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Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.
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Many patients who cannot squat well in a neutral toe position can only squat in an excessively out-toeing position. This excessive out-toeing squat is thought to be caused by rotational problems of the lower extremities. In this study, we aimed to identify the cause for the inability to squat by measuring and comparing femoral and tibial torsion between an excessive out-toeing squat patient group and a control group representing the general population. Between 2008 and 2022, a patient group comprising 50 lower extremities with excessive out-toeing squats was established. A control group representing the general population was selected from patients aged 0 to 29 years, who underwent lower-extremity CT angiography between 2012 and 2022, using the Clinical Data Warehouse with exclusion criteria applied. A total of 94 lower extremities were included in the control group. The femoral torsional angle (FTA) and tibial torsional angle (TTA) of both groups were measured and compared using Student t test. Additionally, 30 each of those with the highest and lowest 30 FTA values were selected from the patient and control groups, and the TTA was compared between the high- and low-FTA groups using Student t test. The mean FTA was 0.34° (SD, 11.11°) in the patient group and 10.14° (SD, 11.85°) in the control group, with a mean difference of 9.8° and Pâ <â .001. The mean TTA was 27.95° (SD, 7.82°) in the patient group and 32.67 ° (SD, 7.58°) in the control group, with a mean difference of 4.72° (Pâ =â .001). The mean TTA was 34.3° (SD, 7.72°) in the high-FTA group and 28.17° (SD, 8.35°) in the low-FTA group, with a mean difference of 6.13° (Pâ =â .005). Patients with excessive out-toeing squat showed lower FTA and TTA values than the general population. Furthermore, although a correlation between FTA and TTA was not established through Pearson correlation analysis, a tendency was observed where a decrease in FTA was associated with a decrease in TTA. Based on these results, decreased FTA was demonstrated to be one of the major causes of excessive out-toeing squats.
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Fémur , Tibia , Humanos , Fémur/diagnóstico por imagen , Masculino , Femenino , Adulto , Adolescente , Adulto Joven , Tibia/diagnóstico por imagen , Niño , Preescolar , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Estudios de Casos y Controles , Lactante , Anomalía Torsional/diagnóstico por imagen , Anomalía Torsional/fisiopatología , Postura/fisiología , Anciano , Estudios RetrospectivosRESUMEN
In the original publication [...].
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Osteoarthritis is a significant global health problem. Many patients seek more effective alternatives to nonsteroidal anti-inflammatory medicines or commercial supplements to manage joint pain and inflammation. FlexPro MD® (FP-MD) combines krill oil, astaxanthin, and lower molecular weight hyaluronic acid to support joint health. A 12-week, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of FP-MD and placebo once daily in participants (n = 100) with mild osteoarthritis of the knee or hip joint. For the primary endpoint of joint pain score, per-protocol participants (n = 75) in the FP-MD group (n = 37) had a statistically significantly greater mean reduction from baseline in the Korean Visual Analog Scale (K-VAS) at week 12 compared with participants in the placebo group (n = 38) (20.8 ± 16.16 mm vs. 10.6 ± 17.58, p = 0.0105). The Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) total score was also significantly improved in the FP-MD group at week 12 compared with placebo (-13.0 ± 13.62 vs. -5.5 ± 18.08, p = 0.0489), especially an improvement in pain score (-2.5 ± 2.92 vs. -1.3 ± 3.94, p = 0.02635). FP-MD group had greater improvement in joint function scoring by investigator assessment (p = 0.0127) and by group participants (p = 0.0070). A statistically significantly greater number of patients reported adverse events in the placebo group compared with the FP-MD group (16% vs. 4%, p = 0.0455), most commonly gastrointestinal disorders in both of the groups. These findings suggest that FP-MD is well tolerated and can be effectively used to address joint pain in patients diagnosed with mild osteoarthritis, the main symptom of this condition.
