Preliminary identification of somatic mutations profile in ACL injury.

Anterior cruciate ligament (ACL) injury is a common orthopedic disease with a high incidence, long recovery time, and often requiring surgical treatment. However, the susceptibility factors for ACL injury are currently unclear, and there is a lack of analysis on the differences in the ligament itself. Previous studies have focused on germline mutations, with less research on somatic mutations. To determine the role of somatic mutations in ACL injuries, we recruited seven patients between the ages of 20 and 39 years diagnosed with ACL injuries, collected their peripheral blood, injured ligament ends, and healthy ligament ends tissues, and performed exome sequencing with gene function enrichment analysis. We detected multiple gene mutations and gene deletions, which were only present in some of the samples. Unfortunately, it was not possible to determine whether these somatic mutations are related to ligament structure or function, or are involved in ACL injury. However, this study provides valuable clues for future in-depth research.

Increased vascular endothelial growth factor expression is associated with cruciate ligament degeneration in patients with osteoarthritis of the knee.

BACKGROUND: This study aimed to investigate the expression of vascular endothelial growth factor (VEGF) in cruciate ligaments from patients with osteoarthritis (OA). It was hypothesized that the expression level of VEGF is associated with the extent of degeneration of the cruciate ligaments. METHODS: Remnants of anterior cruciate ligaments (ACLs) from patients with acute ACL injury due to trauma, and ACLs and posterior cruciate ligaments (PCLs) from patients with primary OA were assessed histologically. Samples were immunohistochemically stained with VEGF and tenomodulin, and immunopositive cells were quantitatively assessed by the histological grades of ligament degeneration. RESULTS: Histological analysis showed significant degeneration of the ACLs from OA patients compared with trauma patients, with increased expression of VEGF correlating with higher grades of degeneration. Conversely, tenomodulin expression was lower in more degenerated cruciate ligaments. The percentage of VEGF-positive cells was correlated inversely with that of tenomodulin-positive cells. CONCLUSIONS: Increased VEGF expression is associated with degeneration of cruciate ligaments in patients with osteoarthritis of the knee.

Deep Learning-Assisted Automatic Diagnosis of Anterior Cruciate Ligament Tear in Knee Magnetic Resonance Images.

Anterior cruciate ligament (ACL) tears are prevalent knee injures, particularly among active individuals. Accurate and timely diagnosis is essential for determining the optimal treatment strategy and assessing patient prognosis. Various previous studies have demonstrated the successful application of deep learning techniques in the field of medical image analysis. This study aimed to develop a deep learning model for detecting ACL tears in knee magnetic resonance Imaging (MRI) to enhance diagnostic accuracy and efficiency. The proposed model consists of three main modules: a Dual-Scale Data Augmentation module (DDA) to enrich the training data on both the spatial and layer scales; a selective group attention module (SG) to capture relationships across the layer, channel, and space scales; and a fusion module to explore the inter-relationships among various perspectives to achieve the final classification. To ensure a fair comparison, the study utilized a public dataset from MRNet, comprising knee MRI scans from 1250 exams, with a focus on three distinct views: axial, coronal, and sagittal. The experimental results demonstrate the superior performance of the proposed model, termed SGNET, in ACL tear detection compared with other comparison models, achieving an accuracy of 0.9250, a sensitivity of 0.9259, a specificity of 0.9242, and an AUC of 0.9747.

Do the Clinical and Radiological Features of Knees with Mucoid Degeneration of the Anterior Cruciate Ligament Differ According to Knee Osteoarthritis Status?

