Healthy Joints Research Articles

Effects of intra-articular injection of an acellular equine liquid amniotic allograft in healthy equine joints.

Evaluate effects of acellular equine liquid amnion allograft (ELAA) injected into healthy equine joints. Randomized, blinded, controlled experiment. Eight healthy adult horses. One intercarpal joint (ICJ) of each horse was randomly assigned to be injected with 1.5ml of ELAA (treatment) while the contralateral ICJ was injected with 1.5ml of 0.9% NaCl (control). Subjective lameness evaluation, force plate analysis, and synovial fluid analysis, including interleukin-1 receptor antagonist (IL-1ra) analysis, were performed before (day 0) and at days 1, 3, 5, and 10. Synovial fluid analysis was also performed on days 20 and 30. No difference in subjective lameness (P=.75) and no decrease in peak vertical force or vertical impulse were seen in any limb on any day. Total nucleated cell count (TNCC) was increased in treatment joints on days 1 (P=.0007; T: 6039 cells/μl, C: 240 cells/μl) and 3 (P < .0001; T: 1119 cells/μl, C: 240 cells/μl). Log-10 transformed values for IL-1ra were higher in treated joints on days 1 (P=.0005; T: 3553.7pg/ml, C: 1890.1pg/ml) and 3 (P=.01; T: 2283.2pg/ml, C: 1250.7pg/ml). Injection of ELAA into the ICJ caused an increase in synovial fluid TNCC in comparison with saline control but no lameness was observed. There was increased IL-1ra on days 1 and 3 after ELAA injection. Intra-articular injection of ELAA into healthy equine joints results in no significant safety concerns. The observed increase in IL-1ra may provide beneficial effects in inflamed joints.

Identification of Defective Joints in Beams via Torsional Vibration

The determination of the shear dynamic modulus in wood product panels is of greater importance than its determination in wood beams. Yet with regards to the effect of defects on the obtained values of shear modulus, this factor is used to detect the defects and the degree of the defects. In this study, the effect of gluing defects in two joint shapes (scarf (45°) and finger joints (10 mm length and 3 mm pitch) were evaluated non-destructively using the torsional vibration method. Rectangular wood specimens with dimensions of 20 mm × 40 mm × 360 mm (R × T × L) were prepared from clear eastern beech. The joints were located at similar positions in the middle of the beams. The results showed that creating a healthy joint did not significantly change the values obtained for the shear modulus in either of the joint shapes. However, reducing the adhesion level in both types of joints caused a significant reduction in the shear modulus values. The results show that the changes in the dynamic shear modulus values in both joint types, as a result of changes in the glue coverage rating (fully, medium and low-glued joints) allows the detection of the defects as well as the degree of the defects.

Wearable knee joint fatigue estimating system based on curvature and pressure sensing.

The injury of the knee joint is found to be directly related to the fatigue caused by excessive exercise. Many previous studies used wearable devices to measure the angle of knee joint during activities, but did not pay enough attention to the load of knee joint related to the fatigue degree of it. A wearable embedded system was designed to sense the motion state and load of knee joint and uses the sensoring data to estimate and predict the fatigue degree of knee joint during exercise in real time, so as to prevent it from being injured. An economical wearable system is designed to measure the parameters of the knee joint during exercises. Then the warning message and recommended healthy lasting time are able to be sent to users to avoid excessive exercise. 24 healthy volunteers aged 20-25 years were involved in the experiments. Two famous evaluation scales for knee joint from Department of Orthopedics (Lysholm score and IKDC score) were adopted to evaluate the protective effect. After 14 days of the first stage testing, all the participants with wearable devices reported healthy knee joint state to verify the effectiveness of the system. For the second stage, the testing group equipped with wearable warning devices did not receive obvious change in the two scales. However, Lysholm score of control group dropped by at least 7.4 and IKDC score dropped by at least 11.1 which were significantly reduced. Only using human perception to prevent knee joint fatigue had a risk of failure while the designed wearable system could protect the knee successfully from injuries during exercises, such as running, badminton, table tennis and basketball. Moreover, female gender and a high BMI value may be two factors that increase the risk of knee injuries during sports.

Hip osteoarthritis: A novel network analysis of subchondral trabecular bone structures.

