Articular Cartilage Thickness Research Articles

Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets

Abstract Type 2 diabetes mellitus (T2DM) is a significant risk factor for osteoarthritis (OA), and metformin, as the main therapeutic drug for T2DM, has shown positive effects on OA without a clear mechanism. This study aimed to explore the protective effects and mechanisms of oral metformin in T2DM-induced OA. We identified differentially expressed genes, using the GSE117999 and GSE98918 datasets, and protein–protein interaction networks were analyzed using the MCODE algorithm in cytospace to finalize the OA hub genes (S100A8, S100A9, and S100A12). To validate whether S100A8, S100A9, and S100A12 are potential targets of action for OA, we randomly divided 40 SD rats into a control group (CG, n = 10) and a T2DM group (n = 30). We modeled rats in the T2DM group with streptozotocin (35 mg/kg, i.p.) and a high carbohydrate and fat diet. Finally, 20 were randomly selected and divided into the T2DM group (n = 10) and the treated group (Met + T2DM, n = 10), and the treated group was given Met (180 mg/kg/day) by gavage for 8 weeks. We subsequently used histological assessment to show that oral metformin mitigated the development of T2DM-associated OA as indicated by the OA Research Society International score and articular cartilage thickness, and immunohistochemistry also confirmed that metformin significantly reduced the expression of S100A8, S100A9, and S100A12 in the knee joints of OA rats. In conclusion, metformin demonstrated a protective effect against OA in T2DM-induced rats, slowing knee OA progression by inhibiting S100A8, S100A9, and S100A12 expression. These findings suggest potential biological targets for future OA treatments.

Efficacy of adipose—derived stromal vascular fraction in treatment of osteoarthritis: an experimental study

BackgroundOsteoarthritis OA is a common progressive disabling disease. Current research aims at finding therapies to prevent its progression. In this work, we assessed the therapeutic role of intra-articular injection of stromal vascular fraction SVF in collagenase induced knee OA in rats.ResultsPost right Knee OA induction in 42 Wistar rats, histopathological examination and quantification of articular cartilage degeneration using Mankin’s score revealed degenerative changes were significantly higher in untreated Group II compared to SVF treated Group III at 1 month (10.75 ± 0.50 and 2.50 ± 0.53, P = 0.001) and 2 months (8.50 ± 0.58, 0.50 ± 0.53, P = 0.001), respectively. Morphometric computerized image analysis revealed a significant difference between treated, untreated and healthy control group I regarding chondrocyte cellular count, articular cartilage thickness and optical density OD of the cartilage (P < 0.001). Group II contained the least chondrocyte cellular count. Also, articular cartilage thickness at 2 months was significantly less in Group II compared to SVF treated group (P < 0.001). The OD in Safranin-stained slides, as an indicator of proteoglycan content of the matrix, was highest in Group I followed by Group III and lowest in Group II with a highly significant difference between untreated and treated groups at 1 month (67.32 ± 4.25, 81.77 ± 3.09, P = 0.000) and 2 months (71.60 ± 3.49, 83.26 ± 5.47, P = 0.000), respectively.ConclusionTreatment with adipose-derived SVF decreased the development of articular cartilage degenerative changes at early stages of induced OA in rats. Later, on follow-up, the preserved articular cartilage thickness, cellular count and increased proteoglycan content rendered SVF a promising regenerative therapy for Knee OA.

Microwave Ablation of the Pig Growth Plate: Proof of Concept for Minimally Invasive Epiphysiodesis.

