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OBJECTIVES: The purpose of this study was to assess morphological and quantitative changes of the anterior cruciate ligament (ACL) and cartilage after ACL repair. METHODS: 7T MRI of the knee was acquired in 31 patients 1.5 years after ACL repair and in 13 controls. Proton density-weighted images with fat saturation (PD-fs) were acquired to assess ACL width, signal intensity, elongation, and fraying. T2/T2* mapping was performed for assessment of ACL and cartilage. Segmentation of the ACL, femoral, and tibial cartilage was carried out at 12 ROIs. The outcome evaluation consisted of the Lysholm Knee Score and International Knee Documentation Committee (IKDC) subjective score and clinical examination. RESULTS: ACL showed a normal signal intensity in 96.8% and an increased width in 76.5% after repair. Fraying occurred in 22.6% without having an impact on the clinical outcome (Lysholm score: 90.39 ± 9.75, p = 0.76 compared to controls). T2 analysis of the ACL revealed no difference between patients and controls (p = 0.74). Compared to controls, assessment of the femoral and tibial cartilage showed a significant increase of T2* times in all ROIs, except at the posterolateral femur. Patients presented a good outcome in clinical examination with a Lysholm score of 87.19 ± 14.89 and IKDC of 80.23 ± 16.84. CONCLUSION: T2 mapping results suggest that the tissue composition of the ACL after repair is similar to that of a native ACL after surgery, whereas the ACL exhibits an increased width. Fraying of the ACL can occur without having any impact on functional outcomes. T2* analysis revealed early degradation at the cartilage. CLINICAL RELEVANCE STATEMENT: MRI represents a noninvasive diagnostic tool for the morphological and compositional assessment of the anterior cruciate ligament after repair, whereas knowledge about post-surgical alterations is crucial for adequate imaging interpretation. KEY POINTS: ⢠There has been renewed interest in repairing the anterior cruciate ligament with a proximally torn ligament. ⢠T2 times of the anterior cruciate ligament do not differ between anterior cruciate ligament repair patients and controls. ⢠T2 mapping may serve as a surrogate for the evaluation of the anterior cruciate ligament after repair.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Adulto , Reconstrucción del Ligamento Cruzado Anterior/métodos , Resultado del Tratamiento , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Persona de Mediana Edad , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/cirugía , Adulto Joven , Estudios de Casos y Controles , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , AdolescenteRESUMEN
BACKGROUND: The correct diagnosis and treatment of the atlanto-occipital dislocation (AOD) remains a major challenge. OBJECTIVE: To evaluate the different radiological diagnostic criteria for AOD and discuss potential treatment strategies based on a case with AOD and additional fracture of the atlas. MATERIAL AND METHODS: A 29-year-old male patient is presented who suffered from AOD with concomitant fracture of the anterior and posterior arches of the atlas with rotational atlantoaxial dislocation following an accident in forestry. The following parameters were evaluated for the diagnosis and assessment of postoperative reduction: Powers ratio, the Xlines-method, Wackenheim line, basion-dens interval (BDI), basion-axial interval (BAI) and occipital condyle-C1 interval (CCI). RESULTS: Stabilization was performed by occipitocervical spondylodesis from C0 to C2/3. For final reduction it was necessary to reduce the malrotation of the atlas. In the presented case, the revised CCI proved to be a sensitive and valid yet practical parameter. Powers' ratio and the BDI were less suited for assessing the diagnosis. The Xlines-method, Wackenheim line and the BAI did not adequately detect the pathological situation. DISCUSSION: The AOD is a severe injury requiring immediate correct diagnosis for later adequate treatment results. Among the published parameters, the revised CCI proved to be a practical and valid parameter to detect AOD. For definitive treatment, the operative occipitocervical stabilization is regarded as the method of choice.