Hip osteoarthritis (HOA) is a degenerative joint disease that leads to the progressive destruction of subchondral bone and cartilage at the hip joint. Development of effective treatments for HOA remains an open problem, primarily due to the lack of knowledge of its pathogenesis and a typically late-stage diagnosis. We describe a novel network analysis methodology for microcomputed tomography (micro-CT) images of human trabecular bone. We explored differences between the trabecular bone microstructure of femoral heads with and without HOA. Large-scale automated extraction of the network formed by trabecular bone revealed significant network properties not previously reported for bone. Profound differences were discovered, particularly in the proximal third of the femoral head, where HOA networks demonstrated elevated numbers of edges, vertices, and graph components. When further differentiating healthy joint and HOA networks, the latter showed fewer small-world network properties, due to decreased clustering coefficient and increased characteristic path length. Furthermore, we found that HOA networks had reduced length of edges, indicating the formation of compressed trabecular structures. In order to assess our network approach, we developed a deep learning model for classifying HOA and control cases, and we fed it with two separate inputs: (i) micro-CT images of the trabecular bone, and (ii) the network extracted from them. The model with plain micro-CT images achieves 74.6% overall accuracy while the trained model with extracted networks attains 96.5% accuracy. We anticipate our findings to be a starting point for a novel description of bone microstructure in HOA, by considering the phenomenon from a graph theory viewpoint.

Study of a Passive Orthosis for Reducing the Load Transfer in the Hip Joint

There are several orthoses that allow for the assistance of movement on the lower limbs, mainly flexion–extension. However, there is still a lack of systems that allow, in addition to assisting movement, for transferring the load from weakened anatomical parts to physically healthy joints. A model of a passive and light orthosis that is capable of transferring part of the load from the hip joint directly to the body of the femur was developed and tested. This helps to attenuate the longitudinal component of the force, thus reducing pain and the patient’s discomfort. Computer-aided design (CAD) models and numerical studies were conducted using an offline model of the hip forces, and a proof-of-concept prototype was also developed for experimental validation. The model uses a rigid ergonomic structure and an elastic energy-accumulating device, in this case, a spring, whose preload can be regulated for controlling the assistance’s level. The numeric simulations demonstrated the adequacy of the model for a spring pre-load of 20% of the force applied to the femoral head, reducing the load in the hip joint. The hypothesis of the present study, that the orthosis can reduce the reaction load on the hip joint, was validated by the computational model developed and by the preliminary experimental results obtained with the concept prototype. The approached model represents a promising starting point for subsequent studies and progression for the practical and clinical field.

Interleukin-6 neutralization and regulatory T cells are additive in chondroprotection from IL-1β-induced inflammation.

Anti-inflammatory Regulatory T cells (Tregs) are enriched in the joints of patients with osteoarthritis (OA) compared to healthy joints. Tregs maintain homeostasis through secretion of anti-inflammatory cytokines and cell-to-cell interactions including immune checkpoint signaling. Interleukin-6 (IL-6) is a pleiotropic cytokine secreted by inflamed synoviocytes and chondrocytes that can inhibit or alter Treg function. This study tested the hypothesis that neutralization of IL-6 would enable Treg anti-inflammatory function to resolve inflammation and catabolism elicited by IL-1β in an equine chondrocyte/synoviocyte/Treg tri-culture OA model. Synoviocyte/chondrocyte co-cultures were stimulated with IL-1β, and treated with αIL-6 neutralizing antibody. Activated Tregs secreting IL-10 were added in direct contact with synoviocytes to create a tri-culture. Neutralization of IL-6 partially restored Treg anti-inflammatory functions and, in combination, reduced IL-1β-stimulated synoviocyte MMP13 expression to control levels and restored Acan expression in chondrocytes. IL-6 neutralization alone decreased Il6 expression in chondrocytes and synoviocytes, mitigating IL-6 positive feedback loop. Although Tregs were the primary producers of anti-inflammatory IL-10 and IL-4, they also produced pro-inflammatory IL-17A, as detected by ELIA, which may have been responsible for incomplete rescue of synoviocyte/chondrocyte homeostasis following IL-1β stimulation. Treg secretion of IL-10, IL-4, and IL-17A was not altered by tri-culture conditions or presence of αIL-6, therefore, it was unlikely that Treg phenotype instability occurred. The significant effect of chondrocyte/synoviocyte donor, but not Treg donor, on gene expression and IL-6 concentration in conditioned media, indicated that personalized therapy considering the patient's OA status might be needed for successful implementation of immunotherapy in the context of OA.