Background: The etiology and pathology of mucoid degeneration of the anterior cruciate ligament (MD-ACL) remain poorly understood. MD-ACL may be associated with knee osteoarthritis (OA) or a mechanism other than OA. This study evaluated the radiological differences between knees with MD-ACL and those with a normal ACL and compared the clinical and radiological features of knees with MD-ACL according to the knee OA status. Methods: This retrospective study compared the radiological features of the intercondylar notch width index (NWI) and posterior tibial slope (PTS) of 67 MD-ACL patients (MD group) and 67 age-, sex-, and OA grade-matched patients with a normal ACL (control group). During the subgroup analysis, MD-ACL patients were divided into the non-OA subgroup (n = 41) and OA subgroup (n = 26). The pain location and characteristics of the knee, PTS, and NWI were compared between these subgroups. Results: Compared to the control group, the MD group had a lower NWI (0.26 ± 0.03 vs. 0.28 ± 0.01, p < 0.001) and a larger PTS (11.3° ± 3.0° vs. 9.2° ± 2.5°, p < 0.001). During the subgroup analysis, the most common pain locations were the posterior and medial aspects of the knee in the non-OA subgroup (43.9%) and OA subgroup (53.8%), respectively. Pain on terminal flexion was the most common pain characteristic in both subgroups (non-OA subgroup, 73.1%; OA subgroup, 53.8%). The PTS was not different between subgroups (11.7° ± 3.2° in the non-OA subgroup vs. 10.6° ± 2.7° in the OA subgroup; p = 0.159). However, the non-OA subgroup had a lower NWI than the OA subgroup (0.25 ± 0.03 vs. 0.28 ± 0.02, p = 0.001). Conclusions: Patients with MD-ACL had a lower NWI and a larger PTS than patients with a normal ACL. Furthermore, the clinical and radiological features of MD-ACL differed according to the knee OA status. A narrow intercondylar notch may be more closely associated with the development of MD-ACL without OA.

Effects of sex differences on osteoarthritic changes after anterior cruciate ligament reconstruction in rats.

The prevalence of primary osteoarthritis is higher in females than males. However, it remains unclear if there are sex differences in the incidence of post-traumatic osteoarthritis after anterior cruciate ligament (ACL) reconstruction. In this study, we aimed to investigate the effects of sex on osteoarthritic changes after ACL reconstruction using an animal model. Rats were divided into the following four groups: male control, male ACL reconstruction, female control, and female ACL reconstruction. ACL reconstruction surgery was performed on the right knees of rats in the ACL reconstruction groups, while rats in the control groups did not undergo knee surgery. At 1, 4, and 12 weeks after surgery, cartilage degeneration in the medial tibial plateau and osteophyte formation in the proximal tibia were histologically assessed. After ACL reconstruction, an increase in the Mankin score, cartilage fissures, and osteophyte formation were detected within 12 weeks in both male and female rats, with similar degrees of these changes between males and females. However, changes in cartilage thickness and chondrocyte density after ACL reconstruction differed between males and females. Cartilage thickening was observed in male rats but not in female rats. The increase in chondrocyte density in the anterior region was detected in both males and females but was more pronounced in female rats. In conclusion, osteoarthritic changes were observed after ACL reconstruction in both male and female rats, but differences in changes in cartilage thickness and chondrocyte density were observed between males and females.

Evaluation of tendon and ligament microstructure and mechanical properties in a canine model of mucopolysaccharidosis I.

Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder characterized by deficient alpha-l-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a strong clinical need for improved treatment approaches that specifically target joint tissues; however, their development is hampered by poor understanding of underlying disease pathophysiology, including how pathological changes to component tissues contribute to overall joint dysfunction. Ligaments and tendons, in particular, have received very little attention, despite the critical roles of these tissues in joint stability and biomechanical function. The goal of this study was to leverage the naturally canine model to undertake functional and structural assessments of the anterior (cranial) cruciate ligament (CCL) and Achilles tendon in MPS I. Tissues were obtained postmortem from 12-month-old MPS I and control dogs and tested to failure in uniaxial tension. Both CCLs and Achilles tendons from MPS I animals exhibited significantly lower stiffness and failure properties compared to those from healthy controls. Histological examination revealed multiple pathological abnormalities, including collagen fiber disorganization, increased cellularity and vascularity, and elevated GAG content in both tissues. Clinically, animals exhibited mobility deficits, including abnormal gait, which was associated with hyperextensibility of the stifle and hock joints. These findings demonstrate that pathological changes to both ligaments and tendons contribute to abnormal joint function in MPS I, and suggest that effective clinical management of joint disease in patients should incorporate treatments targeting these tissues.

