Cartilage Composition Research Articles

Associations between less knee kinematic variability and worse patient-reported outcomes following anterior cruciate ligament reconstruction

ABSTRACT Individuals with anterior cruciate ligament reconstruction (ACLR) exhibit less knee kinematic variability while walking than uninjured controls, associated with deleterious changes in cartilage composition linked to an increased risk for early knee osteoarthritis (KOA). It is unknown whether less knee kinematic variability is also associated with worse knee-related patient-reported outcomes (PROs) consistent with KOA development. This study examined associations between kinematic variability during gait and PROs in individuals post-ACLR. Gait kinematics and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were collected from 45 participants 6-months post-ACLR (67% Females; 21.45 ± 4.56 years). Overground gait biomechanics using 3D motion capture were collected, and knee kinematics were extracted for post-processing. Sample entropy (SampEn) was used to calculate knee kinematic variability. Pearson’s product-moment correlations were conducted to determine the associations between SampEn and KOOS sub-scores. Additionally, independent samples t-tests were performed to evaluate potential differences in SampEn outcomes between individuals with and without clinically relevant symptoms (defined in the introduction). Less sagittal plane kinematic variability is associated with greater pain (r = 0.37, p = 0.01) and symptoms (r = 0.32, p = 0.03). Symptomatic participants demonstrated less sagittal plane knee kinematic variability compared to asymptomatic participants (p = 0.01). The findings suggest less variable gait patterns 6-months post-ACLR may be linked to KOA-related symptoms.

Standardized maps – an emerging approach to leverage quantitative information in knee imaging

ObjectiveProperty maps, which capture spatial variations across the entire joint, are emerging as a powerful means for extracting and analyzing quantitative information from knee 3D imaging datasets, particularly from CT and MRI data. This perspective paper aims to discuss the processing pipelines used so far, as well as the results they have enabled with respect to osteoarthritis. DesignThe key methodological steps for obtaining property maps, including segmentation, property calculation, and standardization are presented and analysis methods are discussed. Representative studies are also examined to illustrate the state-of-the-art in this field. ResultsThree main processing pipelines have been used, with the segmentation, property calculation, and standardization steps occurring in different orders. Many methods have been successfully considered for ordering these steps, without any looking generally preferable to the others. Thanks to recent advances in segmentation and standardization techniques, routine processing of property maps appears conceivable in the near future. Maps have been analyzed for multiple purposes, including group comparisons, pattern recognition, and cross-property modelling. Mostly maps of cartilage thickness and composition, as well as maps of bone shape and mineral density have been reported. They revealed distinct patterns associated with osteoarthritis severity, achieved high diagnostic accuracy, and identified relationships among tissue properties. ConclusionsProperty maps represent a promising approach for leveraging the extensive information in imaging data. They are particularly interesting for standardizing complex spatial variations in tissue properties, enabling global analysis and modelling. Once challenging to obtain and interpret, current mapping methods are being improved to the point that property maps may well be in routine use in the near future.

Effect of older age and/or ACL injury on the dose–response relationship between ambulatory load magnitude and immediate load-induced change in serum cartilage oligomeric matrix protein

PurposeThis study aimed to assess the influence of older vs. younger age and previous anterior cruciate ligament (ACL) injury on resting serum cartilage oligomeric matrix protein (sCOMP[tpre]) concentration, on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress (∆_sCOMP[tpost]), and on the dose–response relationship between ambulatory load magnitude and ∆_sCOMP(tpost). MethodsA total of 85 participants were recruited in 4 groups (20–30 years: 24 healthy, 23 ACL-injured; 40–60 years: 23 healthy, 15 ACL-injured). Blood samples were collected immediately before and after a walking stress at 80%, 100%, or 120% bodyweight (BW) on 3 test days and analyzed for sCOMP concentration. Linear models were used to estimate the effect of age, knee status (unilateral ACL injury, 2–10 years prior), and sex on sCOMP(tpre), ∆_sCOMP(tpost)), and the dose–response between ambulatory load magnitude and ∆_sCOMP(tpost). ResultsWe found that sCOMP(tpre) was 21% higher in older than younger participants (p < 0.001) but did not differ between ACL-injured and healthy participants (p = 0.632). Also, ∆_sCOMP(tpost) was 19% lower in older than younger participants (p = 0.030) and increased with body mass index (p < 0.001), sCOMP(tpre) (p = 0.008), and with 120%BW (p < 0.001), independent of age, ACL injury, or sex. ConclusionAge but not prior ACL injury influences resting sCOMP and load-induced sCOMP. The dose–response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age, ACL injury, or sex. A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.