Different surgical methods for epiphysiodesis of limb length discrepancy (LLD) have been described. Although these methods are variably effective, they are associated with morbidity (pain and limp) and potential complications. Microwave ablation is a less-invasive opportunity to halt growth by selectively destroying the growth plate via thermal energy to treat LLD in children. In this proof-of-concept study using an in vivo pig model, we asked: (1) What is the durability of response 2 to 4 months after microwave ablation of the tibial growth plate as measured by length and angulation of the tibia via a CT scan? (2) Was articular cartilage maintained as measured by standard histologic staining for articular cartilage viability? To develop an in vivo protocol for microwave ablation, we placed microwave antennas adjacent to the proximal tibia growth plate in the cadaveric hindlimbs of 18 3-month-old pigs. To determine the suitable time, we varied ablation from 90 to 270 seconds at 65-W power settings. After sectioning the tibia, we visually assessed for discoloration (implying growth plate destruction) that included the central growth plate but did not encroach into the epiphysis in a manner that could disrupt the articular surface. Using this information, we then performed microwave ablation on three live female pigs (3.5 to 4 months old) to evaluate physiologic changes and durability of response. A postprocedure MRI was performed to ensure the intervention led to spatial growth plate alterations similar to that seen in cadavers. This was followed by serial CT, which was used to assess the potential effect on local bone and growth until the animals were euthanized 2 to 4 months after the procedure. We analyzed LLD, angular deformity, and bony deformity using CT scans of both tibias. The visibility of articular cartilage was compared with that of the contralateral tibia via standard histologic staining, and growth rates of the proximal tibial growth plate were compared via fluorochrome labeling. Eighteen cadaveric specimens showed ablation zones across the growth plate without visual damage to the articular surface. The three live pigs did not exhibit changes in gait or require notable pain medication after the procedure. Each animal demonstrated growth plate destruction, expected limb shortening (0.8, 1.2, and 1.5 cm), and bony cavitation around the growth plate. Slight valgus bone angulation (4º, 5º, and 12º) compared with the control tibia was noted. No qualitatively observable articular cartilage damage was encountered from the histologic comparison with the contralateral tibia for articular cartilage thickness and cellular morphology. A microwave antenna placed into a pig's proximal tibia growth plate can slow the growth of the tibia without apparent pain and alteration of gait and function. Further investigation and refinement of our animal model is ongoing and includes shorter ablation times and comparison of dynamic ablation (moving the antennae during the ablation) as well as static ablation of the tibia from a medial and lateral portal. These refinements and planned comparison with standard mechanical growth arrest in our pig model may lead to a similar approach to ablate growth plates in children with LLD.

Effect of functional knee loading on articular cartilage MRI T2 relaxation time and thickness in patients at risk for knee osteoarthritis

ObjectivesThe objectives of this study were: 1) to evaluate the effect of a functional loading stimulus on MRI-acquired T2 relaxation time (T2) and thickness of knee articular cartilage, and 2) to compare the response between patients at risk for knee OA and healthy controls. DesignA total of 32 participants (16 healthy controls [24.7 ± 3.0 years], and 16 at-risk participants [37.5 ± 12.2]) underwent 3T MRI T2 mapping scans immediately before and after a standardized 25-minute functional loading stimulus on a computerized treadmill that included a variety of challenging walking conditions. Groups were defined using the Osteoarthritis Initiative Control (healthy) and Incidence Cohort (at-risk) Criteria. We analyzed changes in T2 between groups in the superficial and deep layers of tibiofemoral, patellar, and trochlear cartilage, and for tibiofemoral cartilage thickness using multivariate linear mixed-effects models. ResultsT2 was shorter in the superficial cartilage layers in both groups. The mean combined change (95 % confidence interval) in T2 of the superficial layer was -3.80 ms (-4.87; -2.73) for at-risk participants and -3.89 ms (-4.96; -2.82) for healthy controls. The between-group difference in change was 0.09 ms (-1.04; 1.22). There was a decrease in articular cartilage thickness in the lateral compartment for healthy controls (-0.14 mm [-0.24; -0.04]), otherwise there were no changes detected. ConclusionsConsistently shorter T2 was observed in the articular cartilage of patients at risk for knee OA and in healthy controls, after a challenging walking test, but with no concurrent change in cartilage thickness, suggesting a similar articular cartilage response to functional loading.

Ultrasound Measurement of Femoral Articular Cartilage Thickness Before and After Marathon Running.

The purpose of this study was to use ultrasonography to measure femoral articular cartilage thickness changes during marathon running, which could support MRI studies showing that deformation of knee cartilage during long-distance running is no greater than that for other weight-bearing activities. Participants included 38 marathon runners with no knee pain or history of knee injury, aged 18-39. Ultrasound images of the femoral articular cartilage were taken two hours before and immediately after the race. Femoral articular cartilage thickness was measured at both the medial and lateral femoral condyles. The maximum change in femoral articular cartilage thickness, measured at the left outer lateral femoral condyle, was 6.94% (P=.006). All other femoral articular cartilage thickness changes were not significant. A change in femoral articular cartilage thickness of 6.94% supports our hypothesis that long-distance running does not induce deformational changes greater than that of regular daily activities. This study using ultrasonography supports MRI evidence that knee cartilage tolerates marathon running well.