The effects of tibial tuberosity avulsion and repair on tibial plateau angle in dogs.

AIMS: To assess whether tibial tuberosity avulsion injury and subsequent surgical repair in skeletally immature dogs are associated with changes in tibial plateau angle (TPA) at skeletal maturity. METHODS: Skeletally mature (> 18 months of age) dogs that had previously undergone unilateral surgery when 4-8 months of age to repair tibial tuberosity avulsion were enrolled. Bilateral, mediolateral stifle radiographs were taken. TPA was measured digitally from the radiographs independently by two readers and compared between sides within dogs. As the number of dogs that would be enrolled for the main part of the study was unknown, to understand how the variation between left and right stifles within dogs would affect the power of the main study, 29 client-owned, skeletally mature dogs without stifle pathology were recruited prior to the main study for bilateral, mediolateral projection stifle radiographs. Variation in the differences in TPA between left and right stifles was used to estimate the likely power of the major part of the study for different numbers of enrolled dogs. RESULTS: From 29 dogs enrolled in the power assessment, the SD of the differences between left and right stifles was 2.1°. With 10 dogs (20 stifles) enrolled within the main part of the study, and if the SD of the differences between operated and non-operated stifles within a dog was the same as the SD of the differences between non-operated stifles within a dog (2.1°), the study would have power ≥ 0.8 if the mean difference in TPA between operated and non-operated stifles was ≥ 2.1°.Ten dogs were enrolled in phase II of the study. In 8/10 of these dogs, the TPA in the operated stifle was less than in the non-operated stifle. The mean TPA on the operated stifle was 6.4° less than on the non-operated stifle (95% CI = 2.4-10.3° less; p = 0.002). For surgery between 4 and 8 months of age, TPA at maturity increased by 2.7° (95% CI = 1.1-4.3°; p = 0.001) for each additional month of age at surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Based on this study, surgical repair of tibial tuberosity avulsion in skeletally immature dogs is associated with a smaller TPA at skeletal maturity. However, causality cannot be established from this cross-sectional study, and this association may be because stifles with a smaller TPA are predisposed to tibial tuberosity avulsion.

Diagnostic Accuracy of Candidate Magnetic Resonance Imaging Knee Osteoarthritis Definitions Versus Radiograph in an Acute Anterior Cruciate Ligament Injury Cohort.

OBJECTIVE: We tested the diagnostic accuracy of previously proposed magnetic resonance imaging (MRI) osteoarthritis (OA) definitions in a cohort after acute anterior cruciate ligament (ACL) injury. METHODS: We studied participants with posteroanterior and lateral knee radiographs and MRI 5 years after ACL injury, scored using the Anterior Cruciate Ligament Osteoarthritis Score. Radiographic OA (ROA) was defined using Osteoarthritis Research Society International scoring of osteophytes and joint space narrowing considering medial/lateral tibiofemoral and patellofemoral compartments. We tested three candidate MRI OA definitions that performed well in an older adult cohort. "Multicenter Osteoarthritis Study (MOST) simple" required cartilage score ≥2 (range 0-6) and osteophyte score ≥2 (0-7); "MOST optional" included cartilage score ≥2, osteophyte score ≥2, and either bone marrow lesions (BMLs) ≥1 (0-3) or synovitis ≥2 (0-3). The third, a Delphi panel definition, included nonzero scores for cartilage, osteophyte, BMLs, meniscus, and other structures. We calculated sensitivity and specificity with 95% confidence intervals (95% CIs) for each MRI definition versus ROA. RESULTS: We included 113 participants (mean age 26 years, 26% female). At 5 years, 29 participants (26%) had ROA. "MOST simple" had a sensitivity of 52% (95% CI 33%-71%), and specificity of 76% (95% CI 66%-85%). Sensitivity and specificities for "MOST optional" were 28% (95% CI 29%-67%) and 83% (95% CI 74%-91%), respectively. The Delphi panel definition had a sensitivity of 48% (95% CI 29%-67%) and specificity of 77% (95% CI 67%-86%). CONCLUSION: Simple MRI-based OA definitions requiring at least cartilage damage and an osteophyte have low sensitivity and high specificity in young persons after knee injury.