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Articulación Atlantooccipital , Luxaciones Articulares , Traumatismos Vertebrales , Masculino , Humanos , Adulto , Articulación Atlantooccipital/diagnóstico por imagen , Luxaciones Articulares/diagnóstico , Traumatismos Vertebrales/diagnóstico por imagen , Radiografía , Hueso Occipital/lesionesRESUMEN
Gelsolin (GSN) is an actin-binding protein involved in cell formation, metabolism and wound closure processes. Since this protein is known to play a role in arthritis, here we investigate how the synovial membrane with its specific synoviocytes contributes to the expression of GSN and how the amount of GSN expressed is modulated by different types of arthritis. Synovial membranes from adult healthy subjects and patients with rheumatoid arthritis (RA) and osteoarthritis (OA) are analyzed by immunofluorescence, Western blot and ELISA. Macrophage-like synoviocytes (MLS) and fibroblast-like synoviocytes (FLS) were isolated, cultured and analyzed for their potential to produce and secrete GSN. In addition, the GSN concentrations in the synovial fluid of various forms of arthritis are determined by ELISA. GSN is produced by the healthy and arthritic synovial membranes. Both forms of synoviocytes (MLS and FLS) release GSN. The results show that there is a significant reduction in GSN in the synovial fluid in adult patients with OA. This reduction is also detectable in adult patients with RA but is not as evident. In juvenile arthritis, there is a slight increase in GSN concentration in the synovial fluid. This study shows that primary MLS and FLS express GSN and that these cells, in addition to articular chondrocytes, contribute to GSN levels in synovial fluid. Furthermore, GSN concentrations are modulated in different types of arthritis. Further studies are needed to fully understand how GSN is involved in joint homeostasis.
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BACKGROUND: Continuous passive motion (CPM) and active knee joint motion devices are commonly applied after various surgical procedures. Despite the growing use of active motion devices, there is a paucity of data comparing plantar loads between the different mobilization techniques. The aim of this study was to investigate foot loads during knee joint mobilization in continuous passive and active knee joint motion devices and to compare this data to the physiological load of full weight-bearing. PATIENTS/MATERIAL AND METHODS: Fifteen healthy participants (7 women and 8 men, 25â±â3 years, 66â±â6âkg, 175â±â10âcm, BMI 21.9â±â2) were recruited. Plantar loads were measured via dynamic pedobarography using a continuous passive motion device (ARTROMOT-K1, ORMED GmbH, Freiburg, Germany) and an active motion device (CAMOped, OPED AG, Cham, Switzerland), each with a restricted range of motion of 0-0-90° (ex/flex) and free ROM for the knee joint. For the active motion device, cycles were performed at four different resistance levels (0-III). Data were assessed using the pedar® X system (Novel Inc., Munich, Germany), which monitors loads from the foot-sole interface. Force values were compared between motion devices and normal gait, which served as the reference for conditions of full weight-bearing. P-values of <â0.05 were considered statistically signiï¬cant. RESULTS: Normal gait revealed peak forces of 694â±â96 N, defined as 100â%. The CPM device produced plantar forces of less than 1.5 N. Using the active motion device in the setting of 0-0-90° produced foot loads of <â1.5 N (resistance 0-II) and 3.4â±â9.3 N with a resistance of III (pâ<â0.001). Conditions of free ROM resulted in foot loads of 4.5â±â4.5 N (resistance 0), 7.7â± 10.7 N (resistance I), 6.7â±â10.4 (resistance II) and 6.7â±â6.9 N with a resistance of III (pâ<â0.001), corresponding to 0.6â%, 1.1â%, 1.0â% and 1.0â% of full weight-bearing, respectively. CONCLUSION: Motion exercises of the knee joint can be performed both with passive and active devices in accordance with strict weight-bearing restrictions, which are often recommended by surgeons. Also, active motion devices can be used when the ankle joint or foot have to be offloaded. Further studies assessing intraarticular joint load conditions have to be performed to confirm the findings obtained in this study.
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Pie , Articulación de la Rodilla , Femenino , Alemania , Humanos , Masculino , Rango del Movimiento Articular , SuizaRESUMEN
Fibroblasts are key effector cells in tissue remodeling. They remain persistently activated in fibrotic diseases, resulting in progressive deposition of extracellular matrix. Although fibroblast activation may be initiated by external factors, prolonged activation can induce an "autonomous," self-maintaining profibrotic phenotype in fibroblasts. Accumulating evidence suggests that epigenetic alterations play a central role in establishing this persistently activated pathologic phenotype of fibroblasts. We demonstrated that in fibrotic skin of patients with systemic sclerosis (SSc), a prototypical idiopathic fibrotic disease, TGF-ß induced the expression of DNA methyltransferase 3A (DNMT3A) and DNMT1 in fibroblasts in a SMAD-dependent manner to silence the expression of suppressor of cytokine signaling 3 (SOCS3) by promoter hypermethylation. Downregulation of SOCS3 facilitated activation of STAT3 to promote fibroblast-to-myofibroblast transition, collagen release, and fibrosis in vitro and in vivo. Reestablishment of the epigenetic control of STAT3 signaling by genetic or pharmacological inactivation of DNMT3A reversed the activated phenotype of SSc fibroblasts in tissue culture, inhibited TGF-ß-dependent fibroblast activation, and ameliorated experimental fibrosis in murine models. These findings identify a pathway of epigenetic imprinting of fibroblasts in fibrotic disease with translational implications for the development of targeted therapies in fibrotic diseases.