Ameliorative Effect of Vitamin D on Articular Cartilage Thickness in Arthritic Rat Model

Objective: To determine the protective effect of vitamin D on the articular cartilage of formalin-induced arthritis in rats.Study Design: Lab–based Experimental study.Place and Duration of Study: The study was carried out at the Department of Anatomy, Islamic International Medical College from September 2020 to September 2021.Methods: We randomly split thirty adult male albino rats weighing between 250 and 300 grams into three groups. (10 in total). On days 1 and 3 of the experiment, formaldehyde was subcutaneously injected into the right paw of every animal, with the exception of those in group A. The usual rat food was given to the rats in Groups A and B. Throughout the trial, Rats in group C were given vitamin D 4000IU/kg orally by adding cholecalciferol (Vitamin D3) injection in a standard diet for 28 days. All of the animals were dissected after the experiment, and the right hind leg was taken out, processed, and stained with H&amp;E for a microscopic assessment of the thickness of the unclarified cartilage. Version 21 of SPSS was used to analyze the results.Results: The oral administration of vitamin D exhibited a significant increase in unclarified cartilage thickness on intergroup comparison.Conclusion: Vitamin D is an effective antiarthritic agent in ameliorating the thickness of articular cartilage thickness in arthritic rat models.&#x0D; How to cite this: Shahid A, Beenish H, Khurshid T, Rashid A, Shahid U, Khan M. Ameliorative Effect of Vitamin D on Articular Cartilage Thickness in Arthritic Rat Model. Life and Science. 2024; 5(1): 107-112. doi: http://doi.org/10.37185/LnS.1.1.570

The effect of attending rehabilitation after traumatic knee joint injury on femoral articular cartilage morphology in collegiate rugby players with a history of intracapsular knee joint injury during two-year consecutive rugby seasons.

This present study aimed to compare ultrasonographic measures of femoral articular cartilage during two-year seasons between collegiate rugby players who have attended supervised rehabilitation following intracapsular knee joint injury and those without a history of knee injury. Using a prospective observational study design, 12 male collegiate rugby players with a previous history of intracapsular knee joint injury who have received and completed supervised rehabilitation following their injury and 44 players without knee joint injury participated in this study. Ultrasonographic images were used to verify changes in femoral articular cartilage thickness and cross-sectional area (CSA) with or without a previous history of knee joint injury over two consecutive rugby seasons. Significant time main effects were observed for the lateral condylar thickness (p < 0.001), the intercondylar thickness (p = 0.001), the medial condylar thickness (p < 0.001), and CSA (p < 0.001). No significant interactions nor group main effects were identified for all femoral articular cartilage (p < 0.05). Collegiate rugby players demonstrated a decrease in femoral articular cartilage thickness and CSA over two-year consecutive rugby seasons. These findings indicate that engaging in collegiate rugby induces alterations in femoral articular cartilage structure. Furthermore, there were no differences in all femoral cartilage outcome measures between rugby players with and without a previous history of traumatic knee joint injury. Therefore, attending supervised rehabilitation at the time of their knee joint injury appeared to reduce the impact of a previous history of intracapsular knee joint injury on the change in femoral articular cartilage thickness and CSA among active rugby players.

Ex Vivo Comparison of the Diagnostic Performance of Two-Dimensional and Three-Dimensional Three-Tesla Magnetic Resonance Imaging Sequences in Depicting Normal Articular Cartilage in Equine Stifle Cadavers.