Determining predictive metabolomic biomarkers of meniscal injury in dogs with cranial cruciate ligament rupture.

OBJECTIVES: This study used hydrogen nuclear magnetic resonance spectroscopy for the first time to examine differences in the metabolomic profile of stifle joint synovial fluid from dogs with cranial cruciate ligament rupture with and without meniscal injuries, in order to identify biomarkers of meniscal injury. Identifying a biomarker of meniscal injury could then ultimately be used to design a minimally invasive diagnostic test for meniscal injuries in dogs. MATERIALS AND METHODS: Stifle joint synovial fluid was collected from dogs undergoing stifle joint surgery or arthrocentesis for lameness investigations. We used multi-variate statistical analysis using principal component analysis and univariate statistical analysis using one-way analysis of variance and analysis of co-variance to identify differences in the metabolomic profile between dogs with cranial cruciate ligament rupture and meniscal injury, cranial cruciate ligament rupture without meniscal injury, and neither cranial cruciate ligament rupture nor meniscal injury, taking into consideration clinical variables. RESULTS: A total of 154 samples of canine synovial fluid were included in the study. Sixty-four metabolites were annotated to the hydrogen nuclear magnetic resonance spectroscopy spectra. Six spectral regions were found to be significantly altered (false discovery rate adjusted P-value <0.05) between groups with cranial cruciate ligament rupture with and without meniscal injury, including three attributed to nuclear magnetic resonance mobile lipids [mobile lipid -CH3 (P=0.016), mobile lipid -n(CH3 )3 (P=0.017), mobile unsaturated lipid (P=0.031)]. CLINICAL SIGNIFICANCE: We identified an increase in nuclear magnetic resonance mobile lipids in the synovial fluid of dogs with meniscal injury which are of interest as potential biomarkers of meniscal injury.

Intercondylar Notch Pathology.

The intercondylar notch of the knee is a relatively small area. However, numerous rare pathologies can arise in this region. A majority of the existing literature has focused on the cruciate ligament injuries, yet there are several other entities that can cause knee pain from within the intercondylar notch. This review focuses on identifying the various diagnostic and treatment options for rare benign and malignant lesions including ganglion cyst formation, mucoid degeneration, benign proliferative conditions, and intra-articular tumors. These entities are most often diagnosed with advanced imaging studies and treated arthroscopically. While rare, these pathologies are important to identify in patients with ongoing vague knee pain.

A single-cell atlas depicting the cellular and molecular features in human anterior cruciate ligamental degeneration: A single cell combined spatial transcriptomics study.

Background: To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression. Methods: Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49,356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes' spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining. Results: We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease. Conclusions: This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies. Funding: This study was funded by the National Natural Science Foundation of China (81972123, 82172508, 82372490) and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).

Arthroscopic Debridement for Mucoid Degeneration of Anterior Cruciate Ligament - A Single Institution Experience from Nepal.

Background Mucoid degeneration of anterior cruciate ligament is characterized by infiltration of mucoid-like material scattered throughout the anterior cruciate ligament substance. It is an uncommon condition, but previously, underdiagnosed or often misdiagnosed as an anterior cruciate ligament tear. Objective To present our early experiences with mucoid degeneration of anterior cruciate ligament in last five years in terms of clinical presentation and the outcomes of arthroscopic management. Method This was a retrospective descriptive cross-sectional study on patient who received arthroscopic debridement for mucoid degeneration of anterior cruciate ligament in Dhulikhel Hospital over five years period (2017 May to 2022 April). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale that has been translated and validated to be used in local (Nepali) language and context was used for evaluation of outcome evaluation. Result Twenty-one patients of mean age 44.21 years, predominantly females (18), were managed in five years period. The mean Western Ontario and McMaster Universities Osteoarthritis Index score was 16.33±10.47 with a range of 0 to 36 (11.57 to 21.09 at 95% confidence interval). The mean Western Ontario and McMaster Universities Osteoarthritis Index score converted on a scale of 0 to 100 was 17. Thirteen patients had isolated Mucoid degeneration of anterior cruciate ligament whereas nine others had associated either meniscal tear or chondral lesions. Conclusion Mucoid degeneration of anterior cruciate ligament could be a cause of knee pain in middle-aged patients and arthroscopic debridement can improve the patient's symptoms and provide a good functional outcome.

