scholarly journals Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice

2021 ◽  
Vol 10 (18) ◽  
pp. 4051
Author(s):  
Shin Fukusato ◽  
Masashi Nagao ◽  
Kei Fujihara ◽  
Taiju Yoneda ◽  
Kiyotaka Arai ◽  
...  

Anterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures, 100% functional recovery is unlikely. Therefore, the discovery of risk factors for ACL ruptures may prevent injury. Several studies have reported an association between polymorphisms of the collagen XII gene COL12A1 and ACL rupture. Collagen XII is highly expressed in tendons and ligaments and regulates tissue structure and mechanical property. Therefore, we hypothesized that collagen XII deficiency may cause ACL injury. To elucidate the influence of collagen XII deficiency on ACL, we analyzed a mouse model deficient for Col12a1. Four- to 19-week-old male Col12a1-/- and wild-type control mice were used for gait analysis; histological and immunofluorescent analysis of collagen XII, and real-time RT-PCR evaluation of Col12a1 mRNA expression. The Col12a1-/- mice showed an abnormal gait with an approximately 2.7-fold increase in step angle, suggesting altered step alignment. Col12a1-/- mice displayed 20–60% ACL discontinuities, but 0% discontinuity in the posterior cruciate ligament. No discontinuities in knee ligaments were found in wild-type mice. Collagen XII mRNA expression in the ACL tended to decrease with aging. Our study demonstrates for the first time that collagen XII deficiency increases the risk of ACL injury.

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
David Simon ◽  
Randy Mascarenhas ◽  
Bryan M. Saltzman ◽  
Meaghan Rollins ◽  
Bernard R. Bach ◽  
...  

Anterior cruciate ligament (ACL) tears are a common injury, particularly in the athletic and youth populations. The known association between ACL injury and subsequent osteoarthritis (OA) of the knee merits a more in-depth understanding of the relationship between the ACL-injured knee and osteoarthritis. ACL injury, especially with concomitant meniscal or other ligamentous pathology, predisposes the knee to an increased risk of osteoarthritis. ACL insufficiency results in deterioration of the normal physiologic knee bending culminating in increased anterior tibial translation and increased internal tibial rotation. This leads to increased mean contact stresses in the posterior medial and lateral compartments under anterior and rotational loading. However, surgical reconstruction of the ACL has not been shown to reduce the risk of future OA development back to baseline and has variability based on operative factors of graft choice, timing of surgery, presence of meniscal and chondral abnormalities, and surgical technique. Known strategies to prevent OA development are applicable to patients with ACL deficiency or after ACL reconstruction and include weight management, avoidance of excessive musculoskeletal loading, and strength training. Reconstruction of the ACL does not necessarily prevent osteoarthritis in many of these patients and may depend on several external variables.


2018 ◽  
Vol 47 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Einar Andreas Sivertsen ◽  
Kari Bente Foss Haug ◽  
Eirik Klami Kristianslund ◽  
Anne-Marie Siebke Trøseid ◽  
Jari Parkkari ◽  
...  

Background: Several single-nucleotide variants (SNVs) in collagen genes have been reported as predisposing factors for anterior cruciate ligament (ACL) tears. However, the evidence is conflicting and does not support a clear association between genetic variants and risk of ACL ruptures. Purpose: To assess the association of previously identified candidate SNVs in genes encoding for collagen and the risk of ACL injury in a population of elite female athletes from high-risk team sports. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 851 female Norwegian and Finnish elite athletes from team sports were included from 2007 to 2011. ACL injuries acquired before inclusion in the cohort were registered by interview. The participants were followed prospectively through 2015 to record new complete ACL injuries. Six selected SNVs were genotyped ( COL1A1: rs1800012, rs1107946; COL3A1: rs1800255; COL5A1: rs12722, rs13946; COL12A1: rs970547). Results: No associations were found between ACL rupture and the SNVs tested. Conclusion: The study does not support a role of the 6 selected SNVs in genes encoding for collagen proteins as risk factors for ACL injury. Clinical Relevance: Genetic profiling to identify athletes at high risk for ACL rupture is not yet feasible.


2019 ◽  
Vol 7 (1) ◽  
pp. 232596711881983 ◽  
Author(s):  
Zoë A. Englander ◽  
Hattie C. Cutcliffe ◽  
Gangadhar M. Utturkar ◽  
William E. Garrett ◽  
Charles E. Spritzer ◽  
...  