Influence of hyaluronic acid on intra-articular friction – a biomechanical study in whole animal joints

BackgroundCartilage is a mechanically highly stressed tissue in the human body and an important part of synovial joints. The joint cartilage is lubricated by synovial fluid with hyaluronic acid (HA) as main component. However, in joints with osteoarthritis HA has a lower concentration and molecular weight compared to healthy joints. In recent years, the intra-articular injection of therapeutic HA lubricant, has become a popular therapy. The effect of HA application on the friction of a complete joint with physiological movement needs to be further determined.MethodsThe aim of the present study was to evaluate the lubrication effect of the joint by three lubricants (NaCl, fetal calf serum (FCS) and HA) and their effect on the friction in nine complete ovine carpo-metacarpal joints. The joints were mounted on a material testing machine and a physiological movement with 10° rotation was simulated with ascending axial load (100 – 400 N). Specimens were tested native, with cartilage damage caused by drying out and relubricated. Dissipated energy (DE) as a measure of friction was recorded and compared.ResultsInvestigating the effect of axial load, we found significant differences in DE between all axial load steps (p < .001), however, only for the defect cartilage. Furthermore, we could document an increase in DE from native (Mean: 15.0 mJ/cycle, SD: 8.98) to cartilage damage (M: 74.4 mJ/cycle, SD: 79.02) and a decrease after relubrication to 23.6 mJ/cycle (SD: 18.47). Finally, we compared the DE values for NaCl, FCS and HA. The highest values were detected for NaCl (MNorm = 16.4 mJ/cycle, SD: 19.14). HA achieved the lowest value (MNorm = 4.3 mJ/cycle, SD: 4.31), although the gap to FCS (MNorm = 5.1 mJ/cycle, SD: 7.07) was small.ConclusionsWe were able to elucidate three effects in joints with cartilage damage. First, the friction in damaged joints increases significantly compared to native joints. Second, especially in damaged joints, the friction increases significantly more with increased axial load compared to native or relubricated joints. Third, lubricants can achieve an enormous decrease in friction. Comparing different lubricants, our results indicate the highest decrease in friction for HA.

Vascular supply of the metacarpophalangeal joint.

To describe in detail the arterial vasculature of metacarpophalangeal joints 2-5 on cadaver specimens and to compare it to ultrasound imaging of healthy subjects. Eighteen hands of donated human cadavers were arterially injected and investigated with either corrosion casting or cryosectioning. Each layer of cryosectioned specimens was photographed in high-resolution. Images were then segmented for arterial vessels of the metacarpophalangeal (MCP) joints 2-5. The arterial pattern of the joints was reconstructed from the segmented images and from the corrosion cast specimens. Both hands of ten adult healthy volunteers were scanned focusing on the vasculature of the same joints with high-end ultrasound imaging, including color Doppler. Measurements were made on both cryosectioned arteries and Doppler images. The arterial supply of MCP joints 2-5 divides into a metacarpal and a phalangeal territory, respectively. The metacarpal half receives arteries from the palmar metacarpal arteries or proper palmar digital arteries, while the phalangeal half is supplied by both proper and common palmar digital arteries. Comparing anatomical and ultrasonographic results, we determined the exact anatomic location of normal vessels using Doppler images acquired of healthy joints. All, except three branches, were found with less than 50% frequency using ultrasound. Doppler signals were identified significantly more frequently in MCP joints 2-3 than on 4-5 (p < 0.0001). Similarly, Doppler signals differed in the number of detectable small, intraarticular vessels (p < 0.009), but not that of the large extraarticular ones (p < 0.1373). When comparing measurements acquired by ultrasound and on cadaver vessels, measurements using the former technique were found to be larger in all joints (p < 0.0001). Using morphological and ultrasonographic techniques, our study provides a high-resolution anatomical maps and an essential reference data set on the entire arterial vasculature of healthy human MCP 2-5 joints. We found that Doppler signal could be detected in less than 50% of the vessels of healthy volunteers except three locations. Intraarticular branches were detected with ultrasound imaging significantly more frequently on healthy MCP 2-3 joints, which should be taken into account when inflammatory and normal Doppler signals are evaluated. Our study also provides reference data for future, higher-resolution imaging techniques.

