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Muscle dysfunction following anterior cruciate ligament reconstruction (ACLR) may evolve from alterations in muscle contractility at the myofilament protein level. Using a prospective, within‐subject case–control design, we evaluated cellular‐level contractility, cross‐sectional area (CSA), and myosin heavy chain (MHC) isoform expression on single muscle fibers 3 weeks post ACLR, and evaluated their relationship to whole muscle strength and patient‐oriented outcomes 6 months post operation. Biopsies of the vastus lateralis were performed 3 weeks post ACLR in 11 subjects (5 females, mean age ± SD = 24.7 ± 6.5 years, height = 172.7 ± 8.2 cm, mass = 75.7 ± 12.5 kg) following first‐time ACL rupture and whole muscle strength and self‐reported pain, function, and quality of life assessed 6 months post ACLR. At 3 weeks post ACLR, force production was reduced (p < 0.01) in MHC I (−36%) and IIA (−48%) fibers compared with the non‐injured leg. When force production was expressed relative to CSA to account for fiber atrophy, reductions remained in MHC IIA fibers (−40%; p < 0.001), but MHC I fibers showed only a trend toward being lower (−13%; p = 0.09). Finally, skeletal muscle fiber functional deficits at 3 weeks post ACLR were associated with whole muscle weakness and less favorable patient‐reported outcomes at 6‐month follow‐up. Thus, ACLR promotes early cellular contractile dysfunction that may contribute to decreased whole muscle strength and patient function, and increased patient‐reported symptoms, at 6‐month follow‐up. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament injury and reconstruction (ACLR) affects articular cartilage thickness profiles about the tibial, femoral, and patellar surfaces; however, it's unclear whether the magnitudes of change in cartilage thickness, as well as the locations and areas over which these changes occur, differ between males and females. This is important to consider as differences exist between the sexes with regard to knee biomechanics, patellofemoral pain, and anatomic alignment, which influence risk of an index and repeated injury. Subjects underwent ACLR with a bone‐patella tendon‐bone autograft. At 4‐year follow‐up, they had asymptomatic knees; however, significant ACL injured‐to‐contralateral normal knee differences in articular cartilage thickness values were observed. Both thickening and thinning of cartilage occurred about the tibiofemoral and patellofemoral joints, relative to matched control subjects with normal knees. Further, the location of the areas and magnitudes of thickening and thinning were different between females and males. Thickening (swelling) of articular cartilage is an early finding associated with the onset of posttraumatic osteoarthritis (PTOA). Therefore, the increases in cartilage thickness that were observed in this cohort may represent early signs of the onset of PTOA that occur prior to the patient developing symptoms and radiographic evidence of this disease. The different locations of areas that underwent a change in cartilage thicknesses between males and females suggest that each sex responds differently to knee ligament trauma, reconstruction, rehabilitation, and return to activity, and indicates that sex‐specific analysis should be utilized in studies of PTOA. [ABSTRACT FROM AUTHOR]

Combined injury to the anterior cruciate ligament (ACL) and meniscus is associated with earlier onset and increased rates of post‐traumatic osteoarthritis compared with isolated ACL injury. However, little is known about the initial changes in joint structure associated with these different types of trauma. We hypothesized that trauma to the ACL and lateral meniscus has an immediate effect on morphometry of the articular cartilage and meniscus about the entire tibial plateau that is more pronounced than an ACL tear without meniscus injury. Subjects underwent magnetic resonance imaging scanning soon after injury and prior to surgery. Those that suffered injury to the ACL and lateral meniscus underwent changes in the lateral compartment (increases in the posterior–inferior directed slopes of the articular cartilage surface, and the wedge angle of the posterior horn of the meniscus) and medial compartment (the cartilage‐to‐bone height decreased in the region located under the posterior horn of the meniscus, and the thickness of cartilage increased and decreased in the mid and posterior regions of the plateau, respectively). Subjects that suffered an isolated ACL tear did not undergo the same magnitude of change to these articular structures. A majority of the changes in morphometry occurred in the lateral compartment of the knee; however, change in the medial compartment of the knee with a normal appearing meniscus also occurred. Statement of clinical significance: Knee injuries that involve combined trauma to the ACL and meniscus directly affect both compartments of the knee, even if the meniscus and articular cartilage appears normal upon arthroscopic examination. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:759‐767, 2020 [ABSTRACT FROM AUTHOR]

