Knee Tissues Research Articles

The Histopathological Examination of the Degeneration of Menisci in Osteoarthritic Knees Using an Adapted Bonar Score: Does Osteoarthritis Equally Influence the Lateral and Medial Menisci?

This study aimed to investigate the degeneration of the meniscal tissue in osteoarthritic knees and to adapt the Bonar score and its modifications to develop a microscopic examination. This study included consecutive patients who underwent total knee arthroplasty for symptomatic end-stage gonarthrosis. During the surgery, the menisci were completely dissected to preserve their original shapes. The samples were prepared using the hematoxylin and eosin (H&E) staining method and the Alcian blue protocol and were examined under light microscopy. The extent of histopathological changes was assessed based on the classical Bonar score assumptions. Additionally, in the second step of the examination, menisci remnants were evaluated using the modified Bonar score developed by Zabrzyński et al. The study involved 44 patients, from whom 83 samples of knee menisci were obtained. Histological examination of the meniscal specimens under a light microscope revealed tissue degeneration in all cases, in both the medial and lateral menisci. The mean classical Bonar score was 8.3571 and the mean modified Bonar score was 6.9398. There were no statistically significant differences in classical Bonar score assessment between medial and lateral menisci (p = 0.3014). There were no statistically significant differences in the modified-Bonar score assessment between medial and lateral menisci (p = 0.3620). We show that both menisci are implicated in the degenerative process, with high scores in the Bonar system, regardless of knee axial deformity. The Bonar score, along with its modifications, can be readily employed in the microscopic assessment of meniscus pathology.

Effect of the Material Properties and Knee Position to the Bone Bruise Pattern in Skeletally Mature and Immature Subjects.

A bone bruise is generated by a bony collision that could occur when the ACL is injured, and its pattern supposedly depends on the injury mechanism and level of skeletal maturity. The objective of this study was to determine the effect of material properties and knee position on the bone bruise pattern in skeletally mature and immature subjects using finite element analysis. Finite element models were created from an MR image in the sagittal plane of a skeletally mature and immature male subject. The femur and tibia were collided at 2 m/s to simulate the impact and determine the maximum principal stress. The analysis was performed at 15, 30 and 45 degrees of knee flexion, and neutral, 10 mm anterior and posterior translated position at each flexion angle. Although high stress was distributed toward the metaphysis area in the mature model, the stress did not cross the growth plate in the immature model. The size of the stress area was larger in the mature model than those in the immature model. The location of the stress area was dependent on the joint position as well as Young's modulus of cartilage and trabecular bone. Thus, the bone bruise pattern was affected by the knee position and tissue quality. In conclusion, although the bone bruise distribution was generally called footprint of the injury, the combined evaluation of the quality of the structure and the bone bruise distribution is necessary for properly diagnosing tissue injury based on the MR imaging.

Mass Spectrometry Imaging of the Subchondral Bone in Osteoarthritis Reveals Tissue Remodeling of Extracellular Matrix Proteins that Precede Cartilage Loss.

Osteoarthritis (OA) of the knee is a degenerative condition of the skeletal extracellular matrix (ECM) marked by the loss of articular cartilage and subchondral bone homeostasis. Treatments for OA in the knee beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers of disease. Here, Mass Spectrometry Imaging (MSI) enabled molecular spatial mapping of the proteomic landscape of human knee tissues. Histologic sections of human tibial plateaus from OA patients and cadaveric controls were treated with collagenase III to target ECM proteins prior to imaging using a timsTOF fleX mass spectrometer (Bruker) for matrix-assisted laser desorption ionization (MALDI)-MSI of bone and cartilage proteins in human knees. Spatial MSI data of the knee, using sections of the tibial plateau from non-arthritic, cadaveric donors or from knee replacement patients with medial OA were processed and automatically segmented identifying distinct areas of joint damage. ECM peptide markers compared either OA to cadaveric tissues or OA medial to OA lateral. Not only did candidate peptides distinguish OA relative to intact cartilage, but also emphasized a significant spatial difference between OA and intact subchondral bone (AUROC >0.85). Overall, 31 peptide candidates from ECM proteins, including COL1A1, COL3A1, and unanticipated detection of collagens COL6A1 and COL6A3 in adult bone, exhibited significantly elevated abundance in diseased tissue. Highly specific hydroxyproline-containing collagens dominated OA subchondral bone directly under regions of lost cartilage revealing dramatic tissue remodeling providing molecular details on the progression of joint degeneration in OA. The identification of specific spatial markers for the progression of subchondral bone degeneration in OA advances our molecular understanding of coupled deterioration of joint tissues.