Assessment of 99mTc-NTP 15-5 uptake on cartilage, a new proteoglycan tracer: Study protocol for a phase I trial (CARSPECT).

Background99mTc-NTP 15-5 is a SPECT radiotracer targeting proteoglycans (PG), components of the cartilaginous extracellular matrix. Imaging of PGs would be useful for the early detection of cartilage disorders (osteoarthritis, arthritis and chondrosarcoma, Aromatase Inhibitor associated arthralgia (AIA) in breast cancer), and the follow-up of patients under treatment. According to preclinical study results, 99mTc-NTP 15-5, is a good candidate for a specific functional molecular imaging of joints. We intend to initiate a first in-human study to confirm and quantify 99mTc-NTP 15-5 uptake in healthy joints.MethodsAs the clinical development of this radiotracer would be oriented toward the functional imaging of joint pathologies, we have chosen to include patients with healthy joints (unilateral osteoarthritis of the knee or breast cancer with indication of AI treatment). This phase I study will be an open-label, multicenter, dose-escalation trial of a radiopharmaceutical orientation to determine the recommended level of activity of 99mTc-NTP 15-5 to obtain the best joint tracer contrasts on images, without dose limiting toxicity (DLT). The secondary objectives will include the study of the pharmacology, biodistribution (using planar whole body and SPECT-CT acquisitions), toxicity, and dosimetry of this radiotracer. The dose escalation with 3 activity levels (5, 10, and 15 MBq/kg), will be conditioned by the absence at the previous level of DLT and of a visualized tracer accumulation on more than 80% of healthy joints as observed on scintigraphy performed at ≤ 2 h post-injection.DiscussionThis first in-human phase I trial will be proof-of-concept of the relevance of 99mTc-NTP 15-5 as a cartilage tracer, with the determination of the optimal methodology (dose and acquisition time) to obtain the best contrast to provide a functional image of joints with SPECT-CT.Trial registration numberClinicaltrials.gov: NCT04481230. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2020-000495-37.

Development of a Method to Assess the Tribological Effect of Osteochondral Defects Within the Talocrural Joint

Category: Basic Sciences/Biologics; Ankle; Ankle Arthritis Introduction/Purpose: Osteochondral lesions of the talus commonly occur because of traumatic injury. These lesions can affect the biomechanical behaviour of the ankle joint resulting in further degradation of the tissue and development of osteoarthritis. However, little is known about the impact of such lesions to the biomechanical behaviour of the natural ankle joint, in particular changes to the tribology of the joint due to their introduction. The aim of this study was to develop a tribological simulation of the natural tibiotalar joint to assess frictional changes due to the introduction of chondral lesion and to further assess the impact of current treatment modalities such as AMIC techniques (Nanofracture with Chondro-Gide membrane) and osteochondral allograft cores (OCA). Methods: A healthy left cadaveric tibiotalar joint (n =1) was cemented into a custom-made jig; to preserve centre of rotation (COR). The sample was loaded into a ProSim Pendulum Friction simulator and tested using the following loading conditions. Simulations were run at 1-Hertz frequency for 3600 cycles with a constant load of 640 N applied through the tibia through a +- 10° flexion and extension (F/E) angle. Data was normalised using a mean frictional offset value calculated through a 2-minute pre- and post-test to account for additional frictional torque and changes to friction factor was assessed. Cartilage was assessed for changes in tissue appearance and damage. Following this, a 10-mm circular, chondral defect was introduced to talar dome and testing was repeated under the same conditions. The defect was repaired with a 10-mm Chondro-Gide patch and then 10-mm OCA before being subsequently tested using the same methods. Results: No visible changes were seen to the cartilage during testing for the healthy, defected and Chondro-Gide treated conditions. Some damage could be seen on the reciprocal tibial cartilage after testing with the OCA repair. Assessment of normalised friction factors showed that while testing, for each condition, the frictional output remained stable with a reduction in the mean friction factor seen due to the introduction of a defect. This was maintained with Chondro-Gide. A return to normal was seen in the OCA treatment with the overall mean values for the healthy and OCA repair were 0.0301 and 0.0329, respectively. In addition, overall mean frictional factor values in the presence of a defect and Chondro-Gide repair showed reduced frictional values of 0.0119 and 0.0103, respectively. Conclusion: This method will allow for potential preclinical evaluation of treatments for OLTs in an appropriately simulated environment to assess tribological changes. The values obtained for the frictional factor all sit within the expected range for friction between two cartilage surfaces that has been reported in the literature 0.003 and 0.08. Thus, providing a reliable platform for comparing different methods of osteochondral defect repair in the tibiotalar joint.