Effects of SKCPT on Osteoarthritis in Beagle Meniscectomy and Cranial Cruciate Ligament Transection Models.

Osteoarthritis (OA) affects >500 million people globally, and this number is expected to increase. OA management primarily focuses on symptom alleviation, using non-steroidal anti-inflammatory drugs, including Celecoxib. However, such medication has serious side effects, emphasizing the need for disease-specific treatment. The meniscectomy and cranial cruciate ligament transection (CCLx)-treated beagle dog was used to investigate the efficacy of a modified-release formulation of SKI306X (SKCPT) from Clematis mandshurica, Prunella vulgaris, and Trichosanthes kirilowii in managing arthritis. SKCPT's anti-inflammatory and analgesic properties have been assessed via stifle circumference, gait, incapacitance, histopathology, and ELISA tests. The different SKCPT concentrations and formulations also affected the outcome. SKCPT improved the gait, histopathological, and ELISA OA assessment parameters compared to the control group. Pro-inflammatory cytokines and matrix metalloproteinases were significantly lower in the SKCPT-treated groups than in the control group. This study found that SKCPT reduces arthritic lesions and improves abnormal gait. The 300 mg modified-release formulation was more efficacious than others, suggesting a promising approach for managing OA symptoms and addressing disease pathogenesis. A high active ingredient level and a release pattern make this formulation effective for twice-daily arthritis treatment.

Computed tomographic imaging and surgical management of distal insertional avulsion fragments of the caudal cruciate ligament in four horses.

OBJECTIVE: To describe cases with caudal cruciate ligament (CdCL) avulsion fragments diagnosed based on computed tomography (CT) examination and report on arthroscopic fragment removal. ANIMALS: Four Warmblood horses with hindlimb lameness and osseous fragments located in the caudal medial femorotibial joint (mFTJ). STUDY DESIGN: Short case series. METHODS: CT and arthroscopic evaluation of the caudal mFTJ were performed. The caudal mFTJ and the insertion of the CdCL on the tibia were assessed and removal of the avulsion fragments was attempted in three horses using a cranial intercondylar approach. RESULTS: The fragment was not accessible via caudomedial approaches in one horse. A cranial intercondylar approach was used in three horses, allowing removal of the intra-articular fragment in two horses, and removal of two-thirds of the proximal fragment in the last horse. Acute, profuse, arterial bleeding occurred in this horse during surgery with transient postoperative soft tissue swelling. Comorbidities included medial femoral condyle cartilage defects (3), cranial cruciate ligament lesions (2), and medial collateral ligament lesions (2). Horses were followed up for 16 months (median, range 11-28 months), at which point all were back in ridden exercise; owners' satisfaction was good. CONCLUSION: CT examination confirmed the diagnosis and allowed evaluation of the stifle joint for comorbidities. A cranial intercondylar arthroscopic approach facilitated the removal of CdCL insertional avulsion fragments, although not always complete. CLINICAL SIGNIFICANCE: A cranial intercondylar approach can allow access to CdCL avulsion fragments, but complications and incomplete removal remain possible.

Growth progression of anterior cruciate ligament bone grafts in a pediatric population: magnetic resonance imaging analysis.