Autofluorescence-based tissue characterization enhances clinical prospects of light-sheet-microscopy

Light sheet fluorescence microscopy (LSFM) is a transformative imaging method that enables the visualization of non-dissected specimen in real-time 3D. Optical clearing of tissues is essential for LSFM, typically employing toxic solvents. Here, we test the applicability of a non-hazardous alternative, ethyl cinnamate (ECi). We comprehensively characterized autofluorescence (AF) spectra in diverse murine tissues—ocular globe, knee, and liver—employing LSFM under various excitation wavelengths (405–785 nm) to test the feasibility of unstained samples for diagnostic purposes, in particular regarding percutaneous biopsies, as they constitute to most harvested type of tissue sample in clinical routine. Ocular globe structures were best discerned with 640 nm excitation. Knee tissue showed complex variation in AF spectra variation influenced by tissue depth and structure. Liver exhibited a unique AF pattern, likely linked to vasculature. Hepatic tissue samples were used to demonstrate the compatibility of our protocol for antibody staining. Furthermore, we employed machine learning to augment raw images and segment liver structures based on AF spectra. Radiologists rated representative samples transferred to the clinical assessment software. Learning-generated images scored highest in quality. Additionally, we investigated an actual murine biopsy. Our study pioneers the application of AF spectra for tissue characterization and diagnostic potential of optically cleared unstained percutaneous biopsies, contributing to the clinical translation of LSFM.

Duration of cefazolin prophylaxis did not impact infection risk in a murine model of joint arthroplasty.

To minimize periprosthetic joint infection (PJI) risk, some clinicians prescribe extended antibiotic prophylaxis (EAP) following total joint arthroplasty (TJA). Given the limited evidence supporting EAP, we sought to evaluate impact of prophylactic antibiotic duration on PJI risk in a murine TJA model. A titanium prosthesis was implanted into the proximal tibia of 89 mice and inoculated with 102 colony forming units (cfu) of Staphylococcus aureus Xen36. Control mice (n = 20) did not receive antibiotics. Treated mice received either 24 h (n = 35) or 4 days (n = 34) of cefazolin prophylaxis. Cultures were obtained from the prostheses, tibia, femur, and knee tissues 3 weeks after surgery. All mice in the control group developed PJI. Both prophylaxis regimens reduced the rate of PJI relative to the control, with only 2/35 mice in the 24-h cohort (p < 0.0001) and 1/34 in 4-day cohort developing PJI (p < 0.0001). CFU counts from the prostheses, bone and knee tissues were reduced for the 24-h and 4-day prophylaxis cohorts relative to the control (p < 0.0001 for both). There was no difference in rates of PJI or CFU counts between the two prophylaxis cohorts (p = 0.58). Prophylactic cefazolin profoundly reduced rates of PJI in a murine model of TJA in which all control animals developed PJI. Extending cefazolin prophylaxis duration from 24 h to 4 days did not result in improved PJI rates or decreased bacterial loads in infected cases. While these results strongly support use of antibiotic prophylaxis for TJA, EAP did not appear to add benefit in the described mouse model.

Incidence of Total Knee Arthroplasty After Arthroscopic Surgery for Knee Osteoarthritis