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Euphausiacea , Osteoartritis , Humanos , Animales , Ácido Hialurónico/efectos adversos , Osteoartritis/tratamiento farmacológico , Artralgia/tratamiento farmacológico , Artralgia/etiologíaRESUMEN
Interleukin-1ß (IL-1ß) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1ß-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1ß activity by blocking IL-1ß-IL-1R1 interaction in OA. In this study, we report the anti-IL-1ß activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1ß-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1ß-IL-1R1 interaction by direct binding to IL-1ß using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1ß bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1ß-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1ß-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1ß-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1ß-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1ß-related diseases by hindering IL-1ß-IL-1R1 interaction and suppressing IL-1ß bioactivity.
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Antiinflamatorios , Osteoartritis , Ratas , Humanos , Animales , Interleucina-1beta/metabolismo , Antiinflamatorios/uso terapéutico , FN-kappa B/metabolismo , Inflamación/patología , Cartílago/metabolismo , Osteoartritis/inducido químicamente , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Condrocitos/metabolismo , Taninos/farmacología , Taninos/metabolismo , Células CultivadasRESUMEN
Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.
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Cartílago Articular , Osteoartritis , Ratones , Animales , Fosforilación , Poloxámero/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/uso terapéutico , Osteoartritis/patología , Cartílago Articular/metabolismo , Inyecciones IntraarticularesRESUMEN
PURPOSE: Patella tendon rupture with multi-ligament injury is a rare injury. We observed patients with patella tendon rupture (or patella inferior pole fracture) with multi-ligament injury. This study intends to inspect the mechanism of the injury and classify them. METHODS: This is a case series involving patients from two hospitals. Twelve patients who had patella tendon rupture (PTR) with multi-ligament injury were studied. RESULTS: The incidence of multi-ligament injury in patella tendon rupture patients found to be 13% in retrospective search. Two types of injury were observed. First type is relatively low energy injury involving ACL and patella tendon which does not involve rupture of PCL. Second type is high energy injury involving PCL and patella tendon. Treatment differed among the patients, due to severity of trauma. Two-staged operation was the basis of treatment. Patella tendon was repaired in first stage. Reconstruction of ligaments was done in second stage. The patients who had infection or stiffness did not have a second surgery. CONCLUSION: Patella tendon rupture with multi-ligament injury can be classified into low energy rotational injury and high energy dashboard injury. Two-staged surgery is the basis of treatment.
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Fracturas Óseas , Traumatismos de la Rodilla , Traumatismo Múltiple , Ligamento Rotuliano , Traumatismos de los Tejidos Blandos , Traumatismos de los Tendones , Humanos , Ligamento Rotuliano/cirugía , Ligamento Rotuliano/lesiones , Estudios Retrospectivos , Traumatismos de la Rodilla/cirugía , Rotura/cirugía , Traumatismos de los Tendones/cirugía , Fracturas Óseas/cirugía , Traumatismo Múltiple/cirugíaRESUMEN
Although activin receptor IIB (ACVR2B) is emerging as a novel pathogenic receptor, its ligand and assembled components (or assembly) are totally unknown in the context of osteoarthritis (OA) pathogenesis. The present results suggest that upregulation of ACVR2B and its assembly could affect osteoarthritic cartilage destruction. It is shown that the ACVR2B ligand, activin A, regulates catabolic factor expression through ACVR2B in OA development. Activin A Tg mice (Col2a1-Inhba) exhibit enhanced cartilage destruction, whereas heterozygous activin A KO mice (Inhba+/- ) show protection from cartilage destruction. In silico analysis suggests that the Activin A-ACVR2B axis is involved in Nox4-dependent ROS production. Activin A Tg:Nox4 KO (Col2a1-Inhba:Nox4-/- ) mice show inhibition of experimental OA pathogenesis. NOX4 directly binds to the C-terminal binding site on ACVR2B-ACVR1B and amplifies the pathogenic signal for cartilage destruction through SMAD2/3 signaling. Together, the findings reveal that the ACVR2B assembly, which comprises Activin A, ACVR2B, ACVR1B, Nox4, and AP-1-induced HIF-2α, accelerates OA development. Furthermore, it is shown that shRNA-mediated ACVR2B knockdown or trapping ligands of ACVR2B abrogate OA development by competitively disrupting the ACVR2B-Activin A interaction. These results suggest that the ACVR2B assembly is required to amplify osteoarthritic cartilage destruction and could be a potential therapeutic target in efforts to treat OA.
