior arthrotomies) were randomly selected from previous archival slides18 (20 slides: 4 surfaces for 5 animals). Histological sections were digitized at a resolution of 322.25 nm/pixel using a stage scanner microscope (Olympus® VS110™, Olympus America Inc., Center Valley, Pennsylvania, USA). From these high-resolution digital images, the regions of interest (the central 4 mm anterior-posterior span of the primary weight-bearing region in each section) were cropped, and exported at a resolution of 1.61 μm/pixel for histological evaluation. The femoral weight-bearing regions were defined as the site where cartilage was normally thickest on the posterior femoral condyle (either medial or lateral), while the tibial weight-bearing regions were the site normally uncovered by the meniscus.

Histological changes in these microscopic images were evaluated using an automated, objective, image analysis-based implementation of Mankin scoring.19 Four purpose-written computational routines were coded in MATLAB® (MathWorks®, Natick, Massachusetts, USA) to generate Mankin scores based on summation of the four component subscores (structure, proteoglycan content, cellularity, and tidemark integrity). These sub-scores were defined in accordance with deviations from normal cell density, proteoglycan staining intensity, and cartilage zonal thickness that were specific to each joint compartment and specific to the rabbit. Mankin scores were computed for each 0.5 mm segment of cartilage spanning the weight-bearing region. After omitting the highest and lowest scores (two segments), the remaining scores were averaged over the entire weight-bearing area to provide a whole-joint Mankin score. (As a result, this final “score” provided a quasi-continuous measure that considered both the severity and extent of cartilage degeneration across the surface of interest, consistent with the OARSI grading scale.17) The femoral and tibial surfaces in both the medial and lateral compartments were scored separately.

Statistical Analysis

For descriptive statistics, mean values and standard deviations were reported along with the highest and lowest values. Statistical comparisons across conditions/groups were performed using one-way repeated-measures ANOVA with Tukey-Kramer adjustment, with a significance level of alpha set at 0.05.

RESULTS

Cadaver Experimentation (Ex Vivo)

Contact stress distribution changes observed in the axial compression test (Figures 1 and 2) indicated that both MMD and TMM significantly decreased contact area in the medial compartment (p < 0.001, for both) relative to Baseline (Figure 4A). The relative contact area change was –41.1 ± 5.4% (range: –49 to –35%) for MMD and –40 ± 5.9% (–50 to –32%) for TMM. The mean absolute difference between MMD and TMM was only 1.7 ± 1.2%.

Figure 4.

Figure 4

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Biomechanical outcomes (ex vivo) from the cadaveric experimentation, in the axial compression test (A: contact area; B: peak contact stress; C: contact patch shift) and the sagittal-plane laxity tests (D) (n = 8, for all). The filled squares and dispersion bars indicate means and standard deviations. The X-plots in A, B, and D are individual specimens’ data. The coordinate origin of C is the contact patch centriod location for the Baseline condition.

Local peak contact stress (Figure 4B) significantly increased (from Baseline) with both MMD and TMM (p < 0.001, for both). The relative contact stress change was +56.5 ± 29.0% (range: +25 to +101%) for MMD and +59.5 ± 30.7% (+30 to +117%) for TMM. Although there was relatively large variability in individual specimen responses, the mean absolute difference of relative changes between MMD and TMM was only 7.4 ± 0.4%.

The changes in contact stress distribution associated with MMD involved significant (p = 0.001) lateral shift of the centroid of the contact patch from Baseline (0.4 ± 0.2 mm, range 0.0 to 0.7, Figure 4C). The changes with TMM also involved similar lateral shift (0.3 ± 0.2 mm, range 0.0 to 0.7, p = 0.02). Anterior-posterior shift was not significant for either MMD or TMM (p = 0.08 and 0.07, respectively).

In the sagittal-plane laxity test (Figure 3), the neutral-zone length did not exhibit significant differences across specimen conditions (Figure 4D). The relative changes from Baseline averaged +4.4 ± 15.0% (range: -15 to +36%) for MMD and +6.9 ± 21.6% (-20 to +48%) for TMM.

Survival Animal Series (In Vivo)

The histological data (Figure 5) for both the MMD and TMM groups showed significant cartilage degeneration (histological scores significantly higher than in the sham surgery group) on the medial femoral surface (p = 0.003 and 0.036, respectively), and on the medial tibial surface (p = 0.003 and 0.030, respectively). No significant differences between three conditions were identified in the lateral compartment surfaces.