It is unclear whether arthroscopic resection of degenerative knee tissues among patients with osteoarthritis (OA) of the knee delays or hastens total knee arthroplasty (TKA); opposite findings have been reported. To compare the long-term incidence of TKA in patients with OA of the knee after nonoperative management with or without additional arthroscopic surgery. In this ad hoc secondary analysis of a single-center, assessor-blinded randomized clinical trial performed from January 1, 1999, to August 31, 2007, 178 patients were followed up through March 31, 2019. Participants included adults diagnosed with OA of the knee referred for potential arthroscopic surgery in a tertiary care center specializing in orthopedics in London, Ontario, Canada. All participants from the original randomized clinical trial were included. Data were analyzed from June 1, 2021, to October 20, 2022. Arthroscopic surgery (resection or debridement of degenerative tears of the menisci, fragments of articular cartilage, or chondral flaps and osteophytes that prevented full extension) plus nonoperative management (physical therapy plus medications as required) compared with nonoperative management only (control). Total knee arthroplasty was identified by linking the randomized trial data with prospectively collected Canadian health administrative datasets where participants were followed up for a maximum of 20 years. Multivariable Cox proportional hazards regression models were used to compare the incidence of TKA between intervention groups. A total of 178 of 277 eligible patients (64.3%; 112 [62.9%] female; mean [SD] age, 59.0 [10.0] years) were included. The mean (SD) body mass index was 31.0 (6.5). With a median follow-up of 13.8 (IQR, 8.4-16.8) years, 31 of 92 patients (33.7%) in the arthroscopic surgery group vs 36 of 86 (41.9%) in the control group underwent TKA (adjusted hazard ratio [HR], 0.85 [95% CI, 0.52-1.40]). Results were similar when accounting for crossovers to arthroscopic surgery (13 of 86 [15.1%]) during follow-up (HR, 0.88 [95% CI, 0.53-1.44]). Within 5 years, the cumulative incidence was 10.2% vs 9.3% in the arthroscopic surgery group and control group, respectively (time-stratified HR for 0-5 years, 1.06 [95% CI, 0.41-2.75]); within 10 years, the cumulative incidence was 23.3% vs 21.4%, respectively (time-stratified HR for 5-10 years, 1.06 [95% CI, 0.45-2.51]). Sensitivity analyses yielded consistent results. In this secondary analysis of a randomized clinical trial of arthroscopic surgery for patients with OA of the knee, a statistically significant association with delaying or hastening TKA was not identified. Approximately 80% of patients did not undergo TKA within 10 years of nonoperative management with or without additional knee arthroscopic surgery. ClinicalTrials.gov Identifier: NCT00158431.

In Situ Loading and Time-Resolved Synchrotron-Based Phase Contrast Tomography for the Mechanical Investigation of Connective Knee Tissues: A Proof-of-Concept Study.

Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time-resolved synchrotron-based X-ray phase-contrast tomography (SR-PhC-µCT) allows to capture the tissue dynamics. This proof-of-concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR-PhC-µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress-relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases.

Comparison of the effects of different foam rolling durations on knee extensors function.

Foam rolling (FR) intervention has recently attracted attention in sports and rehabilitation settings. However, the effects of FR using different rolling durations have not been fully clarified. Thus, this study focused on FR durations and examined the acute and prolonged (i.e., 20-min; 40-min, 60-min) effects of different FR intervention durations on maximal voluntary concentric contractions (MVC-CON), knee flexion range of motion (ROM), pain pressure threshold (PPT), and tissue hardness. The participants were 10 male university students (22.5 ± 1.0 years), and the target muscles were the dominant leg knee extensors. Three sets of 60-seconds FR interventions were performed in the randomized crossover trials in each condition. The three intervention conditions were fast (1 rolling/2 s, 30-repetition × 3 sets, 90 repetitions), medium (1 rolling/6 s, 10-repetition × 3 sets, 30 repetitions), and slow speed (1 rolling/12 s, 5-repetition × 3 sets, 15 repetitions). Before as well as immediately, 20-min, 40-min, and 60-min after the interventions, MVC-CON, ROM PPT, and tissue hardness were measured. The results showed no interaction effect in the acute effect but a main effect of time for all variables (p < 0.05). Also, no interaction was observed in prolonged effect, but main effects of time were observed in knee flexion ROM, PPT, and tissue hardness (p < 0.01) but not for MVC-CON. Post-hoc tests showed significant PPT (p < 0.05) and knee flexion ROM (p < 0.01) increases up to 20- and 60-minutes respectively after all interventions. Tissue hardness was significantly (p < 0.01) decreased up to 60-minutes after all interventions. This study showed that the FR intervention changed ROM, PPT, tissue hardness, and MVC-CON regardless of rolling duration and that the effects persisted up to 20-60 minutes.

Comparison of acute and prolonged effects of short-term foam rolling and vibration foam rolling on the properties of knee extensors.