The objective of this study was to compare articular cartilage thickness observed in the different 2D and 3D sequences to the cartilage thickness of the equine stifle in cadavers to determine the accuracy of each sequence. The study was conducted as a blinded laboratory study using seven equine stifle specimens. The 2D (T2W TSE) and 3D (3D VIEW T2W HR, T2 3D mFFE, T1W VISTA SPAIR, 3D PDW SPAIR) 3-tesla MRI sequences of each stifle were obtained. Cartilage thickness was measured at 30 locations on MRI and on gross pathology. Thickness measurements were compared using a Bland-Altman plot and post hoc analysis tests. The 3D sequences were found to be generally more accurate than the 2D sequence (p < 0.001). The smallest difference to macroscopic measurements was observed in the 3D VIEW T2W HR and T1W VISTA SPAIR sequences with no statistical difference between each other. Knowing the accuracy of different sequences will improve the evaluation of equine cartilage and the early detection of cartilage pathologies. This would promote MRI as a noninvasive imaging modality for horses suffering from stifle lameness with no findings in conventional imaging methods. Furthermore, since 3D sequences seem to have better accuracy in depicting cartilage, they may replace 2D sequences, thereby shortening scanning times.

Association of Knee Osteoarthritis and Flexion Contracture With Localized Tibial Articular Cartilage Loss: Data From the Osteoarthritis Initiative.

To evaluate whether a knee flexion contracture (FC) was associated with localized tibial articular cartilage loss over a 1-year period using Osteoarthritis Initiative quantitative data. Five hundred seventy-eight participants from a previously established nested case-control study of people with radiographic knee OA with or without progression, based on radiographs and symptoms, had their knee range of extension measured at baseline and received magnetic resonance imaging (MRI) at baseline and 1 year. The tibial articular cartilage of the medial and lateral condyles was segmented into anterior, center, and posterior regions. We tested for associations between knee FC (defined as lack of extension to 0°), and localized changes in tibial articular cartilage thickness or percent of denuded bone (0 mm thickness) after 1 year relative to baseline using ANOVA, controlling for baseline MRI outcomes and clinical factors. Knee FC was associated with denuded bone in the medial condyle center (β 0.44, 95% CI 0.02-0.86) and preserved cartilage thickness in the medial condyle posterior (β 0.01, 95% CI 0.002-0.03) regions. Knee FC unloading the tibial center region and loading the posterior region was associated with localized articular cartilage loss centrally and preserved articular cartilage posteriorly. These findings are consistent with knee FC negatively affecting unloaded tibial articular cartilage.

Effects of extracorporeal shockwave therapy for mild knee osteoarthritis: A pilot study.

Extracorporeal shockwave therapy (ESWT) has been widely used for various musculoskeletal disorders, including knee osteoarthritis (OA), and has been shown in several studies to be a safe treatment. Although some studies have confirmed the pain-relieving effect of ESWT for knee OA, research on objectivity for structural changes in knee OA is lacking. The aim of this study was to evaluate the ESWT treatment mechanisms in patients with knee OA by means of clinical symptoms and ultrasound techniques as objective measures. Eighteen patients with mild knee OA were enrolled and randomized to 1 of 2 treatment groups: active or sham. Patients in the experimental group received 0.05 mJ/mm² total energy with 1000 pulses weekly for 3 weeks. We then assessed them before, immediately after, and 1-month after the last treatment using the following measurements: pain on a visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne index, knee joint range of motion, and ultrasonographic features (articular cartilage thickness, Doppler activity, and joint effusion height). All 18 patients completed the 3 treatment sessions without any complication. Both the experimental and control groups improved in terms of OA symptoms, as measured by the visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index score, and Lequesne index (P < .05). The height of the suprapatellar effusion decreased with time course in the experimental group (P < .05) and showed significant differences with control group at 1-month follow-up (P < .05). The experimental group showed an increase in knee flexion range of motion and Doppler activity immediately following the last treatment session (P < .05), but the effect was not sustained at the 1-month follow-up. Although the therapeutic activity itself could improve OA symptoms, objective improvements were only observed after ESWT. Suprapatellar effusion height was reduced after ESWT and the effect was maintained after 1-month. Our results suggest that ESWT may be effective in reducing suprapatellar effusion and improving symptoms in mild knee OA. However, studies with a larger sample size are required.

MRI overestimates articular cartilage thickness and volume compared to synchrotron radiation phase-contrast imaging.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.