ОЦЕНКА ПРОПРИОЦЕПТИВНОЙ ФУНКЦИИ У ПАЦИЕНТОВ ПОСЛЕ ВОССТАНОВЛЕНИЯ ПЕРЕДНЕЙ КРЕСТООБРАЗНОЙ СВЯЗКИ

Abstract. Introduction. Recently, interest has been revived in the primary repair of the anterior cruciate ligament, which is largely due to the potential possibility of preserving its proprioceptive function. Aim. The aim of the study was to evaluate the proprioceptive function of the knee joint in patients who underwent anterior cruciate ligament repair with additional augmentation and to compare the results with similar parameters in patients who underwent anterior cruciate ligament reconstruction using semitendinosus muscle tendon. Material and methods. 40 patients were evaluated, who were divided into two groups: in group 1 (n=20), due to damage to the anterior cruciate ligament, its repair with additional augmentation was performed; in group 2 (n=20), anterior cruciate ligament reconstruction using tendon of the semitendinosus muscle was performed. Proprioceptive function was tested no earlier than 12 months after surgery using the method of active reproduction of passive positioning and the force sense reproduction method. In addition, the functional state of the treated knee joint was compared using the Knee and Osteoarthritis Outcome Score and International Knee Documentation Committee questionnaire scales. The significance of differences between the study groups was assessed using the Mann-Whitney U-test (differences were considered statistically significant at p ≤ 0.05). Results and discussions. Despite the similar functional outcomes on the questionnaire scales (p&gt;0.05), the patients of group 1 achieved statistically significant better results of the proprioception coefficient for all the methods used in comparison with group 2 (p&lt;0.05). In addition, a comparative assessment of the treated and contralateral healthy joint within the groups showed similar data in group 1 patients (p&gt;0.05) and statistically significant differences in group 2 (p&lt;0.05) also for all methods used. Conclusion. The study demonstrated that the proprioception of the knee joint after anterior cruciate ligament repair is almost identical to that in the contralateral healthy joint and is significantly better than after anterior cruciate ligament reconstruction with a semitendinosus muscle tendon.

Imposing Healthy Hip Motion Pattern and Range by Exoskeleton Control for Individualized Assistance

Powered exoskeletons are promising devices to improve the walking patterns of people with neurological impairments. Providing personalized external assistance though is challenging due to uncertainties and the time-varying nature of human-robot interaction. Recently, human-in-the-loop (HIL) optimization has been investigated for providing assistance to minimize energetic expenditure, usually quantified by metabolic cost. However, this full-body global effect evaluation may not directly reflect the local functions of the targeted joint(s). This makes it difficult to assess the direct effect when robotic assistance is provided. In addition, the HIL optimization method usually does not take into account local joint trajectories, a consideration that is important in imposing healthy joint movements and gait patterns for individuals with lower limb motor deficits. In this paper, we propose a model-free reinforcement learning (RL)-based control framework to achieve a normative range of motion and gait pattern of the hip joint during walking. Our RL-based control provides personalized assistance torque profile by heuristically manipulating three control parameters for hip flexion and extension, respectively, during walking. A least square policy iteration was devised to optimize a cost function associated with control efforts and hip joint trajectory errors by tuning the control parameters. To evaluate the performance of the design approach, a compression sleeve was used to constrain the hip joint of unimpaired human participants to simulate motor deficits. The proposed RL control successfully achieved the desired goal of enlarging the hip joint's range of motion in three participants walking on a treadmill.

Minimally Invasive Radiographic Evaluation of the Dysplastic Hip Joint Configuration in Terms of Surgical Treatment with Hip Preservation by PAO.