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Condrocitos , Osteoartritis , Animales , Ratones , Receptores de Activinas/metabolismo , Condrocitos/metabolismo , Condrocitos/patología , Ligandos , NADPH Oxidasa 4/metabolismo , Osteoartritis/metabolismoRESUMEN
Microfracture is a common technique that uses bone marrow components to stimulate cartilage regeneration. However, the clinical results of microfracture range from poor to good. To enhance cartilage healing, several reinforcing techniques have been developed, including porcine-derived collagen scaffold, hyaluronic acid, and chitosan. Autologous collagen-induced chondrogenesis (ACIC) is a single-step surgical technique for cartilage regeneration that combines gel-type atelocollagen scaffolding with microfracture. Even though ACIC is a relatively new technique, literature show excellent clinical results. In addition, all procedures of ACIC are performed arthroscopically, which is increasing in preference among surgeons and patients. The ACIC technique also is called the Shetty-Kim technique because it was developed from the works of A.A. Shetty and S.J. Kim. This is an up-to-date review of the history of ACIC.
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Cartílago Articular , Fracturas por Estrés , Humanos , Fracturas por Estrés/cirugía , Condrogénesis , Colágeno/uso terapéutico , AciclovirRESUMEN
BACKGROUND: Knee pain is one of the commonest symptoms in patients who attend the Orthopaedic outpatient clinics. Chondral defects result in a painful knee. Incidence of chondral defect is reported to be between 5 and 10% over the age of 40. It is well documented that chondral defects can lead to osteoarthritis. Early detection of these lesions and cartilage repair surgery can delay the onset of osteoarthritis. The purpose of this study is to highlight the incidence, associations and correlations between opposing cartilage defects in patients who present to the knee clinic with pain. METHODS: A retrospective analysis was carried out on patients who had Magnetic Resonance Imaging scans for painful knees between June 2017 and May 2019. About 227 consecutive knees were studied for the incidence of chondral defects, number of lesions, grade and size of lesion, geographical location and associated pathology in the knee. RESULTS: All the 227 patients had chondral lesions. Most patients had 2-3 lesions (66.1%) with patellar lesions (76.6%) being the commonest followed by medial femoral condyle (59.9%). Significant correlation was found in grade and size between opposing surface lesions in patella-trochlea, Medial Femoral Condyle-Medial Tibial Plateau and Lateral Femoral Condyle-Lateral Tibial Plateau. Females were more predisposed to patella lesions. Significance between age and lesions were established. CONCLUSION: Incidence of cartilage defects in the knee is very high. Kissing lesions must be considered when treating cartilage lesions. Volume index could be a promising method to quantify lesions.
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Enfermedades de los Cartílagos , Cartílago Articular , Traumatismos de la Rodilla , Osteoartritis , Femenino , Humanos , Adulto , Estudios Retrospectivos , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/lesiones , Traumatismos de la Rodilla/complicaciones , Traumatismos de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Enfermedades de los Cartílagos/diagnóstico por imagen , Enfermedades de los Cartílagos/patología , Imagen por Resonancia Magnética/métodos , DolorRESUMEN
Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle−Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10−37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17−6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.
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Cartílago Articular , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/cirugía , Sangre Fetal , Trasplante de Células Madre Mesenquimatosas/métodos , Artroscopía , Resultado del TratamientoRESUMEN
BACKGROUND: Patellar dislocation may cause cartilage defects of various sizes. Large defects commonly require surgical treatment; however, conventional treatments are problematic. CASE SUMMARY: A 15-year-old male with a large patellar cartilage defect due to patellar dislocation was treated via human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation. To our knowledge, this is the first report of this treatment for this purpose. The patient recovered well as indicated by good visual analog scale, International Knee Documentation Committee and McMaster Universities Osteoarthritis Index scores. Magnetic resonance imaging showed cartilage regeneration 18 mo postoperatively. CONCLUSION: Umbilical cord blood-derived hUCB-MSCs may be a useful treatment option for the repair of large patellar cartilage defects.