Mathematical Model to Study the Squeeze Film Characteristics of Diseased Human Synovial Knee Joint

Synovial fluid functions as a biological lubricant and lubricates articular cartilage to reduce friction and wear. Lubricin and hyaluronic acid are the primary components of synovial fluid responsible for its lubricating properties. The loss of properties in synovial fluid and articular cartilage due to aging and activities can restrict mobility in synovial joints, resulting in the degradation of articular cartilage and ultimately leading to pathological synovial joints, which is a major cause of disability. Thus, research on synovial joints remains crucial, and despite previous investigations on synovial joint lubrication, there are several issues related to squeeze film lubrication that require further attention. The Newtonian model of squeeze film lubrication in synovial joints needs to be extensively studied. In this study, lubrication and other related properties of synovial fluid are studied theoretically. In this paper, we have studied the flow of synovial fluid in the diseased synovial joint. Further, we have studied the effect of the viscosity of the synovial fluid, the permeability of articular cartilage, thickness of articular cartilage, and fluid film thickness on the characteristic of the squeeze film formed between the articular cartilages of the diseased human knee joint. The flow of synovial fluid is modeled by considering it as a viscous, incompressible and Newtonian fluid. We have derived the modified Reynolds equation using the principle of hydrodynamic lubrication and continuum mechanics theory and solved it by applying the suitable boundary conditions according to the physical considerations. Subsequently, we obtained the expression for pressure distribution in fluid film, load-bearing capacity, and squeeze time and have done the theoretical analysis on these properties for different parameters. Pressure increases with squeeze velocity and viscosity of the synovial fluid and decreases with permeability and fluid film thickness. Human knee joint becomes diseased due to excessive pressure, and the mobility of the knee joint decreases. The load capacity increases with viscosity and squeeze velocity and decreases with permeability resulting in the reduction of the load-carrying capacity of the knee joint in diseased conditions. Moreover, the squeeze time also increased in the diseased state of the joint.

Adipose-Derived Stromal Vascular Fraction in Treatment of Osteoarthritis: Experimental Study

Background Osteoarthritis OA is the commonest musculoskeletal disabling disease in adults. Most of the current available treatments provide only symptomatic relief. Adipose derivedstromal vascular fraction SVF has been recently introduced as potential regenerative therapy for OA. Objective We aimed to study the therapeutic role of adipose – derived SVF in OA. Materials and Methods This work included 42 female Wister rats for induction of osteoarthritis and 6 male Wistar rats acting as donors for the extraction of SVF from adipose tissue which yielded 106 cells/ml. Osteoarthritis was induced by intra-articular injection of collagenase type II in the right knee joint of all female rats and the left knee was considered as healthy controls. Rats were divided into three groups, healthy control Group (group I), induced osteoarthritis control group (Group II) which received no treatment and SVF treatment group (Group III). Group II and III were subdivided into 2 subgroups; IIa, IIb and IIIa, IIIb which were euthanized after 1 and 2 months of OA induction respectively. Modified Manikin score (MS) was used to assess cartilage degeneration. Image Analysis was used to assess chondrocyte count, articular cartilage thickness and optical density in slides stained with Hematoxylin and Eosin and Safranin-O-stain. Results It was observed that MS scored highest in Group II compared to Group III and Group I (P &amp;lt; 0.001). After 1 month, MS in Group IIa and Group IIIa was (10.75 ± 0.50 and 2.50 ± 0.53, P &amp;lt; 0.001). Similarly at 2 months MS was (8.50 ± 0.58, 0.50 ± 0.53, P &amp;lt; 0.001). Also, morphometric analysis revealed Group II contained least chondrocyte cellular count compared to Group III and Group I (P &amp;lt; 0.001). After 2 months, articular cartilage thickness was least in Group II compared to Group IIIb and highest in Group I (P &amp;lt; 0.001). Also, optical density OD measurement using imaging in slides stained with Safranin revealed OD was highest in Group I, followed by Group III and least in Group II (P &amp;lt; 0.001). Conclusion Adipose derived SVF represents potential regenerative therapy for OA. It decreased development of degenerative changes at early stages of induced osteoarthritis in rats and promoted regeneration with increased cartilage thickness and proteoglycan content at later stage.

Ameliorative Effects of Prolotherapy on Histomorphology of Tibial Articular Cartilage of Chemically Induced Osteoarthritic Knee Joint in a Rat Model.