ABSTRACT Anterior cruciate ligament (ACL) trauma often occurs in combination with injury to the articular cartilage of the knee, this can result in earlier radiographic evidence of post traumatic osteoarthritis (OA) of the knee compared to the contralateral, ACL intact knee; however, the biomechanical and biological mechanisms associated with the onset and progression of this disease are not understood. We sought to gain insight into the mechanisms by determining the relationship between articular cartilage injury associated with ACL trauma and the expression of synovial fluid biomarkers of articular cartilage metabolism, and to evaluate the relationship between these biomarkers and the patient's perspective of the outcomes. Synovial fluid samples were acquired from 39 ACL injured subjects at an average of 10 weeks after injury, and 32 control subjects with normal knees (documented with clinical exam and MRI assessment). Subjects in the ACL-injured group were classified as low-risk for future OA if they displayed an International Cartilage Repair Society (ICRS) Grade 2 articular cartilage lesion or less and high-risk for future OA if they had an ICRS Grade 3A articular cartilage lesion. The patient's perspective of the injury was evaluated with the Knee Injury and Osteoarthritis Outcomes Score (KOOS). There were no significant differences in mean concentrations of the markers of type II collagen metabolism (CPII, C2C, and C1,2C) or the aggrecan breakdown Alanine-Arginine-Glycine-Serine (ARGS) -fragment between control subjects and the subjects in the low- and high-risk groups ( p-value range: 0.80-0.43). Associations between ARGS-aggrecan concentration and KOOS subscales of symptoms and pain were significantly different between the low- and high-risk groups (p = 0.03 and p = 0.01, respectively). Likewise, there was strong evidence in support of an association between the markers of type II collagen metabolism (C1,2C and CPII concentrations) and the KOOS subscale of pain between the low- and high-risk groups ( p = 0.051 and 0.077, correspondingly). In ACL injured subjects with concomitant Grade 3A articular cartilage injuries, concentrations of synovial fluid ARGS-aggrecan were directly associated with improvements in KOOS symptoms and pain. These findings suggest the possible involvement of ARGS-aggrecan in a localized tissue repair response involving an increase in aggrecan turnover following severe knee trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:820-827, 2016. [ABSTRACT FROM AUTHOR]

ABSTRACT Severe knee trauma, such as an ACL disruption, produces aggrecan degradation as evidenced by elevated synovial fluid (SF) N-terminal (393) Alanine-Arginine-Glycine-Serine (ARGS) neoepitope (or ARGS-aggrecan) and is associated with inflammatory activity soon after injury. However, it is not known if this process persists for a substantial time interval following the initial trauma. The purpose of this study was to evaluate relationships between SF ARGS concentrations and an array of cytokines, matrix metalloproteases (MMPs), and tissue inhibitor of metalloproteases (TIMPs) during the initial 6 months following ACL rupture. SF samples from 67 ACL-injured subjects (29 women) were analyzed within 6 months of injury (18-155 days), immediately prior to surgical ACL reconstruction. Relationships between ARGS and individual analyte concentrations, as well as MMP/TIMP ratios were evaluated. Statistically significant relationships were found between ARGS and basic fibroblast growth factor (FGF2) ( p = 0.03) and TIMP-3 ( p = 0.01). Our findings suggest that FGF2, considered to be primarily catabolic in articular cartilage, is not downregulated as ARGS concentration declines over time since injury. In addition, these results support the hypothesis that an upregulation of TIMP-3, the primary aggrecanase inhibitor, is elicited in response to increased aggrecan degradation, which may inhibit further cleavage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1796-1803, 2015. [ABSTRACT FROM AUTHOR]

Tibial plateau subchondral bone geometry has been associated with the risk of sustaining a non-contact ACL injury; however, little is known regarding the influence of the meniscus and articular cartilage interface geometry on risk. We hypothesized that geometries of the tibial plateau articular cartilage surface and meniscus were individually associated with the risk of non-contact ACL injury. In addition, we hypothesized that the associations were independent of the underlying subchondral bone geometry. MRI scans were acquired on 88 subjects that suffered non-contact ACL injuries (27 males, 61 females) and 88 matched control subjects that were selected from the injured subject's teammates and were thus matched on sex, sport, level of play, and exposure to risk of injury. Multivariate analysis of the female data revealed that increased posterior-inferior directed slope of the middle articular cartilage region and decreased height of the posterior horn of the meniscus in the lateral compartment were associated with increased risk of sustaining a first time, non-contact ACL injury, independent of each other and of the slope of the tibial plateau subchondral bone. No measures were independently related to risk of non-contact ACL injury among males. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1487-1494, 2014. [ABSTRACT FROM AUTHOR]