Residual developmental dysplasia of hip (RDDH) is a factor of early osteoarthritis of the hip. The main problems are pain and instability of the hip joint due to inadequate coverage of the femoral head by the acetabulum. The purpose of this study was to radiologically evaluate RDDH after Bernese periacetabular osteotomy (PAO) and to compare RDDH to healthy hips. The radiological parameters of RDDH treated by PAO were retrospectively evaluated. Digital AP pelvic radiographs were taken, including parameters of central edge angle and femoral head coverage, medialization, distalization, and ilio-ischial angle. Clinical assessment is based on the VAS scale. The study group consisted of patients with RDDH, and the control group consisted of patients without RDDH. After PAO radiological parameters decreased: medialization by 2.68mm, distalization by 3.65mm, and ilio-ischial angle by 2.62°. However, there was an increase in the parameters: CEA by 17.61° and FHC by 16.46%. There was a mean 3 point decrease in pain on the VAS scale. There was also a statistically significant radiological difference in the structure of dysplastic hip joints before surgery and healthy hip joints of the control group. Radiological studies confirmed the effectiveness of the PAO method in the treatment of RDDH. Based on all radiological parameters, differences between healthy and dysplastic hip joints were demonstrated. We believe that a thorough understanding of the values of radiological parameters used to describe dysplastic hip joints will allow us to improve the imaging diagnosis of this condition.

Unbiased comparison and modularization identify time-related transcriptomic reprogramming in exercised rat cartilage: Integrated data mining and experimental validation.

Exercise is indispensable for maintaining cartilage integrity in healthy joints and remains a recommendation for knee osteoarthritis. Although the effects of exercise on cartilage have been implied, the detailed mechanisms, such as the effect of exercise time which is important for exercise prescription, remain elusive. In this study, bioinformatic analyses, including unbiased comparisons and modularization, were performed on the transcriptomic data of rat cartilage to identify the time-related genes and signaling pathways. We found that exercise had a notable effect on cartilage transcriptome. Exercise prominently suppressed the genes related to cell division, hypertrophy, catabolism, inflammation, and immune response. The downregulated genes were more prominent and stable over time than the upregulated genes. Although exercise time did not prominently contribute to the effects of exercise, it was a factor related to a batch of cellular functions and signaling pathways, such as extracellular matrix (ECM) homeostasis and cellular response to growth factors and stress. Two clusters of genes, including early and late response genes, were identified according to the expression pattern over time. ECM organization, BMP signaling, and PI3K-Akt signaling were early responsive in the exercise duration. Moreover, time-related signaling pathways, such as inositol phosphate metabolism, nicotinate/nicotinamide metabolism, cell cycle, and Fc epsilon RI signaling pathway, were identified by unbiased mapping and polarization of the highly time-correlated genes. Immunohistochemistry staining showed that Egfr was a late response gene that increased on day 15 of exercise. This study elucidated time-related transcriptomic reprogramming induced by exercise in cartilage, advancing the understanding of cartilage homeostasis.

Extracellular Vesicle-Mediated miR-150-3p Delivery in Joint Homeostasis: A Potential Treatment for Osteoarthritis?

Background: The disruption of joint homeostasis is a critical event during the process of joint injury in osteoarthritis (OA). As regulatory molecules, microRNAs (miRNAs) can be released from secretory cells and delivered to recipient cells through extracellular vesicles (EVs), thereby playing an important role in regulating joint homeostasis. We hypothesized that the fibroblast-like synoviocytes (FLSs) in healthy joints could release EVs enriched in miRNAs that can maintain joint homeostasis by regulating the signal transduction pathways in the joints, whereby the articular cartilage (AC) is protected from degeneration, and OA progression is delayed. Methods: Via high-throughput sequencing and qPCR, we found that miR-150-3p was enriched in the circulating EVs in healthy rats. Next, we established an in vitro cell model in which chondrocytes were cultured with (i) FLSs transfected with miR-150-3p mimics or (ii) EVs released by FLSs (FLS–EVs) inside the healthy synovial membrane (SM). The transportation mechanism from FLSs to chondrocytes was studied using the EV inhibitor GW4869, and the FLSs were transfected with a miR-150-3p mimic or inhibitor. To assess the therapeutic effect of miR-150-3p-carrying EVs (EVs-150) in vivo, healthy FLS-derived EVs (H-FLS–EVs) were injected into the tail vein of rats with OA at various stages of the pathogenesis and evaluated for the progression of OA. Results: The chondrocytes could uptake fluorescent-labeled miR-150-3p mimics and FLS–EVs, and GW4869 suppressed this uptake. The overexpression of miR-150-3p could significantly reduce the concentrations of pro-inflammatory cytokines in the cell culture medium and the expression of the miR-150-3p target T cell receptor-interacting molecule 14 (Trim14), as well as the innate immune-related factors, including nuclear factor kappa B (NF-κB) and interferon-β (IFN-β). Similarly to the in vitro findings, the miR-150-3p level in the serum EVs was significantly upregulated among the EV-treated rats. In the AC of the OA rat model injected with H-FLS–EVs, the joint degeneration was suppressed, and Type II collagen (COLII) and aggrecan (ACAN) were significantly upregulated, whereas the innate immune-related factors Trim14, NF-κB, and IFN-β were downregulated compared with the levels in the untreated OA rats. Notably, the suppression of joint degeneration was more significant when H-FLS–EVs were administered at the early stages of OA rather than the late stages. Conclusion: H-FLS–EVs protect chondrocyte function and maintain joint homeostasis by modulating the innate immune response by suppressing the Trim14/NF-κB/IFNβ axis. These effects are achieved through the EV-mediated transport of miR-150-3p from the FLSs to the chondrocytes. Our findings show that EV-mediated miR-150-3p can be used to suppress OA, thus providing a novel therapeutic strategy. Additionally, the EV-mediated miR-150-3p transport may also serve as a potential biomarker in the diagnosis, treatment, and prognosis of OA.