Figure 5.

Figure 5

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Histological outcomes (in vivo) for each individual surface, from the survival series. Mankin scores for each individual animal are plotted, along with the mean values. The dispersion bars indicate standard deviations.

DISCUSSION

The cadaver experimental data suggest that, as originally hypothesized, medial meniscus destabilization (MMD) dramatically changes articular contact mechanics in the rabbit knee medial compartment, while leaving the whole-joint stability nearly unchanged. The histological data in the survival animal series also support the modeling concept that cumulative abnormal cartilage loading from MMD causes predictable OA development in the rabbit knees in vivo. In addition, again as hypothesized, both the biomechanical and histological effects from MMD were comparable to those from total meniscectomy.

Dysfunction of the medial meniscus has drawn increasing attention as a biomechanical factor in human knee OA. Clinical evidence20-23 suggests that a posterior root tear of the medial meniscus causes meniscal extrusion, leading to degenerative changes in the medial compartment. In a cohort study of this type of injury,24 most patients exhibited relatively rapid, progressive joint degeneration. Similarly, a murine knee survival model of medial meniscus destabilization25 (anterior root transection through an antero-medial parapatellar arthrotomy) predictably developed mild-to-moderate cartilage degeneration in the medial compartment in four weeks, primarily on the central weight-bearing regions of both the tibial plateau and femoral condyle. These observations, both in human studies and in the murine model, are very consistent with 8-week histological changes identified in the present survival rabbit series.

In the cadaver loading experiment, medial meniscus destabilization caused significant elevation (> 1.5-fold) of peak local contact stress in the medial compartment. This magnitude of stress elevation associated with surgical dysfunction of the rabbit medial meniscus is consistent with previous observations in similar cadaver loading studies of the human knee by Allaire et al.26 (> 1.25-fold increase), and of the canine knee by Pozzi et al. (> 1.4-fold increase)27 It is well recognized that an intact medial meniscus functions to distribute contact stresses relatively evenly across the medial tibio-femoral articulation.28,29 Theoretically, complete disruption of the meniscus root prevents the circumferential fibers from being able to generate hoop stresses crucial for the meniscus's contact stress equalization function.28,30 Once this hoop stress function is lost or impaired, contact stresses originally distributed to peripheral regions (normally covered by the meniscus body) are redistributed to the un-covered central region, just as demonstrated in the present compressive loading experiment (significant decrease of contact area, accompanied by significant shift of contact location toward the central tibial eminentia). Under such conditions, when the knee is subjected to physiologic loading in vivo, articular cartilage in the involved compartment presumably is exposed to cumulative abnormal loads, causing subsequent degeneration similar to that seen in the human knees after total meniscectomy.28,31,32

A limitation of the present study was that the immediate biomechanical effects of surgical insult were assessed using relatively simple quasi-static loading inputs; i.e., a compression test for contact stress and an anterior-posterior drawer test for joint stability. Although joint mechanics in vivo can be affected by variety of biomechanical factors, given that the present inputs represent the primary consideration for each respective mechanical outcome measure, arguably the experimental data reasonably characterize the biomechanical effects of interest. Computational study of cartilage internal stresses associated with superficial contact stress abnormality using a cartilage contact finite element model33 could reveal detailed mechanisms of OA development in experimental rabbit knees after MMD. Another limitation was that the cartilage degeneration resulting from surgical insult was assessed in the short term, in a relatively small series. Histological slides archived from a previous (albeit similar) study were utilized to establish control information for statistical analysis. A longer-term, larger-scale survival animal study would permit assessing further details of cartilage degeneration after medial meniscus destabilization in the rabbit knee in vivo, particularly as regards characterizing disease progression in the chronic phase. Both the biomechanical and histological evaluations presumed that the experimental joints were subjected to physiologic loading after surgical insult. Although the cadaver experimental data suggest the immediate effects on whole-joint stability to be minimal, given that rabbits confined in cages are relatively inactive, future studies should include evaluation of experimental joint usage to ensure the correlation of cartilage degeneration in experimental joints with the documented contact mechanics abnormality.

In conclusion, the present biomechanical and histological results support the medial meniscus destabilization technique as being an effective surgical insult modality to replicate injurious cumulative abnormal cartilage loading (a major biomechanical factor of post-traumatic OA) in the rabbit knee in vivo, while minimizing potential confounding effects from whole-joint instability. This rabbit knee survival model holds promise as a vehicle to study the disease mechanisms of this variant of OA, and for translational preclinical trials of new therapeutic interventions.