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Epigénesis Genética , Miofibroblastos/metabolismo , Factor de Transcripción STAT3/metabolismo , Esclerodermia Sistémica/metabolismo , Transducción de Señal , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , ADN (Citosina-5-)-Metiltransferasa 1/biosíntesis , ADN (Citosina-5-)-Metiltransferasas/biosíntesis , ADN Metiltransferasa 3A , Femenino , Fibrosis , Regulación Enzimológica de la Expresión Génica , Humanos , Masculino , Ratones , Miofibroblastos/patología , Esclerodermia Sistémica/patologíaRESUMEN
BACKGROUND: The treatment of fractures of the tibial plateau or distal femur often represents a severe problem in geriatric patients. In particular, complex fracture types and concomitant severe osteoporosis are confronted with inferior results following internal fixation. Therefore, primary arthroplasty is increasingly propagated for such particular cases. PATIENTS, MATERIALS AND METHODS: In 16 patients suffering from fractures of the distal femur or tibial plateau were treated either by internal fixation (n = 8) or primary arthroplasty (n = 8). The outcome of each case was retrospectively analysed according to clinical and economic criteria. RESULTS: In the investigated geriatric patients, primary arthroplasty was significantly superior to internal fixation regarding mobilisation and range of motion without being inferior in cost-effectiveness. CONCLUSION: Compared to internal fixation, primary arthroplasty represents an efficient and cost-effective therapeutical option for the treatment of complex fractures of the distal femur or tibial plateau of the elderly patient.
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Artroplastia de Reemplazo de Rodilla , Fracturas del Fémur , Fijación Interna de Fracturas , Fracturas de la Tibia , Anciano , Fracturas del Fémur/cirugía , Humanos , Articulación de la Rodilla , Estudios Retrospectivos , Fracturas de la Tibia/cirugía , Resultado del TratamientoRESUMEN
Objective: It is known that recombinant human gelsolin (rhuGSN) supports wound closure and migration processes in avascular tissue. Since articular cartilage degradation plays an important role in osteoarthritis (OA), we are investigating how rhuGSN affects regeneration processes in human articular cartilage and represents a promising new therapeutic approach for the treatment of OA. Methods: Primary human chondrocytes (phCs) from articular knee cartilage were cultured with different concentrations of rhuGSN to analyse its direct effect in vitro. In addition, phCs were stimulated with 10 ng/mL IL-1ß or TNF-α to simulate osteoarthritis in vitro and treated with different concentrations of rhuGSN to investigate the beneficial effect in disease treatment. Cytokine secretion and gene expression as well as wound assays were performed. Results: GSN significantly promotes wound closure in phCs after 60 h compared to untreated cells. After 24 h treatment with 30 µg/mL rhuGSN, TGF-ß secretion increases significantly in the in vitro osteoarthritis model. Gene expression of MMP1 as well as SPARC is reduced in chondrocytes due to treatment with GSN in the OA model. At the same time, CXCR4 expression increases significantly after 24 h treatment with 3 µg/mL GSN. Conclusion: In the in vitro model of osteoarthritis, rhuGSN promotes wound closure of chondrocytes by a supported migration as well as expression of reconstructive and down regulated expression of deconstructive genes concentration dependently. Further experiments are needed to fully understand the beneficial effect of gelsolin on human chondrocytes and to verify this promising approach for a pharmacological treatment of osteoarthritis.