To determine the ameliorative effects of prolotherapy on monosodium iodoacetate (MIA) induced and histomorphological changes in the articular cartilage of tibial condyles at rat knee joint. An experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College Rawalpindi, NUMS, Rawalpindi, from August to November 2021. Thirty adult male Sprague Dawley rats were divided into three groups, each having 10 rats. Group A was control. Group B was injected with single dose of 1mg MIA intraarticularly in the right knee to induce osteoarthritic changes. Group C was injected with single dose of 1mg MIA intraarticularly, in right knee was followed by 0.1ml Prolotherapy (3ml of 25% dextrose, 2ml of 2% xylocaine, 1ml of injection neurobion, and 1ml of injection methecobal) as intra articular injection at week 2, 6 and 10 in right knee. Rats were sacrificed after one month of the last dose of Prolotherapy. Articular cartilage was collected for gross and histological examination and compared among the groups. Articular cartilage belonging to control group A was normal. While group B showed statistically significant deterioration in gross appearance (p = 0.001**), reduction in number of chondrocytes (p = 0.005*) and thickness of articular cartilage (p = 0.001**) in comparison to group A. In group C due to prolotherapy statistically significant improvement in gross appearance (p = 0.034*), increase in number of chondrocytes (p = 0.003*), and thickness of articular cartilage (p = 0.001**) was observed as compared to group B. Prolotherapy significantly ameliorates histomorphology of tibial articular cartilage against MIA induced osteoarthritic changes in rat knee joint. Articular cartilage, Knee joint, Monosodium iodoacetate, Osteoarthritis, Prolotherapy.

Lateral meniscus with tears or with histologic calcification does not increase the risk of lateral osteoarthritis after medial unicompartmental arthroplasty.

Meniscal tears or histological meniscal calcifications (in the absence of radiological chondrocalcinosis) are frequent in osteoarthritis. Whether lateral meniscal lesions influence clinical outcomes after medial unicompartmental knee arthroplasty (UKA) is unknown. We analyzed 130 patients (130 knees) with medial unicompartmental knee arthroplasties between 2005 and 2015. These 130 knees had full articular cartilage thickness in the lateral compartment and no radiological chondrocalcinosis on preoperative radiographs. The lateral meniscus was analyzed with preoperative MRI and a biopsy of the anterior horn at the time of surgery. Synovial fluid was collected and analyzed for calcium pyrophosphate dihydrate crystal deposition (CPPD crystals). Lateral meniscal tears were untreated when detected on MRI or during surgery, with the hypothesis that these tears on the opposite compartment would remain asymptomatic in medial UKA. At average 10-year follow-up, patients were evaluated with clinical and radiographic outcome, with a focus on the risk of joint space narrowing of the lateral femorotibial compartment. CPPD crystals were present in the synovial fluid of 70 knees. Lateral meniscal tears were seen on MRI in 34 (49%) normal meniscuses of the 60 knees without CPPD crystals and in six other knees without histological meniscal calcification despite CPPD crystals. Histological calcification was present on 61 lateral meniscuses with 53 meniscal tears. The results showed no significant differences in the clinical outcomes between knees with lateral meniscal tears or lateral meniscal histological chondrocalcinosis or both lesions and those without these conditions. Additionally, radiographic progression of osteoarthritis in the opposite femorotibial compartment of the knee was not more frequent in patients with these meniscal issues. The tenyear cumulative survival rates, measured by the need for total knee arthroplasty, were 91% for knees without meniscal lesions and 92% for knees with these lesions. On this basis, treatment of meniscal tears of the lateral compartment and routine aspiration of the knee to assess for birefringent crystals in the planning of medial UKA do not appear necessary.

