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Differences in the expression profiles of lncRNAs and mRNAs in partially injured anterior cruciate ligament and medial collateral ligament of rabbits.

ABSTRACT: Long noncoding RNAs (lncRNAs), as a novel regulatory factor, are considered to play a vital role in various biological processes and diseases. However, the overall expression profile and biological functions of lncRNAs in the partially injured anterior cruciate ligament (ACL) and medial collateral ligament (MCL) have not been clearly explored. Partially injured models of ACL and MCL were established in 3-month-old healthy male New Zealand white rabbits. Expression of lncRNAs and mRNAs in the ligament tissue was detected by high-throughput sequencing technology, and biological functions of differentially expressed RNAs were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Validation of several differentially expressed RNAs was performed using quantitative real-time PCR (qRT-PCR). Protein-protein interaction (PPI) analysis and competitive endogenous RNA (ceRNA) prediction were used to identify interactions among hub genes and the interaction among lncRNAs, miRNAs, and mRNAs. The results showed that compared with the normal group, there were 267 mRNAs and 329 lncRNAs differentially expressed in ACL and 726 mRNAs and 609 lncRNAs in MCL in the injured group. Compared with MCL, 420 mRNAs and 470 lncRNAs were differentially expressed in ACL in the normal group; 162 mRNAs and 205 lncRNAs were differentially expressed in ACL in the injured group. Several important lncRNAs and genes were identified, namely, COL7A1, LIF, FGFR2, EPHA2, CSF1, MMP2, MMP9, SOX5, LOX, MSTRG.1737.1, MSTRG.26038.25, MSTRG.20209.5, MSTRG.22764.1, and MSTRG.18113.1, which are closely related to inflammatory response, tissue damage repair, cell proliferation, differentiation, migration, and apoptosis. Further study of the functions of these genes may help to better understand the specific molecular mechanisms underlying the occurrence of endogenous repair disorders in ACL, which may provide new ideas for further exploration of effective means to promote endogenous repair of ACL injury.

SUBMITTER: Gu H

PROVIDER: S-EPMC8760859 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Both the anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) bear load during athletic tasks of landing, cutting, pivoting, and twisting. As dynamic knee valgus is a purported mechanism for ACL injury, the MCL should bear significant strain load with valgus force. HYPOTHESIS:The intact MCL will demonstrate a significant increase in strain upon failure of the ACL at 25° of knee flexion. STUDY DESIGN:Controlled laboratory study. METHODS:In vivo kinetics/kinematics of 44 healthy athletic participants were measured to determine stratification of injury risk (ie, low, medium, and high) in 3 degrees of knee forces/moments (knee abduction moment, anterior tibial shear, and internal tibial rotation). These stratified kinetic values were input into a cadaveric impact simulator to assess ligamentous strain during a simulated landing task. Uniaxial and multiaxial load cells and differential variable reluctance transducer strain sensors were utilized to collect mechanical data for analysis. Conditions of external loads applied to the cadaveric limbs were varied and randomized. RESULTS:ACL strain increased with increased dynamic knee abduction moment (?2[5] = 14.123, P = .0148). The most extreme dynamic knee abduction moment condition demonstrated significantly higher ACL strain compared with lower loaded trials (P? .0203). Similarly, MCL strain increased with dynamic knee abduction moment (?2[5] = 36.578, P < .0001). Matched-pairs analysis compared ACL strain with MCL strain (maximum ACL strain - maximum MCL strain) and demonstrated high strain for the ACL versus the MCL (S177 = 6223.5, P < .0001). CONCLUSION:Although significant, MCL strain had minimal increase with increased dynamic knee abduction moment, and the event of ACL failure did not significantly increase MCL strain when compared with high dynamic knee abduction moment conditions in the cadaveric model. The ACL bears more strain than the MCL at increasing amounts of dynamic knee abduction moment at 25° of knee flexion, which may explain the limited concomitant MCL injury rate that can occur during a dynamic valgus collapse of the knee. CLINICAL RELEVANCE:These characteristics of ACL and MCL strain are important to understand the mechanisms that drive these injuries at the knee and will improve rehabilitation and injury prevention techniques.

Project description:PurposeTo evaluate differences in repair and nonoperatively managed grade III medial collateral ligament (MCL) injuries during anterior cruciate ligament (ACL) reconstruction.MethodsPatients enrolled in a multicenter prospective longitudinal group who underwent unilateral primary ACL reconstruction between 2002 and 2008 were evaluated. Patients with concomitant grade III MCL injuries treated either operatively or nonoperatively were identified. Concurrent injuries, subsequent surgeries, surgical chronicity, and MCL tear location were analyzed. Patient-reported outcomes were measured at time of ACL reconstruction and 2-year follow-up.ResultsInitially, 3,028 patients were identified to have undergone primary ACL reconstruction during the time frame; 2,586 patients completed 2-year follow-up (85%). Grade III MCL tears were documented in 1.1% (27 of 2,586): 16 operatively managed patients and 11 nonoperatively treated MCLs during ACL reconstruction. The baseline Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee scores were lower in patients who underwent operative MCL treatment. Reoperation rates for arthrofibrosis were 19% after repair and 9% after conservative management (P = .48). At 2 years, both groups significantly improved; however, the nonoperative MCL group maintained superior patient-reported outcomes in terms of minimal clinically important differences, but these differences did not reach statistical significance (KOOS sports/recreation [88.2 vs 74.4, P = .10], KOOS knee-related quality of life [81.3 vs 68.4, P = .13], and International Knee Documentation Committee [87.6 vs 76.0, P = .14]). Tibial-sided MCL injuries were associated with clinically inferior baseline scores compared with femoral-sided MCL (KOOS knee-related quality of life, 34.4 vs 18.5, P = .09), but these differences resolved by 2 years. Surgical chronicity did not influence 2-year outcome.ConclusionsBoth operative and nonoperative management of MCL tears in our patient group demonstrated clinical improvements between study enrollment and 2-year follow-up. MCL surgery during ACL reconstruction was assigned to patients with worse symptoms at enrollment and was associated with worse outcomes at 2 years. A subset of patients with severe combined ACL and medial knee injuries may benefit from operative management; however, that population has yet to be defined.Level of evidenceLevel III, retrospective cohort.

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Differences in the expression profiles of lncRNAs and mRNAs in partially injured anterior cruciate ligament and medial collateral ligament of rabbits.

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