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OBJECTIVE: Trefoil factor family peptide 3 (TFF3) has been shown to support catabolic functions in cases of osteoarthritis (OA). As in joint physiology and diseases such as OA, the synovial membrane (SM) of the joint capsule also plays a central role. We analyze the ability of SM to produce TFF compare healthy SM and its secretion product synovial fluid (SF) with SM and SF from patients suffering from OA or rheumatoid arthritis (RA). METHODS: Real-time PCR and ELISA were used to measure the expression of TFFs in healthy SM and SM from patients suffering from OA or RA. For tissue localization, we investigated TFF1-3 in differently aged human SM of healthy donors by means of immunohistochemistry, real-time PCR and Western blot. RESULTS: Only TFF3 but not TFF1 and -2 was expressed in SM from healthy donors as well as cases of OA or RA on protein and mRNA level. In contrast, all three TFFs were detected in all samples of SF on the protein level. No significant changes were observed for TFF1 at all. TFF2 was significantly upregulated in RA samples in comparison to OA samples. TFF3 protein was significantly downregulated in OA samples in comparison to healthy samples and cases of RA significantly upregulated compared to OA. In contrast, in SM TFF3 protein was not significantly regulated. CONCLUSION: The data demonstrate the production of TFF3 in SM. Unexpectedly, SF contains all three known TFF peptides. As neither articular cartilage nor SM produce TFF1 and TFF2, we speculate that these originate with high probability from blood serum.
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Artritis Reumatoide/metabolismo , Osteoartritis/metabolismo , Líquido Sinovial/metabolismo , Membrana Sinovial/metabolismo , Factor Trefoil-1/metabolismo , Factor Trefoil-2/metabolismo , Factor Trefoil-3/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Donantes de Tejidos , Factor Trefoil-1/genética , Factor Trefoil-2/genética , Factor Trefoil-3/genéticaRESUMEN
Closed circulatory systems (CCS) underlie the function of vertebrate organs, but in long bones their structure is unclear, although they constitute the exit route for bone marrow (BM) leukocytes. To understand neutrophil emigration from BM, we studied the vascular system of murine long bones. Here we show that hundreds of capillaries originate in BM, cross murine cortical bone perpendicularly along the shaft and connect to the periosteal circulation. Structures similar to these trans-cortical-vessels (TCVs) also exist in human limb bones. TCVs express arterial or venous markers and transport neutrophils. Furthermore, over 80% arterial and 59% venous blood passes through TCVs. Genetic and drug-mediated modulation of osteoclast count and activity leads to substantial changes in TCV numbers. In a murine model of chronic arthritic bone inflammation, new TCVs develop within weeks. Our data indicate that TCVs are a central component of the CCS in long bones and may represent an important route for immune cell export from the BM.
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Huesos/irrigación sanguínea , Capilares/fisiología , Microcirculación , Flujo Sanguíneo Regional , Animales , Médula Ósea/irrigación sanguínea , Humanos , Ratones , Ratones Endogámicos DBARESUMEN
The aim of the study was to explore the possible role of Trefoil Factor Family peptide 3 (TFF3) for skeletal repair. The expression of TFF3 was analyzed in human joint tissues as well as in a murine bone fracture model. Serum levels of TFF3 following a defined skeletal trauma in humans were determined by ELISA. The mRNA expression of TFF3 was analyzed under normoxia and hypoxia. Expression analysis after stimulation of human mesenchymal progenitor cells (MPCs) with TFF3 was performed by RT2 Profiler PCR Array. The effect of recombinant human (rh)TFF3 on MPCs was analysed by different migration and chemotaxis assays. The effect on cell motility was also visualized by fluorescence staining of F-Actin. TFF3 was absent in human articular cartilage, but strongly expressed in the subchondral bone and periosteum of adult joints. Strong TFF3 immunoreactivity was also detected in murine fracture callus. Serum levels of TFF3 were significantly increased after skeletal trauma in humans. Expression analysis demonstrated that rhTFF3 significantly decreased mRNA of ROCK1. Wound healing assays showed increased cell migration of MPCs by rhTFF3. The F-Actin cytoskeleton was markedly influenced by rhTFF3. Cell proliferation was not increased by rhTFF3. The data demonstrate elevated expression of TFF3 after skeletal trauma. The stimulatory effects on cell motility and migration of MPCs suggest a role of TFF3 in skeletal repair.
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Citoesqueleto de Actina/metabolismo , Huesos/fisiología , Movimiento Celular , Factor Trefoil-3/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Huesos/metabolismo , Femenino , Curación de Fractura , Regulación de la Expresión Génica , Humanos , Hipoxia , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Factor Trefoil-3/fisiología , Quinasas Asociadas a rho/genéticaRESUMEN
Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1- mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.