Anabolic phenotype in cartilage-specific mitogen-inducible gene-6 knockout mice is independent of transforming growth factor-α

Background/objectiveOsteoarthritis (OA) is a whole joint disorder with no disease modifying treatment currently available. The Epidermal Growth Factor Receptor (EGFR) signaling pathway plays an important role in cartilage/bone development and its ligand transforming growth factor-α (TGFα) is upregulated in OA. In contrast, Mitogen-inducible gene 6 (Mig6) is a negative regulator of EGFR, and cartilage-specific Mig-6 deletion results in anabolic effects on cartilage and formation of chondro-osseus nodules (CON). We aimed to attenuate EGFR signaling by inhibiting TGFα production in cartilage-specific Mig6 deficient mice, to test whether this would prevent the formation of CONs. MethodsWe generated double knockout mice by crossing cartilage-specific Mig-6fl/flCol2a1-Cre+/− and whole-body Tgfa± mice to generate experimental and control wild-type mice. Knee and elbow sections were used to examine articular cartilage thickness, cell density, and osteoclast presence. Additionally, immunohistochemistry was completed to analyze phospho-EGFR and SOX9. ResultsMig-6 deficient mice display cartilage thickening and CONs at 12 weeks in both the elbow and knee joints, which is independent of TGFα ligand presence. Similarly, articular cartilage cell density is increased in Mig6-cKO/Tgfa-KO and Mig6-cKOmice, but not Tgfa-KO mice, and displays increased SOX9 and phospho-EGFR staining. ConclusionThe articular cartilage displays increased thickness/cell density and CON formation independent of the presence of TGFα, suggesting the anabolic phenotype in the Mig6-deficient mice is independent of TGFα/EGFR binding. The anabolic phenotype may be due to an alternative EGFR ligand activation, or other non-EGFR specific mechanism. More research is required to elucidate the exact pathway responsible for the anabolic effects.

Protective effect of vaginal resveratrol administration on joint tissues in ovariectomized rats: Targeting mTOR and сaspase 3

IntroductionEstrogens play a considerable role in maintaining bone and articular cartilage homeostasis. Menopause provokes joint disorders due to metabolic syndrome and altered signaling pathways. Phytoestrogen resveratrol was demonstrated to provide chondroprotective and osteoprotective effects. However, the mechanisms of such action of Resveratrol are still being explored. AimThe study aims to determine the effect of Resveratrol on the joints and its therapeutic mechanism in ovariectomized rats. Material and methodsThe study was carried out on Wistar female rats that were divided into three groups, including control animals; ovariectomized rats (OVX); and the OVX group treated with an intravaginal gel containing Resveratrol (0.5 % 0.1 mL, daily 28 days). Knee joint tissues (articular cartilage, subchondral plate, subchondral bone) were assessed by histomorphometry. The expression of mTOR, PTEN, Caspase 3 and BCL-2 in articular cartilage and subchondral bone were evaluated immunohistochemically. ResultsResveratrol treatment of OVX rats prevented weight gain by 17 % (P < 0.001), demonstrating the systemic effect on metabolic pathways. Although there were no statistically significant differences in the thickness of articular cartilage between groups, OVX rats possessed degenerative changes in chondrocytes, associated with the enhanced expression of mTOR (P < 0.001) and Casp-3 (P = 0.005). Resveratrol decreased mTOR (P = 0.007) and Casp-3 (P = 0.011) expression in chondrocytes, reducing degenerative changes. At the same time, resveratrol attenuated the deterioration of trabecular bone in OVX rats (P = 0.002). This effect was through the up-regulation of BCL-2 (P = 0.018) and down-regulation of Casp-3 expression (P < 0.001). ConclusionsIntravaginal administration of resveratrol provided systemic effects and ameliorated joint tissue structure and signaling in OVX rats through stimulation of BCL-2 and reduced Casp-3 expression.

The short-term effect of glucosamine-sulfate, nonanimal chondroitin-sulfate, and S-adenosylmethionine combination on ultrasonography findings, inflammation, pain, and functionality in patients with knee osteoarthritis: A pilot, double-blind, randomized, placebo-controlled clinical trial.