Evaluation of an automated laminar cartilage T2 relaxation time analysis method in an early osteoarthritis model.

A fully automated laminar cartilage composition (MRI-based T2) analysis method was technically and clinically validated by comparing radiographically normal knees with (CL-JSN) and without contra-lateral joint space narrowing or other signs of radiographic osteoarthritis (OA, CL-noROA). 2D U-Nets were trained from manually segmented femorotibial cartilages (n = 72) from all 7 echoes (AllE), or from the 1st echo only (1stE) of multi-echo-spin-echo (MESE) MRIs acquired by the Osteoarthritis Initiative (OAI). Because of its greater accuracy, only the AllE U-Net was then applied to knees from the OAI healthy reference cohort (n = 10), CL-JSN (n = 39), and (1:1) matched CL-noROA knees (n = 39) that all had manual expert segmentation, and to 982 non-matched CL-noROA knees without expert segmentation. The agreement (Dice similarity coefficient) between automated vs. manual expert cartilage segmentation was between 0.82 ± 0.05/0.79 ± 0.06 (AllE/1stE) and 0.88 ± 0.03/0.88 ± 0.03 (AllE/1stE) across femorotibial cartilage plates. The deviation between automated vs. manually derived laminar T2 reached up to - 2.2 ± 2.6ms/ + 4.1 ± 10.2ms (AllE/1stE). The AllE U-Net showed a similar sensitivity to cross-sectional laminar T2 differences between CL-JSN and CL-noROA knees in the matched (Cohen's D ≤ 0.54) and the non-matched (D ≤ 0.54) comparison as the matched manual analyses (D ≤ 0.48). Longitudinally, the AllE U-Net also showed a similar sensitivity to CL-JSN vs. CS-noROA differences in the matched (D ≤ 0.51) and the non-matched (D ≤ 0.43) comparison as matched manual analyses (D ≤ 0.41). The fully automated T2 analysis showed a high agreement, acceptable accuracy, and similar sensitivity to cross-sectional and longitudinal laminar T2 differences in an early OA model, compared with manual expert analysis. Clinicaltrials.gov identification: NCT00080171.

Revealing chemistry-structure-function relationships in shark vertebrae across length scales

Shark cartilage presents a complex material composed of collagen, proteoglycans, and bioapatite. In the present study, we explored the link between microstructure, chemical composition, and biomechanical function of shark vertebral cartilage using Polarized Light Microscopy (PLM), Atomic Force Microscopy (AFM), Confocal Raman Microspectroscopy, and Nanoindentation. Our investigation focused on vertebrae from Blacktip and Shortfin Mako sharks. As typical representatives of the orders Carcharhiniformes and Lamniformes, these species differ in preferred habitat, ecological role, and swimming style. We observed structural variations in mineral organization and collagen fiber arrangement using PLM and AFM. In both sharks, the highly calcified corpus calcarea shows a ridged morphology, while a chain-like network is present in the less mineralized intermedialia. Raman spectromicroscopy demonstrates a relative increase of glucosaminocycans (GAGs) with respect to collagen and a decrease in mineral-rich zones, underlining the role of GAGs in modulating bioapatite mineralization. Region-specific testing confirmed that intravertebral variations in mineral content and arrangement result in distinct nanomechanical properties. Local Young's moduli from mineralized regions exceeded bulk values by a factor of 10. Overall, this work provides profound insights into a flexible yet strong biocomposite, which is crucial for the extraordinary speed of cartilaginous fish in the worlds’ oceans. Statement of significanceShark cartilage is a morphologically complex material composed of collagen, sulfated proteoglycans, and calcium phosphate minerals. This study explores the link between microstructure, chemical composition, and biological mechanical function of shark vertebral cartilage at the micro- and nanometer scale in typical Carcharhiniform and Lamniform shark species, which represent different vertebral mineralization morphologies, swimming styles and speeds. By studying the intricacies of shark vertebrae, we hope to lay the foundation for biomimetic composite materials that harness lamellar reinforcement and tailored stiffness gradients, capable of dynamic and localized adjustments during movement.