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Articulaciones/citología , Macrófagos/citología , Macrófagos/fisiología , Membrana Sinovial/citología , Sinoviocitos/citología , Sinoviocitos/fisiología , Uniones Estrechas/fisiología , Animales , Artritis/inmunología , Artritis/patología , Receptor 1 de Quimiocinas CX3C/análisis , Receptor 1 de Quimiocinas CX3C/metabolismo , Rastreo Celular , Femenino , Perfilación de la Expresión Génica , Humanos , Inflamación/inmunología , Inflamación/patología , Articulaciones/patología , Macrófagos/clasificación , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Análisis de Componente Principal , RNA-Seq , Análisis de la Célula Individual , Sinoviocitos/clasificación , Sinoviocitos/metabolismo , Transcriptoma/genéticaRESUMEN
Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs.
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Diferenciación Celular/genética , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis/genética , Fibrosis/patología , Proteínas Proto-Oncogénicas/metabolismo , Transactivadores/metabolismo , Animales , Secuencia de Bases , Epigénesis Genética , Femenino , Humanos , Inflamación/genética , Inflamación/patología , Masculino , Ratones , Regiones Promotoras Genéticas/genética , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Transactivadores/antagonistas & inhibidoresRESUMEN
PURPOSE: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment. MATERIAL AND METHODS: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined. RESULTS: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%. CONCLUSIONS: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results.
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Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Adolescente , Adulto , Anciano , Enfermedades de los Cartílagos/fisiopatología , Cartílago Articular/patología , Cartílago Articular/fisiología , Femenino , Fémur/fisiopatología , Fémur/cirugía , Humanos , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Regeneración , Sistema de Registros , Tibia/fisiopatología , Tibia/cirugía , Adulto JovenRESUMEN
IMPACT STATEMENT: The repair of large articular cartilage lesions is still a major challenge. In particular, the fixation of the grafts to the subchondral bone plate represents an unresolved problem. In this work, we present a completely novel concept based on a modular lattice, combining building blocks of different ceramic materials, anchoring pins and space for cell-loaded hydrogels or other scaffold materials. This concept targets not only circumscribed cartilage defects but also large osteoarthritic lesions. It spans the bridge between cell therapy and artificial joint arthroplasty, and thus is of significant medical and socioeconomic impact.
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Articulaciones/fisiología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Adulto , Anciano , Anciano de 80 o más Años , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Cerámica/farmacología , Colágeno/farmacología , Humanos , Hidrogeles/farmacología , Implantes Experimentales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Persona de Mediana Edad , Resistencia a la Tracción , Microtomografía por Rayos XRESUMEN
OBJECTIVE: Surfactant Proteins (SPs) are well known from lung and form, along with phospholipids, a surface-active-layer at the liquid-air-interface of the alveolar lining. They play a major protective role by lowering surface tension, activating innate and adaptive immune defense at the lung mucosal interface, especially during infection. We analyzed the regulation of SPs in human and mouse articular chondrocytes, synoviocytes, and synovial fluid under healthy and inflammatory conditions, as well as in tissues of patients suffering from osteoarthritis and rheumatoid arthritis. METHODS: Immunohistochemistry, RT-PCR, qRT-PCR, ELISA, Western blotting were performed in cell cultures and tissue samples to determine localization, regulation, and concentration of SPs. RESULTS: All four SPs, were expressed by healthy human and mouse articular chondrocytes and synoviocytes and were also present in synovial fluid. Treatment with inflammatory mediators like IL-1ß and TNF-α led to short-term upregulation of individual SPs in vitro. In tissues from patients with osteoarthritis and rheumatoid arthritis, protein levels of all four SPs increased significantly compared to the controls used. CONCLUSION: These results show the distribution and amount of SPs in tissues of articular joints. They are produced by chondrocytes and synoviocytes and occur in measurable amounts in synovial fluid. All four SPs seem to be differently regulated under pathologic conditions. Their physiological functions in lowering surface tension and immune defense need further elucidation and make them potential candidates for therapeutic intervention.