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Osteoarthritis (OA) is a degenerative joint disorder associated with inflammation, functional disability, and high socioeconomic costs. The development of effective therapies against inflammatory OA has been limited owing to its complex and multifactorial nature. The efficacy of Prussian blue nanozymes coated with Pluronic (PPBzymes), US Food and Drug Administration-approved components, and their mechanisms of action have been described in this study, and PPBzymes have been characterized as a new OA therapeutic. Spherical PPBzymes were developed via nucleation and stabilization of Prussian blue inside Pluronic micelles. A uniformly distributed diameter of approximately 204 nm was obtained, which was maintained after storage in an aqueous solution and biological buffer. This indicates that PPBzymes are stable and could have biomedical applications. In vitro data revealed that PPBzymes promote cartilage generation and reduce cartilage degradation. Moreover, intra-articular injections with PPBzymes into mouse joints revealed their long-term stability and effective uptake into the cartilage matrix. Furthermore, intra-articular PPBzymes injections attenuated cartilage degradation without exhibiting cytotoxicity toward the synovial membrane, lungs, and liver. Notably, based on proteome microarray data, PPBzymes specifically block the JNK phosphorylation, which modulates inflammatory OA pathogenesis. These findings indicate that PPBzymes might represent a biocompatible and effective nanotherapeutic for obstructing JNK phosphorylation.
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Proteínas Quinasas JNK Activadas por Mitógenos , Osteoartritis , Estados Unidos , Animales , Ratones , Fosforilación , Poloxámero , Osteoartritis/tratamiento farmacológicoRESUMEN
Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated Lactobacillus (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of Faecalibacterium which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.
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Cartílago Articular , Osteoartritis , Animales , Condrocitos/metabolismo , Cartílago Articular/metabolismo , Butiratos/metabolismo , Lactobacillus , Calidad de Vida , Modelos Animales de Enfermedad , Osteoartritis/metabolismo , Inflamación/metabolismo , Autofagia , Muerte CelularRESUMEN
BACKGROUND: Appropriate animal models of osteoarthritis (OA) are essential to develop new treatment modalities for OA. A combination of surgical and chemical induction could be appropriate for OA models. METHODS: Rabbit knee OA models developed by surgical induction (anterior cruciate ligament transection [ACLT]), chemical induction (monosodium iodoacetate [MIA] injection), and a combination of both were compared to assess compositional and structural destruction of the knee joint. Twenty-one New Zealand white rabbits were randomly divided into 3 groups to induce OA (group 1: ACLT, n = 3; group 2: MIA [3, 6, 9 mg] injection, n = 9; group 3: ACLT + MIA [3, 6, 9 mg] injection, n = 9). RESULTS: In all groups, the Modified Mankin score was significantly higher in the osteoarthritis-induced knee than in the control. Modified Mankin scores were compared by category. The ACLT group was observed to score high in cartilage structure. In the MIA group, chondrocytes and matrix staining showed higher scores, and the ACLT+MIA group scored higher in all categories for cartilage structure, chondrocytes, matrix staining, and tidemark integrity. The ACLT + 3 mg MIA showed definite OA characteristics such as cartilage surface destruction and degeneration of cartilage layers, and the ACLT + 6 mg MIA and ACLT + 9 mg MIA showed more prominent OA characteristics such as cartilage surface destruction, matrix disorganization, and osteophyte formation. CONCLUSION: The combination of MIA injection and ACLT could be an appropriate method for OA induction in rabbit models.