The relationships between patellofemoral bone remodeling, cartilage composition, and vertical loading rate: PET/MRI in isolated patellofemoral osteoarthritis

ObjectiveLoading is invariably an important factor of consideration for understanding the causality flow and parallel existence of articular cartilage and subchondral bone changes. The goal of this study was to investigate the patterns of subregional 18NaF-SUV vs. T1p-T2 associations and vertical ground reaction force loading rates; in isolated patellofemoral-joint-osteoarthritis (PFJ-OA) patients. MethodThirty-five isolated PFJ-OA patients, with no tibiofemoral involvement, underwent simultaneous scans in a 3.0T whole-body hybrid PET-MRI scanner. MRI WORMS assessments were performed to identify/confirm isolated PFJ-OA knees from bilateral scans. T1p-T2 relaxation and SUV values were automatically computed for both trochlear and patellar cartilage and subchondral bone subregions (deep, superficial, lateral, and medial). Maximum vertical impact loading rates (Loading-RateNorm) were calculated from walking trials. Relationships were explored between SUV uptake, T1p-T2 values, and Loading-RateNorm via linear mixed-effects modeling. ResultsSignificant and complex association patterns were noted between medial and lateral bone 18NaF-SUV uptakes vs. medial and lateral cartilage sub-regional T1p and T2. SUVMean and SUVMax were positively associated with deep cartilage subregional T1pand T2 values; and negatively associated with superficial cartilage subregional T1p-T2 values in both medial and lateral regions. Both medial and lateral bone 18NaF-SUVMean and SUVMax uptakes remained positively associated with the individual gait characteristics, i.e., peak vertical impact loading rates (Loading-RateNorm). ConclusionEvidence of simultaneous, complementary, cross-sectional associations between T1p-T2 values and peak vertical loading rates with 18NaF-SUV, have been rare in the isolated PFJ-OA cohort. The clinical implications of such novel associations remain of utmost importance from a gait retraining perspective.

In the Acute Phase of Anterior Cruciate Ligament Rupture: Quantitative Assessment of Matrix Changes and Correlation between Different States of Meniscus and Adjacent Cartilage.

Cartilage and meniscus are important structures that maintain the health of the knee joint. Early detection of changes in the internal components of cartilage and meniscus before morphological changes occur is essential to prevent and delay the development of osteoarthritis (OA). This study was designed to determine the changes in the matrix composition of morphologically intact cartilage and meniscus during the acute phase of an anterior cruciate ligament (ACL) rupture, as well as the effect of different states of meniscus (intact or tear) on adjacent cartilage during the acute phase. This cross-sectional study compared and analyzed 50 patients in the acute phase of ACL rupture who underwent surgical treatment and 66 age-, weight- and height-matched healthy volunteers from May 2022 to May 2023 at our institution. Mean T2 relaxation times and effect sizes in different regions of tibiofemoral articular cartilage and meniscus were compared between the two groups using the Mann-Whitney nonparametric t-test, and correlations between different meniscal states and adjacent cartilage were analyzed. Both in the lateral and medial compartments of the knee, T2 relaxation times were significantly higher in all subregions of cartilage and meniscus in the ACL rupture group (p < 0.05), and the site of injury was predominantly centered in the medial compartment (femur, p = 0.000; tibia, p = 0.000; anterior horn, p = 0.000). In the respective compartments, the posterior horn of the lateral meniscus showed a significant positive correlation with the mid-cartilage of the femoral and tibial (r = 0.566, p = 0.035; r = 0.611, p = 0.02); and the posterior horn of the medial meniscus showed a significant positive correlation with the posterior tibial cartilage (r = 0.668, p = 0.018). During the acute phase of ACL rupture, the internal composition of the cartilage and meniscus undergoes significant changes, even if the morphology is intact. More importantly, the state of the meniscus significantly affects the internal composition of the adjacent cartilage. This is an early warning sign of OA, which should be closely monitored and carefully managed in clinical practice.