Recently, Foam Rolling (FR) and Vibration Foam Rolling (VFR) have attracted attention in sports and rehabilitation fields. Previous studies have shown that FR and VFR acute interventions effectively increase the range of movement (ROM) and decrease tissue hardness. For application to sports and rehabilitation, it is necessary to compare the acute and prolonged effects of short duration FR and VFR. Therefore, this study aimed to compare and investigate the acute and prolonged (15 minutes) effects of short duration (30-s) FR and VFR interventions on knee extensors. The subjects were 14 male university students (22.4 ± 1.0 years old), in which the knee extensors of the dominant leg were tested. In a cross-over trial, 30-s of FR or VFR were performed with 2-s rolling of the anterior thigh (15 rolls). The frequency of VFR was 35 Hz. Measurements included knee flexion ROM, pain pressure threshold (PPT), tissue hardness, and countermovement jump height. The results of this study showed no interaction effects for all variables, but main time effects were observed for knee flexion ROM, PPT, and tissue hardness. Post-hoc tests showed that knee flexion ROM increased up to 10 minutes after the intervention. PPT significantly increased, and tissue hardness significantly decreased up to 15 minutes after intervention. This study showed that 30-s FR and VFR interventions effectively increased ROM, PPT, and decreased tissue hardness. The effects were prolonged up to 10-15 minutes after the intervention. The results of this study show no advantage of VFR over FR with acute short-term interventions.

Inflammatory synovial biomarkers and state of the tibiofemoral joint in the post-surgical settings: a narrative review.

Knee surgery attempts to restore the native biomechanics of the knee, improve stability, and decrease the progression of osteoarthritis (OA). However, despite improvements in surgical techniques, tissue degradation and OA are common after knee surgery, occurring in higher rates in surgical knees compared to non-surgical knees. The aim of this study is to analyze previous literature to determine which synovial fluid biomarkers contribute to knee tissue degradation and decrease patient outcomes in the post-surgical setting of the knee. A narrative review of relevant literature was performed in July 2023. Studies reporting on synovial biomarkers associated with the post-surgical knee were included. The literature reported that proinflammatory synovial biomarkers cause cartilage degradation and turnover which eventually leads to OA. The associated biomarkers are typically present prior to physical symptoms so understanding which one's correlate to OA is important for potential therapeutic treatments in the future. Studying the preoperative, early postoperative, and late postoperative synovial biomarkers will allow physicians to develop an improved understanding of how these biomarkers progress and correlate to knee tissue degradation and OA. This understanding could lead to further developments into potential treatment options. Research into inhibiting or reversing these inflammatory biomarkers to slow the progression of knee tissue degradation has already begun and has reported some promising results but is currently limited in scope. Synovial fluid biomarkers in the post-surgical knee setting may contribute to decreased patient outcomes and the progression of knee tissue degradation. There is no current consensus on which of these biomarkers are the most detrimental or associated with decreased patient outcomes. With an improved understanding of the individual biomarkers, potential personalized therapeutic treatment could be used by physicians in the future to improve patient outcomes after surgery.

Assessment of Pedestrians' Head and Lower Limb Injuries in Tram-Pedestrian Collisions.

Analysis of pedestrians' head and lower limb injuries at the tissue level is lacking in studies of tram-pedestrian collisions. The purpose of this paper therefore to investigate the impact response process and severity of pedestrians' injuries in tram-pedestrian collisions, using the Total Human Model for Safety (THUMS) pedestrian human body model together with the tram FE model. Two full-scale tram-pedestrian dummy crash tests were performed to validate the FE model, and the total correlation and analysis (CORA) score of head acceleration yielded values of 0.840 and 0.734, confirming a strong agreement between the FE-simulated head responses and the experimental head kinematics. The effects of different tram speeds and impact angles on pedestrians' impact response injuries and the differences were further analyzed. The results indicate that direct impact of the lower limb with the tram's obstacle deflector leads to lower limb bone shaft fractures and knee tissue damage. Neck fling contributed to worsened head injury. Coup contusions were the predominant type of brain contusion, surpassing contrecoup contusions, while diffuse axonal injury was mainly concentrated in the collision-side region of the brain. Pedestrians' injuries are influenced by tram velocity and impact angle: higher tram velocities increase the risk of lower limb and head injuries. The risk of head injury for pedestrians is higher when the impact angle is negative, while lower limb injuries are more significant when the impact angle is 0°. This study provides practical guidance for enhancing tram safety and protecting pedestrians.

AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFβ1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFβ1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

MiR-203a-3p attenuates apoptosis and pyroptosis of chondrocytes by regulating the MYD88/NF-κB pathway to alleviate osteoarthritis progression.