This study aimed to investigate the efficacy of glucosamine-sulfate (GS), nonanimal chondroitin-sulfate (naCS), and S-adenosylmethionine (SAMe) combination on ultrasound findings, inflammation, pain, and functionality in knee osteoarthritis. In the prospective, randomized, double-blind, placebo-controlled pilot study conducted between August 2019 and November 2019, 120 participants (28 males, 92 females; mean age: 66.4±7.9 years; range, 42.4 to 74.5 years) were randomized at a 1:1:1 ratio to the placebo group, the first experimental group (a combination of GS, naCS, and SAMe was administered to the experimental groups. The first experimental group received 375 mg of GS, 300 mg of naCS, and 100 mg of SAMe, whereas the second experimental group received 750 mg of GS, 600 mg of naCS, and 200 mg of SAMe). Laboratory (erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, interleukin [IL]-1β, IL-6, IL-17), clinical (Visual Analog Scale [VAS], short form health survey [SF-36], the Western Ontario and McMaster Universities Arthritis Index [WOMAC], and the Tegner Lysholm Knee Scoring Scale [TLKS]), and musculoskeletal ultrasound (MSUS) assessments were performed at baseline and after three and six months. A minor increase was observed in the second experimental group after six months using ultrasonography to evaluate articular cartilage thickness (p<0.05). The investigational product's superiority in reducing osteoarthritis ultrasonographic findings was not proven. A moderately negative association was found between cartilage thickness and VAS scores at baseline (ρ=-0.36, p<0.01), while the presence of massive osteophytes on MSUS showed a low to moderate association with all clinical outcomes. There was no difference in the delta changes between groups for the VAS, TLKS, WOMAC, and SF-36. The only serum inflammatory marker outside the reference range was IL-1β, but no significant changes were observed after six months. According to the results of our investigation, treatment for knee osteoarthritis should be evaluated using more objective outcomes. The most important conclusion of our study is that IP may result in a slight increase in articular cartilage thickness, which was associated with a decrease in pain intensity at baseline. Clarification of the potential influence of this combination on radiographic progression and laboratory markers of inflammation requires further exploration.

Investigation of the effect of plasma jet on regeneration of rabbit knee cartilage

Articular cartilage is a connective tissue biomechanically, so the absence of blood vessels, nerves, lymph flow and low metabolism causes its slow and delayed regeneration. Therefore, it is very important to use the correct treatment methods for cartilage healing. Рurpose of study: Investigating the effect of plasma jet on rabbit knee cartilage regeneration. The present research was conducted on 12 New Zealand white adult male rabbits weighing approximately 2.0-2.5 kg. In order to prepare the knee cartilage, its debridement was sanitized by chondrectomy with scraping method in all three treatment groups. After three weeks of treatment, the rabbits were euthanized and the amount of cartilage regeneration was recorded macroscopically and by recording images, and samples were fixed in 10% formalin for histopathology test. The commonly used in pathology laboratories staining method was chosen. Observation and measurement of articular cartilage thickness was done with eye graticule. And at the end, the obtained data were analyzed statistically. The results obtained in the present study indicated that the use of plasma jet method improves the cartilage tissue in such a way that by examining the histopathological sections, it was found that the articular cartilage in the plasma jet group caused the formation of fibrocartilage tissue in the place of injury. Plasma jet has a positive effect on rabbit cartilage regeneration.

Application of diffuse optical back reflection spectroscopy for determining articular cartilage thickness in a clinical setting.

Develop a spectroscopic method to assess cartilage thickness during the arthroscopic examination. Currently, arthroscopy assesses cartilage damage visually; outcomes are based on the surgeon's subjective experience. Light reflection spectroscopy is a promising method for measuring cartilage thickness based on the absorption of light by the subchondral bone. In the presented study, in vivo diffuse optical back reflection spectroscopic measurements were acquired by gently placing an optical fibre probe on different locations of the articular cartilage of 50 patients during complete knee replacement surgery. The optical fibre probe consists of two optical fibers with a diameter of 1mm to deliver the light and detect back-reflected light from the cartilage. Centre to centre distance between the source and the detectorfibers was 2.4mm. Actual thicknesses of the articular cartilage samples were measured under microscopy using histopathological staining. Using half of the samples in the patient data, a linear regression model was formed to estimate cartilage thicknesses from the spectroscopic measurements. The regression model was then used to predict the cartilage thickness in the second half of the data. The cartilage thickness was predicted with a mean error of 8.7% if the actual thickness was less than 2.5mm (R2 = 0.97). The outer diameter of the optical fibre probe was 3mm, which can fit into the arthroscopy channel and can be used to measure the cartilage thickness in real-time during the arthroscopic examination of the articular cartilage.