Association of Serum Biochemical Biomarker Profiles of Joint Tissue Inflammation and Cartilage Metabolism With Posttraumatic Osteoarthritis-Related Symptoms at 12 Months After ACLR

Background: Anterior cruciate ligament injury and anterior cruciate ligament reconstruction (ACLR) are risk factors for symptomatic posttraumatic osteoarthritis (PTOA). After ACLR, individuals demonstrate altered joint tissue metabolism indicative of increased inflammation and cartilage breakdown. Serum biomarker changes have been associated with tibiofemoral cartilage composition indicative of worse knee joint health but not with PTOA-related symptoms. Purpose/Hypothesis: The purpose of this study was to determine associations between changes in serum biomarker profiles from the preoperative sample collection to 6 months after ACLR and clinically relevant knee PTOA symptoms at 12 months after ACLR. It was hypothesized that increases in biomarkers of inflammation, cartilage metabolism, and cartilage degradation would be associated with clinically relevant PTOA symptoms after ACLR. Study Design: Case-control study; Level of evidence, 3. Methods: Individuals undergoing primary ACLR were included (N = 30). Serum samples collected preoperatively and 6 months after ACLR were processed to measure markers indicative of changes in inflammation (ie, monocyte chemoattract protein 1 [MCP-1]) and cartilage breakdown (ie, cartilage oligomeric matrix protein [COMP], matrix metalloproteinase 3, ratio of type II collagen breakdown to type II collagen synthesis). Knee injury and Osteoarthritis Outcome Score surveys were completed at 12 months after ACLR and used to identify participants with and without clinically relevant PTOA-related symptoms. K-means cluster analyses were used to determine serum biomarker profiles. One-way analyses of variance and logistic regressions were used to assess differences in Knee injury and Osteoarthritis Outcome Score subscale scores and clinically relevant PTOA-related symptoms between biomarker profiles. Results: Two profiles were identified and characterized based on decreases (profile 1: 67% female; age, 21.4 ± 5.1 years; body mass index, 24.4 ± 2.4) and increases (profile 2: 33% female; age, 21.3 ± 3.2 years; body mass index, 23.4 ± 2.6) in sMCP-1 and sCOMP preoperatively to 6 months after ACLR. Participants with profile 2 did not demonstrate differences in knee pain, symptoms, activities of daily living, sports function, or quality of life at 12 months after ACLR compared to those with profile 1 (P = .56-.81; η2 = 0.002-0.012). No statistically significant associations were noted between biomarker profiles and clinically relevant PTOA-related symptoms (odds ratio, 1.30; 95% CI, 0.23-6.33). Conclusion: Serum biomarker changes in MCP-1 and sCOMP within the first 6 months after ACLR were not associated with clinically relevant PTOA-related symptoms.

Posttraumatic osteoarthritis after athletic knee injury: A narrative review of diagnostic imaging strategies.

Intraarticular knee injuries and subsequent posttraumatic arthritis (PTOA) are common in athletes. Unfortunately, PTOA may significantly affect performance and overall function, but this condition remains difficult to characterize. In this review, we provide an overview of imaging modalities used to evaluate PTOA among athletes and physically active individuals following knee injury, with the goal to discuss the strengths and limitations of their application in this population. A literature search was performed to identify clinical studies focusing of knee injuries in athletes and athletic persons, specifically using imaging for diagnosis or monitoring disease progression. A total of 81 articles were identified, and 23 were included for review. Studies on plain radiographs (n = 8) and magnetic resonance imaging (MRI) assessed arthritic burden (n = 13), with MRI able to depict the earliest cartilage changes. Few studies (n = 2) leveraged ultrasound. Challenges persist, particularly regarding standardization and reliability across different radiographic grading systems. Additionally, further research is needed to establish the clinical significance of techniques to assess cartilage composition on MRI, including ultrashort echo-time enhanced T2*, T1rho and T2 imaging. Addressing these challenges through standardized protocols and intensified research efforts will enhance the diagnostic utility of imaging modalities in musculoskeletal medicine and enable high-quality prospective studies.