Osteoarthritis (OA) is a degenerative joint disease that imposes a significant socioeconomic burden worldwide. Our previous studies revealed a down-regulation of miR-203a-3p in the knee tissues of OA patients. However, the underlying mechanism through which miR-203a-3p mediates the pathological process of OA remains unknown. Thus, we aimed to determine the effects of miR-203a-3p in the progression of OA. Rat primary chondrocytes were stimulated with 10 μg/mL lipopolysaccharide (LPS) for 24 hours, followed by transfection with 50 nM miR-203a-3p mimic, inhibitor, and siRNA for MYD88 or consistent negative controls for 48 hours. To evaluate the effects of miR-203a-3p on cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis in chondrocytes, various techniques such as immunofluorescence staining, biochemical analysis, Western blotting, and the TUNEL staining were utilized. In the rat OA model, all rats were randomly divided into four groups: Sham, OA, OA+Agomir negative control (NC), and OA+Agomir. They received intra-articular injections of 25 nmol miR-203a-3p agomir, agomir NC, or normal saline twice a week for the duration of 8 weeks after OA induction. Immunofluorescence staining was performed to evaluate the effects of miR-203a-3p on cartilage matrix degradation in rats. MiR-203a-3p was down-regulated in LPS-treated rat chondrocytes and OA cartilage, and directly targeted MYD88. Moreover, miR-203a-3p significantly inhibited LPS-induced cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis of chondrocytes via targeting MYD88. Mechanistically, miR-203a-3p exerted protective effects via the inhibition of the MYD88/NF-κB pathway. In the rat OA model, intra-articular injections of miR-203a-3p agomir also significantly inhibited cartilage matrix degradation, thereby alleviating OA progression. Furthermore, the miR-203a-3p agomir-treated arthritic rat dramatically exhibited better articular tissue morphology and lower OARSI scores. MiR-203a-3p plays a role in alleviating the progression of OA by regulating the MYD88/NF-κB pathway, thereby inhibiting cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis of chondrocytes. It highlights the potential significance of miR-203a-3p as an important regulator of OA.

Biomechanical analysis of statics and gait of patients with patellofemorale pain syndrome

Patellofemoral pain syndrome (PFPS) is a pathology in the knee joint, which is often observed in young active people and manifests itself as pain in the knee and periarticular tissues in the absence of intra-articular pathology of the knee joint. The article presents the results of a biomechanical study of statics and walking in 47 patients with PFPS and 34 healthy individuals. Differences in goniometric parameters were revealed in patients and healthy individuals when walking. It has been demonstrated that in PFPS, biome-chanical disturbances affect both lower extremities. It has been shown that the severity of biomechanical disorders when walking can serve as a predictor of the effectiveness of conservative therapy for PFPS.

Assessment of ultrashort echo time (UTE) T2* mapping at 3T for the whole knee: repeatability, the effects of fat suppression, and knee position.

Knee tissues such as tendon, ligament and meniscus have short T2* relaxation times and tend to show little to no signal in conventional magnetic resonance acquisitions. An ultrashort echo time (UTE) technique offers a unique tool to probe fast-decaying signals in these tissues. Clinically relevant factors should be evaluated to quantify the sensitivity needed to distinguish diseased from control tissues. Therefore, the objectives of this study were to (I) quantify the repeatability of UTE-T2* relaxation time values, and (II) evaluate the effects of fat suppression and (III) knee positioning on UTE-T2* relaxation time quantification. A dual-echo, three-dimensional center-out radially sampling UTE and conventional gradient echo sequences were utilized to image gadolinium phantoms, one ex-vivo specimen, and five in-vivo subjects on a clinical 3T scanner. Scan-rescan images from the phantom and in-vivo experiments were used to evaluate the repeatability of T2* relaxation time values. Fat suppressed and non-suppressed images were acquired for phantoms and the ex-vivo specimen to evaluate the effect of fat suppression on T2* relaxation time quantifications. The effect of knee positioning was evaluated by imaging in-vivo subjects in extended and flexed positions within the knee coil and comparing T2* relaxation times quantified from tissues in each position. Phantom and in-vivo measurements demonstrated repeatable T2* mapping, where the percent difference between T2* relaxation time quantified from scan-rescan images was less than 8% for the phantom and knee tissues. The coefficient of variation across fat suppressed and non-suppressed images was less than 5% for the phantoms and ex-vivo knee tissues, showing that fat suppression had a minimal effect on T2* relaxation time quantification. Knee position introduced variability to T2* quantification of the anterior cruciate ligament, posterior cruciate ligament, and patellar tendon, with percent differences exceeding 20%, but the meniscus showed a percent difference less than 10%. The 3D radial UTE sequence presented in this study could potentially be used to detect clinically relevant changes in mean T2* relaxation time, however, reproducibility of these values is impacted by knee position consistency between scans.