Acknowledgements

This research was supported by an NIH-NIAMS grant (P50 AR055533), and by grants from the US Department of Defense (W81XWH-10-1-0864 and W81XWH-11-1-0583). Neither financial sponsor had any involvement in the process of data analysis or manuscript preparation.

References

  • 1.Brown TD, Johnston RC, Saltzman CL, et al. Posttraumatic osteoarthritis: A first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20:739–744. doi: 10.1097/01.bot.0000246468.80635.ef. [DOI] [PubMed] [Google Scholar]
  • 2.Dirschl DR, Marsh JL, Buckwalter JA, et al. Articular fractures. J Am Acad Orthop Surg. 2004;12:416–423. doi: 10.5435/00124635-200411000-00006. [DOI] [PubMed] [Google Scholar]
  • 3.Buckwalter JA, Brown TD. Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis. Clin Orthop Relat Res. 2004:7–16. [PubMed] [Google Scholar]
  • 4.Anderson DD, Chubinskaya S, Guilak F, et al. Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res. 2011;29:802–809. doi: 10.1002/jor.21359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Gelber AC, Hochberg MC, Mead LA, et al. Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med. 2000;133:321–328. doi: 10.7326/0003-4819-133-5-200009050-00007. [DOI] [PubMed] [Google Scholar]
  • 6.Anderson DD, Van Hofwegen C, Marsh JL, Brown TD. Is elevated contact stress predictive of post-traumatic osteoarthritis for imprecisely reduced tibial plafond fractures? J Orthop Res. 2011;29:33–39. doi: 10.1002/jor.21202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Aigner T, Cook JL, Gerwin N, et al. Histopathology atlas of animal model systems - overview of guiding principles. Osteoarthritis Cartilage 18 Suppl. 2010;3:S2–6. doi: 10.1016/j.joca.2010.07.013. [DOI] [PubMed] [Google Scholar]
  • 8.Messner K, Fahlgren A, Persliden J, Andersson BM. Radiographic joint space narrowing and histologic changes in a rabbit meniscectomy model of early knee osteoarthrosis. Am J Sports Med. 2001;29:151–160. doi: 10.1177/03635465010290020701. [DOI] [PubMed] [Google Scholar]
  • 9.Brophy RH, Martinez M, Borrelli J, Jr., Silva MJ. Effect of combined traumatic impact and radial transection of medial meniscus on knee articular cartilage in a rabbit in vivo model. Arthroscopy. 2012;28:1490–1496. doi: 10.1016/j.arthro.2012.03.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Vaseenon T, Tochigi Y, Heiner AD, et al. Organ-level histological and biomechanical responses from localized osteoarticular injury in the rabbit knee. J Orthop Res. 2011;29:340–346. doi: 10.1002/jor.21259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Borrelli J, Jr., Silva MJ, Zaegel MA, et al. Single high-energy impact load causes posttraumatic OA in young rabbits via a decrease in cellular metabolism. J Orthop Res. 2009;27:347–352. doi: 10.1002/jor.20760. [DOI] [PubMed] [Google Scholar]
  • 12.Brophy RH, Martinez M, Borrelli J, Jr., Silva MJ. Effect of combined traumatic impact and radial transection of medial meniscus on knee articular cartilage in a rabbit in vivo model. Arthroscopy. 2012;28:1490–1496. doi: 10.1016/j.arthro.2012.03.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Lyalka VF, Orlovsky GN, Deliagina TG. Impairment of postural control in rabbits with extensive spinal lesions. J Neurophysiol. 2009;101:1932–1940. doi: 10.1152/jn.00009.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Mansour JM, Wentorf FA, Degoede KM. In vivo kinematics of the rabbit knee in unstable models of osteoarthrosis. Annals of biomedical engineering. 1998;26:353–360. doi: 10.1114/1.133. [DOI] [PubMed] [Google Scholar]
  • 15.Gushue DL, Houck J, Lerner AL. Rabbit knee joint biomechanics: motion analysis and modeling of forces during hopping. J Orthop Res. 2005;23:735–742. doi: 10.1016/j.orthres.2005.01.005. [DOI] [PubMed] [Google Scholar]