(Chemical) Roles of HOCl in Rheumatic Diseases.

Chronic rheumatic diseases such as rheumatoid arthritis (RA) are characterized by a dysregulated immune response and persistent inflammation. The large number of neutrophilic granulocytes in the synovial fluid (SF) from RA patients leads to elevated enzyme activities, for example, from myeloperoxidase (MPO) and elastase. Hypochlorous acid (HOCl), as the most important MPO-derived product, is a strong reactive oxygen species (ROS) and known to be involved in the processes of cartilage destruction (particularly regarding the glycosaminoglycans). This review will discuss open questions about the contribution of HOCl in RA in order to improve the understanding of oxidative tissue damaging. First, the (chemical) composition of articular cartilage and SF and the mechanisms of cartilage degradation will be discussed. Afterwards, the products released by neutrophils during inflammation will be summarized and their effects towards the individual, most abundant cartilage compounds (collagen, proteoglycans) and selected cellular components (lipids, DNA) discussed. New developments about neutrophil extracellular traps (NETs) and the use of antioxidants as drugs will be outlined, too. Finally, we will try to estimate the effects induced by these different agents and their contributions in RA.

Clinical validation of fully automated laminar knee cartilage transverse relaxation time (T2) analysis in anterior cruciate ligament (ACL)-injured knees- on behalf of the osteoarthritis (OA)-Bio consortium.

Magnetic resonance imaging (MRI) cartilage transverse relaxation time (T2) reflects cartilage composition, mechanical properties, and early osteoarthritis (OA). T2 analysis requires cartilage segmentation. In this study, we clinically validate fully automated T2 analysis at 1.5 Tesla (T) in anterior cruciate ligament (ACL)-injured and healthy knees. We studied 71 participants: 20 ACL-injured patients with, and 22 without dynamic knee instability, 13 with surgical reconstruction, and 16 healthy controls. Sagittal multi-echo-spin-echo (MESE) MRIs were acquired at baseline and 1-year follow-up. Femorotibial cartilage was segmented manually; a convolutional neural network (CNN) algorithm was trained on MRI data from the same scanner. Dice similarity coefficients (DSCs) of automated versus manual segmentation in the 71 participants were 0.83 (femora) and 0.89 (tibiae). Deep femorotibial T2 was similar between automated (45.7±2.6 ms) and manual (45.7±2.7 ms) segmentation (P=0.828), whereas superficial layer T2 was slightly overestimated by automated analysis (53.2±2.2 vs. 52.1±2.1 ms for manual; P<0.001). T2 correlations were r=0.91-0.99 for deep and r=0.86-0.97 for superficial layers across regions. The only statistically significant T2 increase over 1 year was observed in the deep layer of the lateral femur [standardized response mean (SRM) =0.58 for automated vs. 0.52 for manual analysis; P<0.001]. There was no relevant difference in baseline/longitudinal T2 values/changes between the ACL-injured groups and healthy participants, with either segmentation method. This clinical validation study suggests that automated cartilage T2 analysis from MESE at 1.5T is technically feasible and accurate. More efficient 3D sequences and longer observation intervals may be required to detect the impact of ACL injury induced joint instability on cartilage composition (T2).

Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy.

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements thatcontain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

Relationships Between Running Biomechanics and Femoral Articular Cartilage Thickness and Composition in Anterior Cruciate Ligament Reconstruction Patients.

Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. Twenty patients with ACLR (time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self-selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = -0.99 and p = 0.004) during running. Our findings suggest that those who are between 6 and 24 months post-ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF.

Treatment of Knee Chondral Defects in Athletes.