Acute Effects of Different Foam Roller Intervention Techniques on Knee Extensors.

The usefulness of Foam Roller (FR) even without a rolling stimulus (e.g., static compression with or without dynamic joint movements) has been recently demonstrated; however, the different effects of these methods remain unclear. Thus, this study aimed to compare and investigate the effects of such FR intervention methods on knee extensors. The dominant knee extensors of 20 male university students were investigated using the following four conditions: control (CON), FR with rolling (FR_rolling), FR with static compression (FR_SC), and FR with static compression + dynamic movement of the knee joint (FR_DM). FR_SC was intervened to compress the muscle belly of the knee extensors. FR_DM involved knee flexion and extension while maintaining the FR_SC condition. Knee flexion ROM, pain pressure threshold (PPT), tissue hardness, and countermovement jump (CMJ) height were outcome variables; they were compared before and immediately after the intervention. The results of this study showed that knee flexion ROM was significantly (p < 0.01) increased in FR_rolling (d = 0.38), FR_SC (d = 0.28), and FR_DM (d = 0.64). Tissue hardness was significantly (p < 0.01) decreased in FR_rolling (d = -0.55), FR_SC (d = -0.28), and FR_DM (d = -0.42). A main effect of time (p < 0.01) was observed in knee flexion ROM, PPT, and tissue hardness, but no change in CMJ was observed. The results of this study suggested that clinicians and athletes could choose any method they like as a warm-up routine.

Incidence of Focal Osteolysis in a Titanium Limb-Lengthening Device: A Comparison to a Stainless-Steel Model

Objectives: To evaluate 1 manufacturer's titanium intramedullary lengthening nail (ILN) for radiographic evidence of adverse tissue reactions similar to those in their stainless-steel ILN that was recalled in 2021, with specific outcomes of (1) incidence of periosteal reaction and osteolysis and (2) adverse tissue reaction-related device failures. Design: Radiographic review of consecutive patients with ≥1-year clinical follow-up who received 1 manufacturer's ILNs implanted in the femur and/or tibia from February 2012 to July 2021. Setting: Single tertiary-care center. Patients/Participants: Two hundred twenty-six limbs with titanium ILNs and 57 limbs with stainless-steel ILNs. Intervention: Precice titanium ILN (NuVasive Specialized Orthopedics, San Diego, CA) and Stryde stainless-steel ILN (NuVasive Specialized Orthopedics). Main Outcome Measurements: Radiographic outcome data and complications. Results: Of 226 limbs with titanium ILNs, 160 (70.8%) had periosteal reaction, and 2 (0.9%) had osteolysis. Periosteal reaction and osteolysis rates in stainless-steel ILNs (57 limbs) were 39% and 26%, respectively. No adverse tissue reaction-related device failures were noted with titanium. Several other complications presented, notably hip and/or knee tissue contracture (141), consolidation problems (8), and needing peroneal nerve decompression (14). Conclusions: Osteolysis incidence was substantially less among the titanium population, supporting the claim that observed osteolysis in the stainless-steel cohort was attributed to its construct. On average, periosteal reaction was radiographically appreciated later in patients with titanium than stainless steel. Further study is needed to confirm this finding. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Synovial fluid exosome-derived miR-182-5p alleviates osteoarthritis by downregulating TNFAIP8 and promoting autophagy through LC3 signaling