  • 16.Heiner AD, Rudert MJ, McKinley TO, et al. In vivo measurement of translational stiffness of rabbit knees. J Biomech. 2007;40:2313–2317. doi: 10.1016/j.jbiomech.2006.10.036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Laverty S, Girard CA, Williams JM, et al. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthritis Cartilage 18 Suppl. 2010;3:S53–65. doi: 10.1016/j.joca.2010.05.029. [DOI] [PubMed] [Google Scholar]
  • 18.Tochigi Y, Vaseenon T, Heiner AD, et al. Instability dependency of osteoarthritis development in a rabbit model of graded anterior cruciate ligament transection. J Bone Joint Surg Am. 2011;93:640–647. doi: 10.2106/JBJS.J.00150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Moussavi-Harami SF, Pedersen DR, Martin JA, et al. Automated objective scoring of histologically apparent cartilage degeneration using a custom image analysis program. J Orthop Res. 2009;27:522–528. doi: 10.1002/jor.20779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Jones AO, Houang MT, Low RS, Wood DG. Medial meniscus posterior root attachment injury and degeneration: MRI findings. Australas Radiol. 2006;50:306–313. doi: 10.1111/j.1440-1673.2006.01586.x. [DOI] [PubMed] [Google Scholar]
  • 21.Lerer DB, Umans HR, Hu MX, Jones MH. The role of meniscal root pathology and radial meniscal tear in medial meniscal extrusion. Skeletal Radiol. 2004;33:569–574. doi: 10.1007/s00256-004-0761-2. [DOI] [PubMed] [Google Scholar]
  • 22.Adams JG, McAlindon T, Dimasi M, et al. Contribution of meniscal extrusion and cartilage loss to joint space narrowing in osteoarthritis. Clin Radiol. 1999;54:502–506. doi: 10.1016/s0009-9260(99)90846-2. [DOI] [PubMed] [Google Scholar]
  • 23.Gale DR, Chaisson CE, Totterman SM, et al. Meniscal subluxation: association with osteoarthritis and joint space narrowing. Osteoarthritis Cartilage. 1999;7:526–532. doi: 10.1053/joca.1999.0256. [DOI] [PubMed] [Google Scholar]
  • 24.Beasley L, Armfield RD, West R, et al. Medial meniscus root tears: an unsolved problem-demographic, radiographic, and arthroscopic findings. Pittsburg Orthop J. 2005;16 [Google Scholar]
  • 25.Glasson SS, Blanchet TJ, Morris EA. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis Cartilage. 2007;15:1061–1069. doi: 10.1016/j.joca.2007.03.006. [DOI] [PubMed] [Google Scholar]
  • 26.Allaire R, Muriuki M, Gilbertson L, Harner CD. Biomechanical consequences of a tear of the posterior root of the medial meniscus. Similar to total meniscectomy. J Bone Joint Surg Am. 2008;90:1922–1931. doi: 10.2106/JBJS.G.00748. [DOI] [PubMed] [Google Scholar]
  • 27.Pozzi A, Kim SE, Lewis DD. Effect of transection of the caudal menisco-tibial ligament on medial femorotibial contact mechanics. Vet Surg. 2010;39:489–495. doi: 10.1111/j.1532-950X.2010.00662.x. [DOI] [PubMed] [Google Scholar]
  • 28.Radin EL, de Lamotte F, Maquet P. Role of the menisci in the distribution of stress in the knee. Clin Orthop Relat Res. 1984:290–294. [PubMed] [Google Scholar]
  • 29.Kurosawa H, Fukubayashi T, Nakajima H. Load-bearing mode of the knee joint: physical behavior of the knee joint with or without menisci. Clin Orthop Relat Res. 1980:283–290. [PubMed] [Google Scholar]
  • 30.Fairbank TJ. Knee joint changes after meniscectomy. J Bone Joint Surg Br. 1948;30B:664–670. [PubMed] [Google Scholar]
  • 31.Krause WR, Pope MH, Johnson RJ, Wilder DG. Mechanical changes in the knee after meniscectomy. J Bone Joint Surg Am. 1976;58:599–604. [PubMed] [Google Scholar]
  • 32.Hede A, Larsen E, Sandberg H. The long term outcome of open total and partial meniscectomy related to the quantity and site of the meniscus removed. Int Orthop. 1992;16:122–125. doi: 10.1007/BF00180200. [DOI] [PubMed] [Google Scholar]
  • 33.Goreham-Voss CM, McKinley TO, Brown TD. Finite element exploration of cartilage stress near an articular incongruity during unstable motion. J Biomech. 2007;40:3438–3447. doi: 10.1016/j.jbiomech.2007.05.023. [DOI] [PMC free article] [PubMed] [Google Scholar]

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