Cartilage lesions of the knee are a challenging problem, especially for active individuals and athletes who desire a return to high-load activities. They occur both through chronic repetitive loading of the knee joint or through acute traumatic injury and represent a major cause of pain and time lost from sport. They can arise as isolated lesions or in association with concomitant knee pathology. Management of these defects ultimately requires a sound understanding of their pathophysiologic underpinnings to help guide treatment. Team physicians should maintain a high index of suspicion for underlying cartilage lesions in any patient presenting with a knee effusion, whether painful or not. A thorough workup should include a complete history and physical examination. MRI is the most sensitive and specific imaging modality to assess these lesions and can provide intricate detail not only of the structure and composition of cartilage, but also of the surrounding physiological environment in the joint. Treatment of these lesions consists of both conservative or supportive measures, as well as surgical interventions designed to restore or regenerate healthy cartilage. Because of the poor inherent capacity for healing associated with hyaline cartilage, the vast majority of symptomatic lesions will ultimately require surgery. Surgical treatment options range from simple arthroscopic debridement to large osteochondral reconstructions. Operative decision-making is based on numerous patient- and defect-related factors and requires open lines of communication between the athlete, the surgeon, and the rest of the treatment team. Ultimately, a positive outcome is based on the creation of a durable, resistant repair that allows the athlete to return to pain-free sporting activities.

Anterior cruciate ligament injury and age affect knee cartilage T2 but not thickness

ObjectiveTo investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls. DesignQuantitative double-echo steady-state (qDESS) 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20–30 years: healthy, HEA20–30, n=24; ACL-injured, ACL20–30, n=23; 40–60 years: healthy, HEA40–60, n=24; ACL-injured, ACL40–60, n=14 (ACL injury 2–10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side difference in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics. ResultsCartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL20–30 than in HEA20–30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls. ConclusionIn the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in the diagnosing and monitoring early articular cartilage changes.

Osteophyte Cartilage as a Potential Source for Minced Cartilage Implantation: A Novel Approach for Articular Cartilage Repair in Osteoarthritis.

Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA.

Compositional MR imaging of cartilage and joint mechanics

MRI-based compositional measurements of cartilage have been developed to characterize the biochemical composition of articular cartilage and the menisci, allowing the assessment of cartilage quality before cartilage loss has occurred and changes are still potentially reversible. They have also been used to investigate the complex relationship between biomechanics and cartilage health. This review focuses on cartilage T1rho and T2 cartilage compositional measurements as these techniques have been most frequently used in studies involving joint biomechanics. Recent clinical and in vitro studies are covered, including those investigating the relationship of cartilage composition with physical activity, gait, muscle strength, and biomechanical loading of specimens. These studies clearly illustrate the impact of physical activity on cartilage, how gait alterations after anterior cruciate ligament reconstruction may lead to early degenerative disease, and the complex interplay between muscle strength, gait, and cartilage composition. In vitro work also demonstrates how indentation stiffness correlates with cartilage composition. The review further consolidates the important role of cartilage compositional imaging in understanding the biomechanics and pathophysiology of degenerative joint disease.

Reproducibility of Quantitative Double-Echo Steady-State T2 Mapping of Knee Cartilage.

Cartilage T2 can detect joints at risk of developing osteoarthritis. The quantitative double-echo steady state (qDESS) sequence is attractive for knee cartilage T2 mapping because of its acquisition time of under 5 minutes. Understanding the reproducibility errors associated with qDESS T2 is essential to profiling the technical performance of this biomarker. To examine the combined acquisition and segmentation reproducibility of knee cartilage qDESS T2 using two different regional analysis schemes: 1) manual segmentation of subregions loaded during common activities and 2) automatic subregional segmentation. Prospective. 11 uninjured participants (age: 28 ± 3 years; 8 (73%) female). 3-T, qDESS. Test-retest T2 maps were acquired twice on the same day and with a 1-week interval between scans. For each acquisition, average cartilage T2 was calculated in four manually segmented regions encompassing tibiofemoral contact areas during common activities and 12 automatically segmented regions from the deep-learning open-source framework for musculoskeletal MRI analysis (DOSMA) encompassing medial and lateral anterior, central, and posterior tibiofemoral regions. Test-retest T2 values from matching regions were used to evaluate reproducibility. Coefficients of variation (%CV), root-mean-square-average-CV (%RMSA-CV), and intraclass correlation coefficients (ICCs) assessed test-retest T2 reproducibility. The median of test-retest standard deviations was used for T2 precision. Bland-Altman (BA) analyses examined test-retest biases. The smallest detectable difference (SDD) was defined as the BA limit of agreement of largest magnitude. Significance was accepted for P < 0.05. All cartilage regions across both segmentation schemes demonstrated intraday and interday qDESS T2 CVs and RMSA-CVs of ≤5%. T2 ICC values >0.75 were observed in the majority of regions but were more variable in interday tibial comparisons. Test-retest T2 precision was <1.3 msec. The T2 SDD was 3.8 msec. Excellent CV and RMSA-CV reproducibility may suggest that qDESS T2 increases or decreases >5% (3.8 msec) could represent changes to cartilage composition. Stage 2.