Temporomandibular Joint Conditions in Patients with Craniofacial Microsomia (Literature Review)

Syndromes of I and II gill arches called maxillofacial dysostoses are accompanied by damage of temporomandibular joint (TMJ). Craniofacial microsomia is one of the of maxillofacial dysostoses. This syndrome has a number of features associated with clinical manifestations which should be taken into account at steps of the diagnosis and treatment of such patients. The degree of mandibular hypoplasia in this pathology can vary from 0 to 3, and it is inversely proportional to the integrity of the articular disc on the side of the lesion. An increased mechanical load on a healthy joint leads to its dysfunction and dislocation of the articular disc at the healthy side. In addition to hypoplasia of bone structures, craniofacial microsomia is accompanied by subatrophy of masticatory muscles and that in couple leads to malocclusion and myodynamic imbalance. Before drawing up a treatment plan it is necessary to study the state of the TMJ on both sides using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). The approach to treatment should be individual, combined, staged, based on the severity of the symptom complex.

The effect of mandibular movement on temporomandibular joint morphology while eating French fries

BackgroundThe preferred masticatory side was reported to be almost always the same as the affected side of the temporomandibular disorder. Unbalanced alterations of temporomandibular joint morphology were found to be associated with unilaterally masticatory habits. The aim of this study was to investigate the effect of the mandibular movement on the remodeling of temporomandibular joint during eating French fries using a 3D motion capture system. MethodsTwelve volunteers with non-maxillofacial deformity and a healthy temporomandibular joint were recruited. The 3D models of the mandible and the maxilla were reconstructed according to computed tomography. The subjects were asked to eat French fries by unilaterally mastication, which was recorded by a 3D motion capture system. The trajectories of the incisors and the condyles and the condylar acceleration during unilateral mastication were analyzed. ResultsDuring incisal biting, there was no significant difference in the condylar trajectories between the left and right sides (P > 0.05). During unilateral mastication, the average displacement and acceleration of the masticatory condyles were significantly lower than those of the non-masticatory condyles (P < 0.05). The trajectory angles of the masticatory condyles were significantly steeper than those of the non-masticatory condyle (P < 0.05). During swallowing, there was no obvious movement of the mandible. ConclusionsBetween both temporomandibular joints, unilateral mastication resulted in significant differences in the regions of the condylar movement within the articular fossa, and then caused different compressive regions of the temporomandibular joints. Thus, unilateral mastication might result in a significantly different pattern of temporomandibular joint remodeling between the two sides.