Background: Knee positions involved in noncontact anterior cruciate ligament (ACL) injury have been studied via analysis of injury videos. Positions of high ACL strain have been identified in vivo. These methods have supported different hypotheses regarding the role of knee abduction in ACL injury. Purpose/Hypothesis: The purpose of this study was to compare knee abduction angles measured by 2 methods: using a 3-dimensional (3D) coordinate system based on anatomic features of the bones versus simulated 2-dimensional (2D) videographic analysis. We hypothesized that knee abduction angles measured in a 2D videographic analysis would differ from those measured from 3D bone anatomic features and that videographic knee abduction angles would depend on flexion angle and on the position of the camera relative to the patient. Study Design: Descriptive laboratory study. Methods: Models of the femur and tibia were created from magnetic resonance images of 8 healthy male participants. The models were positioned to match biplanar fluoroscopic images obtained as participants posed in lunges of varying flexion angles (FLAs). Knee abduction angle was calculated from the positioned models in 2 ways: (1) varus-valgus angle (VVA), defined as the angle between the long axis of the tibia and the femoral transepicondylar axis by use of a 3D anatomic coordinate system; and (2) coronal plane angle (CPA), defined as the angle between the long axis of the tibia and the long axis of the femur projected onto the tibial coronal plane to simulate a 2D videographic analysis. We then simulated how changing the position of the camera relative to the participant would affect knee abduction angles. Results: During flexion, when CPA was calculated from a purely anterior or posterior view of the joint—an ideal scenario for measuring knee abduction from 2D videographic analysis—CPA was significantly different from VVA ( P < .0001). CPA also varied substantially with the position of the camera relative to the participant. Conclusion: How closely CPA (derived from 2D videographic analysis) relates to VVA (derived from a 3D anatomic coordinate system) depends on FLA and camera orientation. Clinical Relevance: This study provides a novel comparison of knee abduction angles measured from 2D videographic analysis and those measured within a 3D anatomic coordinate system. Consideration of these findings is important when interpreting 2D videographic data regarding knee abduction angle in ACL injury.


2020 ◽  
Vol 54 (9) ◽  
pp. 520-527 ◽  
Author(s):  
Guri Ranum Ekås ◽  
Clare L Ardern ◽  
Hege Grindem ◽  
Lars Engebretsen

ObjectiveTo investigate the risk of new meniscal tears after treatment for anterior cruciate ligament (ACL) injury, in children and adults with and without ACL reconstruction.DesignPrognosis systematic review (PROSPERO registration number CRD42016036788).MethodsWe searched Embase, Ovid Medline, Cochrane, CINAHL, SPORTDiscus, PEDro and Google Scholar from inception to 3rd May 2018. Eligible articles included patients with ACL injury (diagnosis confirmed by MRI and/or diagnostic arthroscopy), reported the number of meniscal tears at the time of ACL injury diagnosis/start of treatment and reported the number of new meniscal tears that subsequently occurred. Articles with fewer than 20 patients at follow-up, and articles limited to ACL revision surgery or multi-ligament knee injuries were excluded. Two independent reviewers screened articles, assessed eligibility, assessed risk of bias and extracted data. We judged the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group methodology.ResultsOf 75 studies included in the systematic review, 54 studies with 9624 patients and 501 new meniscal tears were appropriate for quantitative analysis. Heterogeneity precluded data pooling. The risk of new meniscal tears was 0%–21% when follow-up was <2 years, 0%–29% when follow-up was 2 to 5 years, 5%–52% when follow-up was 5 to 10 years and 4%–31% when follow-up was longer than 10 years. The proportion of studies with high risk of selection, misclassification and detection bias was 84%, 69% and 68%, respectively. Certainty of evidence was very low.ConclusionNew meniscal tears occurred in 0%–52% of patients between 4 months and 20 years (mean 4.9±4.4 years) following treatment for ACL injury. The certainty of evidence was too low to guide surgical treatment decisions. This review cannot conclude that the incidence of new meniscal tears is lower if ACL injury is treated with surgery compared with treatment with rehabilitation only.


2015 ◽  
Vol 50 (10) ◽  
pp. 1005-1010 ◽  
Author(s):  
Dustin R. Grooms ◽  
Stephen J. Page ◽  
James A. Onate

Background Anterior cruciate ligament (ACL) injury has multifactorial causes encompassing mechanical, hormonal, exposure, and anatomical factors. Alterations in the central nervous system also play a role, but their influence after injury, recovery, and recurrent injury remain unknown. Modern neuroimaging techniques can be used to elucidate the underlying functional and structural alterations of the brain that predicate the neuromuscular control adaptations associated with ACL injury. This knowledge will further our understanding of the neural adaptations after ACL injury and rehabilitation and in relation to injury risk. In this paper, we describe the measurement of brain activation during knee extension-flexion after ACL injury and reconstruction and 26 days before a contralateral ACL injury. Methods Brain functional magnetic resonance imaging data for an ACL-injured participant and a matched control participant were collected and contrasted. Results Relative to the matched control participant, the ACL-injured participant exhibited increased activation of motor-planning, sensory-processing, and visual-motor control areas. A similar activation pattern was present for the contralateral knee that sustained a subsequent injury. Conclusions Bilateral neuroplasticity after ACL injury may contribute to the risk of second injury, or aspects of neurophysiology may be predisposing factors to primary injury. Clinical Implications Sensory-visual-motor function and motor-learning adaptations may provide targets for rehabilitation.


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