The value of adding T2 mapping sequence to the routine MRI protocol in the evaluation of cartilage lesions of the ankle joint

BackgroundAnkle joint cartilage injury is frequently associated with degenerative changes, even in the absence of symptoms. Earlier treatment of cartilage damage with joint preservation is clearly more successful. The main limitation of morphologic cartilage magnetic resonance imaging sequences is that they are not very sensitivity in the detection of early cartilage degeneration. Recent advances in biochemical magnetic resonance imaging have yielded sequences that are sensitive to molecular changes in the composition of cartilage matrix. This includes water- and collagen-sensitive T2\\T2* mapping. The aim of this study was to determine the extent of improvement of the diagnostic performance of routine magnetic resonance imaging protocol in the evaluation of ankle joint articular cartilage lesions following the addition of a T2 mapping sequence.ResultsA total of 45 cases, 30 patients (12 male and 18 female) and 15 controls (10 male and 5 female) who underwent routine ankle magnetic resonance imaging with additional T2 mapping sequence, were included in the study. Out of 30 patients, four patients were misdiagnosed as being normal, while having changes of cartilage composition of early degenerative changes, discovered by T2 mapping sequence. The patients group as well as the-control groups had significantly higher T2-values in the superficial cartilage layer (P < 0.001) compared to the deep layer. When comparing between the medial and the lateral compartments at patients group, the T2-relaxation times were more pronounced in the medial talar cartilage compartment compared to the lateral talar cartilage compartment.ConclusionsMagnetic resonance imaging can observe not only the destruction of the structural integrity but also the change of the components in articular cartilage. In this study, the addition of a T2 mapping of the ankle cartilage sequence to a routine MR ankle protocol improved sensitivity and accuracy in the detection of early cartilage lesions within the ankle joint.

IL-17RA Signaling in Prx1+ Mesenchymal Cells Influences Fracture Healing in Mice.

Fracture healing is a complex series of events that requires a local inflammatory reaction to initiate the reparative process. This inflammatory reaction is important for stimulating the migration and proliferation of mesenchymal progenitor cells from the periosteum and surrounding tissues to form the cartilaginous and bony calluses. The proinflammatory cytokine interleukin (IL)-17 family has gained attention for its potential regenerative effects; however, the requirement of IL-17 signaling within mesenchymal progenitor cells for normal secondary fracture healing remains unknown. The conditional knockout of IL-17 receptor a (Il17ra) in mesenchymal progenitor cells was achieved by crossing Il17raF/F mice with Prx1-cre mice to generate Prx1-cre; Il17raF/F mice. At 3 months of age, mice underwent experimental unilateral mid-diaphyseal femoral fractures and healing was assessed by micro-computed tomography (µCT) and histomorphometric analyses. The effects of IL-17RA signaling on the osteogenic differentiation of fracture-activated periosteal cells was investigated in vitro. Examination of the intact skeleton revealed that the conditional knockout of Il17ra decreased the femoral cortical porosity but did not affect any femoral trabecular microarchitectural indices. After unilateral femoral fractures, Il17ra conditional knockout impacted the cartilage and bone composition of the fracture callus that was most evident early in the healing process (day 7 and 14 post-fracture). Furthermore, the in vitro treatment of fracture-activated periosteal cells with IL-17A inhibited osteogenesis. This study suggests that IL-17RA signaling within Prx1+ mesenchymal progenitor cells can influence the early stages of endochondral ossification during fracture healing.