ObjectiveTo investigate the role of exosomal miRNAs from synovial fluid (SF) in osteoarthritis (OA) patients and investigate the underlying molecular mechanism. MethodsDegenerated knee tissues were collected from male and female OA patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the differences in the expression of inflammatory indicators, including TNF-α, IL-6, and IL-10, between the degenerative and injury groups. Exosomes were isolated from SF using the Exoquick kit, and a microarray was used to identify differentially expressed miRNAs (DEmiRNAs), which were analyzed using bioinformatics. The predicted relationship between DEmiRNAs and target genes was verified using a luciferase reporter gene assay. CCK-8 and transwell assays were used to assess cell viability and migration. Immunofluorescence and TUNEL assay were used to detect cell autophagy and apoptosis. The interaction between proteins was detected by immunoprecipitation and verified by Mab rescue assay. ResultsThe relative expression of TNF-α/IL6 was significantly higher in the degeneration group than in the injury group. The OA degeneration group released significantly more and smaller exosomes than the injury group. The expression of miR-182-5p was markedly reduced in OA patients and had a higher correlation with inflammatory indicators. Tumor necrosis factor α-induced protein 8 (TNFAIP8) was a target of miR-182-5p, and its overexpression promoted chondrocyte proliferation, migration, and invasion and enhanced the wound healing efficiency. We also found a direct interaction of TNFAIP8 with autophagy-related gene 3 (ATG3). TNFAIP8 triggered ATG3 LC3-mediated autophagy. ConclusionThe downregulation of exosomal miR-182-5p inhibits OA degeneration by targeting TNFAIP8 via the ATG/LC3 pathway.

Bacterial DNA and osteoarthritis in dogs with patellar luxation and cranial cruciate ligament rupture.

The association between bacterial DNA in stifle joints, including those with cranial cruciate ligament rupture (CCLR) and medial patellar luxation (MPL), and osteoarthritis in dogs remains elusive. This study investigated the potential association between the detection of bacterial DNA and osteoarthritis in dogs using a broad-range polymerase chain reaction technique targeting the 16S ribosomal RNA gene. Synovial fluid (35 samples) and knee tissue samples (32 samples) were obtained from 35 dogs diagnosed with CCLR (n = 20; 11 males and nine females) or MPL (n = 15; five males and 10 females) who underwent a surgical operation between October 2014 and April 2015. Dogs with CCLR had a higher average osteoarthritis score than those with MPL (2.0 ± 0.9 vs. 0.5 ± 0.9; p = 0.005). Bacterial DNA was detected in the stifle joints of 60.71% of dogs with MPL. Pelomonas spp. (25.00%), Halomonas spp. (17.86%), and 5 other species (17.86%) were the most frequently identified bacteria. Bacterial DNA was detected in 41.03% of dogs with CCLR. Pelomonas spp. (15.38%), Sphingomonas spp. (10.26%), Halomonas spp. (5.13%), and 4 other species (10.26%) were the most frequently identified bacteria. No significant difference was observed in the prevalence of bacterial DNA obtained from tissue samples (46.88%) or joint fluid samples (51.43%). The presence of bacterial DNA was not associated with the type of knee injury (MPL or CCLR; p = 1.000). There was a higher prevalence of bacterial DNA in samples from dogs with moderate-to-severe osteoarthritis (94.44%) than in those with minimal osteoarthritis (41.18%), and a significant association between the presence of bacterial DNA and moderate-to-severe osteoarthritis was identified (p < 0.01). Dogs with moderate-to-severe osteoarthritis were more likely to have bacterial DNA in their stifle joints than those with no or minimal osteoarthritis. These findings provide valuable insight into the potential role of bacterial DNA in joint tissue or joint fluid and the development of osteoarthritis in dogs.

High-Sucrose Diet Accelerates Arthritis Progression in a Collagen-Induced Rheumatoid Arthritis Model.

High dietary sugar and sweeteners are suspected to cause the development of rheumatoid arthritis (RA) symptoms through the induction of proinflammatory cytokine release. However, the mechanisms by which increased dietary sugar affects RA etiology are not yet fully understood. The study uses a mouse model of collagen-induced RA (CIA) to investigate the relationship between excessive sugar consumption and RA risk. RA-associated pathological features are assessed in the nonimmunized (NI) control group, the CIA-positive control group, and the CIA + high-sucrose diet (CIA+HS, 63% calories from sucrose) group. Compared with the CIA group, the CIA+HS group shows a greater increase in paw thickness and clinical scores, as well as, a higher degree of pannus formation and inflammation in the knee, ankle, and sole tissues. Moreover, the infiltration of immune cells is increased in the CIA+HS group. Although the expression of hepatic lipogenic genes, is not altered, that of toll-like receptor (TLR4) and IL-1β is considerably elevated in the CIA+HS group. These findings suggest that excessive sucrose consumption causes hepatic fibrosis and inflammation, contributing to the pathophysiology of RA.