The expression of nerve growth factor in healthy and inflamed equine chondrocytes analysed by capillary western immunoassay

Nerve Growth Factor (NGF) is a signalling molecule for pain and inflammation. NGF is increased in synovial fluid from osteoarthritic humans and animals, compared to healthy controls. Monoclonal antibody therapy directed against NGF has been approved to treat pain in osteoarthritic dogs but despite many years of trialling, therapy has not been approved for human use. One reason for this is that adverse reactions with rapidly progressing osteoarthritis has occurred in some individuals. More detailed knowledge of NGF expression in joints is needed. In this study, capillary-based Simple Western was used to analyse NGF in cultured equine chondrocytes. Chondrocytes were collected post mortem from three macroscopically healthy intercarpal joints and three intercarpal joints with mild osteoarthritic changes. The chondrocytes were expanded to passage one and seeded in chondrogenic medium to maintain the phenotype. On day four, cells were either stimulated with LPS or kept untreated in medium. All cells were harvested on day five. Wes analysis of lysates did not show mature NGF but two proforms, 40 and 45 kDa, were identified. Results were confirmed with western blot. The same proforms were expressed in chondrocytes from healthy and osteoarthritic joints. Acute inflammation induced by LPS stimulation did not change the forms of expressed NGF. Capillary Simple Western offers a sensitive and sample-sparing alternative to traditional western blot. However, confirmation of peaks is imperative in order to avoid misinterpretation of findings. In addition, in this case the method did not offer the possibility of quantification advertised by the manufacturers.

Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis.

Osteoarthritis (OA) is a major cause of equine lameness. Cannabinoid (CB) receptors are now considered to be promising therapeutic targets in human rheumatology for pain and inflammation, however, little is known about the equine endocannabinoid system. The primary goal was to assess the presence and expression pattern of CB1 and CB2 in the synovium of healthy joints. A secondary goal was to explore the relationship between the CB expression, degree of synovitis and OA pathology. Ex vivo experimental study. Metacarpophalangeal joints (n=25) from a tissue bank were studied. The joints were dissected, and the articular cartilage lesions were scored. Synovial membrane specimens (n=45) were harvested, fixed and the degree of synovitis was graded on histological sections. Colocalised synovial sections were also immunostained with antibodies to CB1 and CB2. Five regions of interest were randomly selected from digital images of manually segmented synovial intima and scored blindly for positive cellular immunoreactive staining by two independent observers. Interobserver agreement was calculated with an intraclass correlation coefficient (ICC). Relationships between CB1 and CB2 immunoreactive scores and synovitis or joint OA grade were explored with mixed linear models. CB1 was expressed in synovial intimal cells in all specimens studied whereas CB2 expression was identified in 94%. Both receptors were also expressed in the subintimal blood vessel walls. ICCs were 84.6% (CB1) and 92.9% (CB2) for the immunoreactivity scores. Both CB1 and CB2 expression were significantly upregulated (p=0.04 and p=0.03, respectively) with increasing degree of synovitis. Conversely, CB1 expression significantly decreased (p=0.03) with increasing severity of OA. The type of synovial cell expressing CB1 or CB2 was not investigated. Equine synovial intimal cells constitutively express both CB1 and CB2 receptors that are upregulated with synovitis and may have a role in joint pain. They are potential targets for therapy with cannabinoid molecules or their derivatives.

A Training Method for a Sensor-Based Exercise Rehabilitation Robot

In order to solve the problem that the traditional mirror therapy did not take into account the real-time recovery of the affected limb and the training effect was limited, a training method of sports rehabilitation robot based on sensor was proposed. A mirror active rehabilitation training system was proposed, which was composed of four steps including trajectory acquisition of the limb inertial measurement unit (IMU), fuzzy adaptive proportion differentiation (PD) control in closed-loop variable domain, muscle force estimation of the surface electromyographic signal (sEMG) of the affected limb, and power compensation of the outer ring of the affected limb. The experimental results showed that the sagittal forward flexion angle of the healthy shoulder increased from 0° to 128° at a relatively uniform speed, and the sagittal forward flexion angle of the shoulder was basically consistent with that of the healthy limb after the adaptive power compensation of the affected limb. The calculated trajectory tracking error of the healthy limb controlled by the fuzzy adaptive PD controller in the variable domain was 0.21 ± 1.35 ° . The horizontal backward extension angle of the healthy shoulder joint increased from 0° to 43°, and the following trajectory of the affected limb was roughly consistent with the movement trajectory of the healthy limb. The calculated tracking error of the healthy limb trajectory was 0.39 ± 1.45 ° . It was concluded that the control system could provide the real-time power compensation according to the recovery of the affected limb, give full play to the training initiative of the affected limb, and make the affected limb achieve a better rehabilitation training effect.