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Artritis Reumatoide/metabolismo , Cartílago Articular/metabolismo , Osteoartritis/metabolismo , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Proteína C Asociada a Surfactante Pulmonar/metabolismo , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Líquido Sinovial/metabolismo , Membrana Sinovial/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/patología , Cartílago Articular/patología , Línea Celular Transformada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/patología , Membrana Sinovial/patologíaRESUMEN
BACKGROUND: Despite the general success of total knee arthroplasty (TKA) regarding patient-reported outcome measures, studies investigating gait function have shown diverse functional outcomes. Mobile sensor-based systems have recently been employed for accurate clinical gait assessments, as they allow a better integration of gait analysis into clinical routines as compared to laboratory based systems. RESEARCH QUESTION: In this study, we sought to examine whether an accurate assessment of gait function of knee osteoarthritis patients with respect to surgery outcome evaluation after TKA using a mobile sensor-based gait analysis system is possible. METHODS: A foot-worn sensor-based system was used to assess spatio-temporal gait parameters of 24 knee osteoarthritis patients one day before and one year after TKA, and in comparison to matched control participants. Patients were clustered into positive and negative responder groups using a heuristic approach regarding improvements in gait function. Machine learning was used to predict surgery outcome based on pre-operative gait parameters. RESULTS: Gait function differed significantly between controls and patients. Patient-reported outcome measures improved significantly after surgery, but no significant global gait parameter difference was observed between pre- and post-operative status. However, the responder groups could be correctly predicted with an accuracy of up to 89% using pre-operative gait parameters. Patients exhibiting high pre-operative gait function were more likely to experience a functional decrease after surgery. Important gait parameters for the discrimination were stride time and stride length. SIGNIFICANCE: The early identification of post-surgical functional outcomes of patients is of great importance to better inform patients pre-operatively regarding surgery success and to improve post-surgical management.
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Artroplastia de Reemplazo de Rodilla/métodos , Análisis de la Marcha/métodos , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Acelerometría/métodos , Anciano , Femenino , Marcha/fisiología , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Sensibilidad y Especificidad , Análisis Espacio-Temporal , Resultado del TratamientoRESUMEN
Uncontrolled activation of TGFß signaling is a common denominator of fibrotic tissue remodeling. Here we characterize the tyrosine phosphatase SHP2 as a molecular checkpoint for TGFß-induced JAK2/STAT3 signaling and as a potential target for the treatment of fibrosis. TGFß stimulates the phosphatase activity of SHP2, although this effect is in part counterbalanced by inhibitory effects on SHP2 expression. Stimulation with TGFß promotes recruitment of SHP2 to JAK2 in fibroblasts with subsequent dephosphorylation of JAK2 at Y570 and activation of STAT3. The effects of SHP2 on STAT3 activation translate into major regulatory effects of SHP2 on fibroblast activation and tissue fibrosis. Genetic or pharmacologic inactivation of SHP2 promotes accumulation of JAK2 phosphorylated at Y570, reduces JAK2/STAT3 signaling, inhibits TGFß-induced fibroblast activation and ameliorates dermal and pulmonary fibrosis. Given the availability of potent SHP2 inhibitors, SHP2 might thus be a potential target for the treatment of fibrosis.
Asunto(s)
Fibroblastos/metabolismo , Fibroblastos/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Adulto , Anciano , Animales , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Femenino , Fibroblastos/efectos de los fármacos , Fibrosis , Humanos , Janus Quinasa 2/metabolismo , Masculino , Ratones Noqueados , Persona de Mediana Edad , Especificidad de Órganos , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Quinolinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/patología , Transducción de Señal/efectos de los fármacos , Adulto JovenRESUMEN
OBJECTIVES: The anterior talofibular ligament (ATFL) is the most frequently injured ligament during inversion strains of the ankle. The purpose of this study was to evaluate the feasibility of acoustic radiation force impulse (ARFI) elastography and to determine the in vivo mechanical properties of the ATFL in healthy athletes. METHODS: Sixty healthy athletes (32 female, 28 male; 28.9 ± 2.1 years) were recruited from the medical and sports faculty. ARFI values, represented as shear wave velocities (SWVs) as well as conventional ultrasound were obtained for the ATFL in neutral ankle position. A clinical assessment was performed in which the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Score and the functional ankle ability measure (FAAM) were collected. Interobserver and intraobserver reliability (repeated sessions and repeated days) were assessed using an intra class correlation coefficient (ICC) and typical error (TE) calculation in absolute (TE) and relative units as coefficient of the variation (CV). RESULTS: SWV values of the ATFL had an average velocity of 1.79 ± 0.20 m/s for all participants, with an average of 1.72 ± 0.36 m/s for females and 1.85 ± 0.31 m/s for males. The interobserver and intraobserver reliability revealed an ICC of 0.902 and 0.933 (TE of 0.67 (CV: 5.2%) and 0.52 (CV: 3.84%)), respectively. FAAM and AOFAS revealed the best possible scores. CONCLUSION: ARFI seems to be a valuable diagnostic modality and represents a promising imaging marker for the assessment and monitoring of ankle ligaments in the context of acute and chronic ankle instabilities; ARFI could also be used to investigate loading or sport dependent adaptions.