BACKGROUND: In children, the incidence of anterior cruciate ligament (ACL) ruptures and reconstructions has significantly risen. Unfortunately, re-rupture rates following surgery are substantially higher in children than adults. Previous research suggests that smaller graft diameters are predictive of re-rupture. OBJECTIVE: This study aimed to investigate the growth progression of the ACL bone graft, specifically in terms of width and length, within the intra-articular portion and tunnels, using successive magnetic resonance imaging (MRI) scans. The hypothesis was that the ACL grafts would undergo thinning during growth. MATERIALS AND METHODS: The cohort comprised 100 patients who underwent ACL reconstruction. Among them, 37 patients with significant residual growth were selected for analysis. Of these, 4 patients experienced graft rupture, 5 had "over-the-top" techniques, 12 had missing MRI scans and 5 were lost to follow-up. Each included patient underwent two MRI scans; the analyses of which were conducted in a double-masked manner. RESULTS: A total of 13 knees (and patients) were analyzed, with a mean ± SD (range) delay of residual growth between the two MRI scans of 3.3 + / - 1.4 (1.2-5.2) years. The graft exhibited elongation, thinning and eventual integration with the surrounding bone in the tunnels. Within the intra-articular portion, the mean [95% CI] increase in graft size between the two MRI scans was 30.8% in length and 14.8% in width. The width/length ratio in the intra-articular part was 20.4% on the first MRI and 20.8% on the second MRI. Since this difference in the ratio (+ 0.4%) was not statistically significant (P=0.425), our results indicate that the grafts remained stable in terms of proportions without thinning or thickening. Therefore, the initial hypothesis was validated for the tunnel portion but not the intra-articular portion of the grafts. CONCLUSION: In children with open physes, ACL grafts demonstrate smooth growth progression in all dimensions. However, this finding does not fully explain the high rate of re-rupture observed in children. Further research is needed to elucidate the underlying factors contributing to re-rupture in this population.

What it takes to have a high-grade pivot shift-focus on bony morphology.

PURPOSE: Variations in femoral and tibial bony morphology have been associated with higher clinical grading and increased quantitative tibial translation, but not tibial acceleration, during the pivot shift test following anterior cruciate ligament (ACL) injury. The purpose of this study was to determine the impact of femoral and tibial bony morphology, including a measurement influenced by both parameters (the Lateral Tibiofemoral Articular Distance (LTAD)), on the degree of quantitative tibial acceleration during the pivot shift test and rates of future ACL injury. METHODS: All patients who underwent primary ACL reconstruction from 2014 to 2019 by a senior orthopedic surgeon with available quantitative tibial acceleration data were retrospectively reviewed. All patients underwent a pivot shift examination under anesthesia with a triaxial accelerometer. Measurements of femoral and tibial bony morphology were performed by two fellowship-trained orthopedic surgeons using preoperative magnetic resonance imaging and lateral radiographs. RESULTS: Fifty-one patients were included at a mean follow-up of 4.4 years. The mean quantitative tibial acceleration during the pivot shift was 13.8 m/s2 (range: 4.9-52.0 m/s2). A larger Posterior Condylar Offset Ratio (r = 0.30, p = 0.045), smaller medial-to-lateral width of the medial tibial plateau (r = - 0.29, p = 0.041), lateral tibial plateau (r = - 0.28, p = 0.042), and lateral femoral condyle (r = - 0.29, p = 0.037), and a decreased LTAD (r = - 0.53, p < 0.001) significantly correlated with increased tibial acceleration during the pivot shift. Linear regression analysis demonstrated an increase in tibial acceleration of 1.24 m/s2 for every 1 mm decrease in LTAD. Nine patients (17.6%) sustained ipsilateral graft rupture and 10 patients (19.6%) sustained contralateral ACL rupture. No morphologic measurements were associated with rates of future ACL injury. CONCLUSION: Increased convexity and smaller bony morphology of the lateral femur and tibia were significantly associated with increased tibial acceleration during the pivot shift. Additionally, a measurement, termed the LTAD, was found to have the strongest association with increased tibial acceleration. Based on the results of this study, surgeons can utilize these measurements to preoperatively identify patients at risk of increased rotatory knee instability. LEVEL OF EVIDENCE: Level IV.

Regional Alterations of Macroscopy and Histology in Meniscus in an ACL Transection Rabbit Model.