ABSTRACT Measurements of tibial plateau subchondral bone and articular cartilage slope have been associated with the risk of suffering anterior cruciate ligament (ACL) injury. Such single-plane measures of the tibial plateau may not sufficiently characterize its complex, three-dimensional geometry and how it relates to knee injury. Further, the tibial spines have not been studied in association with the risk of suffering a non-contact ACL injury. We questioned whether the geometries of the tibial spines are associated with non-contact ACL injury risk, and if this relationship is different for males and females. Bilateral MRI scans were acquired on 88 ACL-injured subjects and 88 control subjects matched for sex, age and sports team. Medial and lateral tibial spine geometries were characterized with measurements of length, width, height, volume and anteroposterior location. Analyses of females revealed no associations between tibial spine geometry and risk of ACL injury. Analyses of males revealed that an increased medial tibial spine volume was associated with a decreased risk of ACL injury (OR = 0.667 per 100 mm3 increase). Smaller medial spines could provide less resistance to internal rotation and medial translation of the tibia relative to the femur, subsequently increasing ACL strains and risk of ACL injury. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1451-1457, 2014. [ABSTRACT FROM AUTHOR]

Key points Muscle disuse that accompanies ageing and chronic disease may hasten physical disability by impairing skeletal muscle contractility., We compared skeletal muscle contractile function at the various anatomic levels between two groups of older men and women matched for sex, health status and body size, of which one group was habitually active and the other inactive., Muscle disuse reduced force generation, power output and contractile velocity in single muscle fibres, with differential adaptations in some parameters in men and women. Sex-specific cellular phenotypes were explained by differential adaptations in molecular muscle function. Moreover, aspects of the molecular functional phenotype apparent in inactive women could be recapitulated in vitro by chemical modification of protein thiols., Our results identify molecular and cellular contractile dysfunction in skeletal muscle that may contribute to reduced physical function with muscle disuse, with sex-specific differences that may explain a greater disposition towards disability in women., Abstract Physical inactivity that accompanies ageing and disease may hasten disability by reducing skeletal muscle contractility. To characterize skeletal muscle functional adaptations to muscle disuse, we compared contractile performance at the molecular, cellular and whole-muscle levels in healthy active older men and women ( n = 15) and inactive older men and women with advanced-stage, symptomatic knee osteoarthritis (OA) ( n = 16). OA patients showed reduced ( P < 0.01) knee extensor function. At the cellular level, single muscle fibre force production was reduced in OA patients in myosin heavy chain (MHC) I and IIA fibres (both P < 0.05) and differences in IIA fibres persisted after adjustments for fibre cross-sectional area ( P < 0.05). Although no group differences in contractile velocity or power output were found for any fibre type, sex was found to modify the effect of OA, with a reduction in MHC IIA power output and a trend towards reduced shortening velocity in women, but increases in both variables in men ( P < 0.05 and P = 0.07, respectively). At the molecular level, these adaptations in MHC IIA fibre function were explained by sex-specific differences ( P ≤ 0.05) in myosin-actin cross-bridge kinetics. Additionally, cross-bridge kinetics were slowed in MHC I fibres in OA patients ( P < 0.01), attributable entirely to reductions in women with knee OA ( P < 0.05), a phenotype that could be reproduced in vitro by chemical modification of protein thiol residues. Our results identify molecular and cellular functional adaptations in skeletal muscle that may contribute to reduced physical function with knee OA-associated muscle disuse, with sex-specific differences that may explain a greater disposition towards disability in women. [ABSTRACT FROM AUTHOR]

ABSTRACT The purpose of this study was to determine if geometry of the articular surfaces of the tibial plateau is associated with non-contact anterior cruciate ligament (ACL) injury. This was a longitudinal cohort study with a nested case-control analysis. Seventy-eight subjects who suffered a non-contact ACL tear and a corresponding number of controls matched by age, sex, and sport underwent 3 T MRI of both knees. Surface geometry of the tibial articular cartilage was characterized with polynomial equations and comparisons were made between knees on the same person and between ACL-injured and control subjects. There was no difference in surface geometry between the knees of the control subjects. In contrast, there were significant differences in the surface geometry between the injured and normal knees of the ACL-injured subjects, suggesting that the ACL injury changed the cartilage surface profile. Therefore, comparisons were made between the uninjured knees of the ACL-injured subjects and the corresponding knees of their matched controls and this revealed significant differences in the surface geometry for the medial ( p < 0.006) and lateral ( p < 0.001) compartments. ACL-injured subjects tended to demonstrate a posterior-inferior directed orientation of the articular surface relative to the long axis of the tibia, while the control subjects were more likely to show a posterior-superior directed orientation. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:61-68, 2014. [ABSTRACT FROM AUTHOR]