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Cartílago Articular , Osteoartritis de la Rodilla , Animales , Conejos , Ligamento Cruzado Anterior/cirugía , Modelos Animales de Enfermedad , Ácido Yodoacético , Articulación de la RodillaRESUMEN
Background: Tibial plateau fractures (TPFs) are a challenging type of fracture in orthopedic traumatology. We previously designed a plate (Patent Number: CN201520195596.5) for posterolateral TPF combined with posterior lateral collapse.. In this study, finite element analysis was used to compare the biomechanical characteristics of two internal fixation methods for posterolateral TPF. We investigated the support effect of the new steel plate on lateral TPFs combined with posterior TPFs. Methods: Two models of complex TPF were established. Model A was fixed with the new type of plate, and model B was fixed without the plate. Three axial loads of 500, 1,000, and 1,500 N were applied using FEA on the two fracture models (A and B) to analyze the data. Results: In model A, the maximum displacement at 500, 1,000, and 1,500 N was 0.085797, 0.17043, and 0.25465 mm, respectively; the maximum stress of the bone block was 11.285, 20.648, and 29.227 MPa, respectively; and the maximum strain of the bone block was 0.0012474, 0.007435, and 0.0035769 mm, respectively. The maximum displacement of the internal fixation was 0.096932, 0.18682, and 0.27655 mm, respectively; the maximum stress was 69.54, 112.1, and 155.71 MPa, respectively; and the maximum strain was 0.00066228, 0.0010676, and 0.0014829 mm, respectively. In model B, the maximum displacement of fractures at 500, 1,000, and 1,500 N was 0.15675, 0.29868, and 0.44017 mm, respectively; the maximum stress of the bone block was 6.5519, 12.575, and 18.842 MPa, respectively; and the maximum strain of the bone block was 0.0032554, 0.0074357, and 0.012146 mm, respectively. The maximum displacement of the screw was 0.14177, 0.27109, and 0.39849 mm, respectively; the maximum stress was 48.916, 92.251, and 135.27 MPa, respectively; and the maximum strain was 0.00046608, 0.00087893, and 0.0012887 mm, respectively. Conclusions: The fixation method using this type of plates and screws can replace other methods using two plates to fix complex TPF.
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BACKGROUND: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation. The targeting of CCL2-CCR2 is being studied as part of various topics including the treatment of OA. METHODS: In this study, we evaluated the potential therapeutic effects the sCCR2 E3 gene may exert on OA. The effects of sCCR2 E3 were investigated in animal experiments consisting of intra-articular injection of sCCR2 E3 in a monosodium iodoacetate (MIA)-induced OA rat model. The effects after intra-articular injection of sCCR2 E3 (fusion protein encoding 20 amino acids of the E3 domain of the CCL2 receptor) in a monosodium iodoacetate-induced OA rat model were compared to those in rats treated with empty vector (mock treatment) and full-length sCCR2. RESULTS: Pain improved with expression of the sCCR2 gene. Improved bone resorption upon sCCR2 E3 gene activation was confirmed via bone analyses using micro-computed tomography. Histologic analyses showed that the sCCR2 E3 gene exerted protective effects against cartilage damage and anti-inflammatory effects on joints and the intestine. CONCLUSIONS: These results show that sCCR2 E3 therapy is effective in reducing pain severity, inhibiting cartilage destruction, and suppressing intestinal damage and inflammation. Thus, sCCR2 E3 may be a potential therapy for OA.
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Cartílago Articular , Osteoartritis , Aminoácidos/metabolismo , Animales , Antiinflamatorios/farmacología , Cartílago/patología , Cartílago Articular/patología , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Terapia Genética , Inflamación/metabolismo , Ácido Yodoacético/metabolismo , Ácido Yodoacético/toxicidad , Osteoartritis/diagnóstico por imagen , Osteoartritis/genética , Osteoartritis/terapia , Dolor/patología , Ratas , Receptores CCR2/genética , Receptores CCR2/metabolismo , Receptores de Quimiocina/metabolismo , Microtomografía por Rayos XRESUMEN
Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)2D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1ß, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.
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Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1ß, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.
RESUMEN
Articular cartilage has unique biological and biomechanical characteristics. Damage to this tissue fails to heal spontaneously, leading to progressive arthritis. Cartilage repair techniques have been looked forward to in the treatment of significant cartilage injuries. Cell-based regenerative techniques like the two-staged cultured chondrocytes and single-stage mesenchymal cell transplantation have been tried with varying results and limitations. We study the outcomes of cultured bone marrow derived MSCs in the treatment of articular cartilage defects of the knee in comparison to autologous cultured chondrocyte implantation (ACI). Both cultured MSC and ACI treatment methods resulted in significant improvements in patient reported outcome measures (PROMs). There was no difference in the PROMs, MOCART scores, T2∗ mapping and dGEMRIC values between the groups. Use of cultured MSCs leads to good clinical outcomes similar to ACI and represents a promising treatment to restore the articular cartilage in the knee.