BACKGROUND: Although meniscal injury is common after anterior cruciate ligament (ACL) injury, the underlying process in different meniscal regions remains unclear. PURPOSE: To investigate macroscopic and histological alterations in different meniscal regions in an ACL transection (ACLT) rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: ACLT was performed on New Zealand White rabbits. Both the medial meniscus (MM) and the lateral meniscus (LM) of the ACLT knees were obtained at 8 (n = 6) and 26 (n = 6) weeks postoperatively. MM and LM collected from nonoperated knees were considered 0 weeks (n = 6) postoperatively. Menisci were then divided into posterior, central, and anterior regions for macroscopic (width) and histological (hematoxylin and eosin, safranin O/fast green, collagen type 2 [COL2]) analysis. RESULTS: The macroscopic widths of MM and LM increased and then decreased over 26 weeks postoperatively, with all 3 MM widths at 8 weeks significantly wider than at 0 weeks (posterior: P < .01; central: P < .05; anterior: P < .05). In the MM, chondrocyte-like cell density increased and then decreased postoperatively, whereas in the LM, it decreased and then remained almost unchanged. Cell density was significantly higher in the central MM region at 8 weeks than at 0 weeks (P < .05). Glycosaminoglycan (GAG) and COL2 percentages of MM and LM decreased from 0 to 8 weeks and then returned to nearly normal levels at 26 weeks postoperatively. In the MM, the GAG percentage in the posterior (P < .05) and central (P < .01) regions and the COL2 percentage in the posterior region (P < .05) was significantly lower at 8 weeks than at 0 weeks. CONCLUSION: After ACLT in rabbit meniscus, the extracellular matrix (ECM) initially decreased and then increased to almost normal. Additionally, there were significant differences in the ECM percentage in the posterior and central regions of the MM in comparison with other meniscal regions between 0 and 8 weeks postoperatively. CLINICAL RELEVANCE: The results indicate that the time for meniscal injury after ACL injury is important, and attention should be paid to the posterior and central regions of the MM after ACLT.

Femoral condyle configuration and its impact on anterior cruciate ligament reconstruction.

BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is one of the most common knee injuries and has substantial impact on knee function. Beside primary ruptures, an increasing number of re-(re-)ruptures occur, representing a therapeutical challenge for the treating surgeon. Several risk factors for re-ruptures have been previously identified, including an increased tibial slope. OBJECTIVE: In this study, we investigated the effect of femoral condyle configuration on ACL-ruptures and re-ruptures. METHODS: In-vivo magnetic resonance imaging scans of three different groups of patients were compared. Group 1 included patients with an intact ACL on both sides, group 2 included patients with primary, unilateral ACL-rupture, while group 3 included patients with an ACL-re-rupture or re-(re-)rupture. Fourteen different variables were obtained and analyzed regarding their impact on ACL-re-(re-)rupture. RESULTS: Overall, 334 knees were investigated. Our data allowed us to define parameters to identify anatomical configurations of bones associated with an increased risk of ACL-re-rupture. Our results show, that patients with ACL-re-rupture show increased radii of the extension facet of the lateral femoral condyle (p< 0.001) as well as of the extension facet of the medial femoral condyle (p< 0.001). CONCLUSION: We conclude that a spherical femoral condyle form does influence the clinical outcome after ACL-reconstruction.

Functional Loss of Terminal Complement Complex Protects Rabbits from Injury-Induced Osteoarthritis on Structural and Cellular Level.

The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related tissues using a rabbit PTOA model. In brief, a C6-deficient rabbit breed was characterized on genetic, protein, and functional levels. Anterior cruciate ligament transection (ACLT) was performed in C6-deficient (C6-/-) and C6-sufficient (C6+/-) rabbits. After eight weeks, the progression of PTOA was determined histologically. Moreover, the structure of the subchondral bone was evaluated by µCT analysis. C6 deficiency could be attributed to a homozygous 3.6 kb deletion within the C6 gene and subsequent loss of the C5b binding site. Serum from C6-/- animals revealed no hemolytic activity. After ACLT surgery, joints of C6-/- rabbits exhibited significantly lower OA scores, including reduced cartilage damage, hypocellularity, cluster formation, and osteophyte number, as well as lower chondrocyte apoptosis rates and synovial prostaglandin E2 levels. Moreover, ACLT surgery significantly decreased the trabecular number in the subchondral bone of C6-/- rabbits. Overall, the absence of TCC protected from injury-induced OA progression but had minor effects on the micro-structure of the subchondral bone.