RESUMEN
OBJECTIVE: To examine if relationships between knee osteoarthritis (OA) progression with knee moments and muscle activation during gait vary between patients with non-traumatic and post-traumatic knee OA. DESIGN: This longitudinal study included participants with non-traumatic (n = 17) and post-traumatic (n = 18) knee OA; the latter group had a previous anterior cruciate ligament rupture. Motion capture cameras, force plates, and surface electromyography measured knee moments and lower extremity muscle activation during gait. Cartilage volume change were determined over 2 years using magnetic resonance imaging in four regions: medial and lateral plateau and condyle. Linear regression analysis examined relationships between cartilage change with gait metrics (moments, muscle activation), group, and their interaction. RESULTS: Measures from knee adduction and rotation moments were related to lateral condyle cartilage loss in both groups, and knee adduction moment to lateral plateau cartilage loss in the non-traumatic group only [ß = -1.336, 95% confidence intervals (CI) = -2.653 to -0.019]. Generally, lower levels of stance phase muscle activation were related to greater cartilage loss. The relationship between cartilage loss in some regions with muscle activation characteristics varied between non-traumatic and post-traumatic groups including for: lateral hamstring (lateral condyle ß = 0.128, 95%CI = 0.003 to 0.253; medial plateau ß = 0.199, 95%CI = 0.059 to 0.339), rectus femoris (medial condyle ß = -0.267, 95%CI = -0.460 to -0.073), and medial hamstrings (medial plateau; ß = -0.146, 95%CI = -0.244 to -0.048). CONCLUSION: Findings indicate that gait risk factors for OA progression may vary between patients with non-traumatic and post-traumatic knee OA. These OA subtypes should be considered in studies that investigate gait metrics as risk factors for OA progression.
Asunto(s)
Cartílago Articular/diagnóstico por imagen , Marcha/fisiología , Músculo Esquelético/fisiología , Osteoartritis de la Rodilla/fisiopatología , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Estudios de Cohortes , Progresión de la Enfermedad , Electromiografía , Femenino , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Factores de RiesgoRESUMEN
Tungsten is incorporated in many industrial goods, military applications and medical devices due to its ability to impart flexibility, strength and conductance to materials. Emerging evidence has questioned the safety of tungsten exposure as studies have demonstrated it can promote tumour formation, induce pulmonary disease and alter immune function. Although tungsten is excreted from the body it can accumulate in certain organs such as the brain, colon, liver, kidneys, spleen and bones, where most of the bioaccumulation occurs. Whether prolonged tungsten exposure leads to accumulation in other tissues is unknown. The present study demonstrated that mice exposed to 15 ppm sodium tungstate for 4 weeks in their drinking water showed comparable accumulation in both the bony vertebrae and intervertebral discs (IVDs). Lumbar IVD height was significantly reduced in tungsten-exposed mice and accompanied by decreased proteoglycan content and increased fibrosis. In addition to catabolic enzymes, tungsten also increased the expression of the inflammatory cytokines IL-1ß and tumour necrosis factor (TNF)-α as well as the neurotrophic factors nerve growth factor (NGF) and brain-derived nerve factor (BDNF) in IVD cells. Tungsten significantly increased the presence of nociceptive neurons at the endplates of IVDs as observed by the expression of calcitonin gene-related peptide (CGRP) and anti-protein gene product 9.5 (PGP9.5) in endplate vessels. The present study provided evidence that tungsten may enhance disc degeneration and fibrosis as well as increase the expression of markers for pain. Therefore, tungsten toxicity may play a role in disc degeneration disease.
Asunto(s)
Inflamación/metabolismo , Degeneración del Disco Intervertebral/inducido químicamente , Disco Intervertebral/efectos de los fármacos , Dolor/metabolismo , Tungsteno/efectos adversos , Regulación hacia Arriba/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Citocinas/metabolismo , Fibrosis/metabolismo , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Osteoarthritis (OA) is a disease of diarthrodial joints associated with extracellular matrix proteolytic degradation under inflammatory conditions, pain and disability. Currently, there is no therapy to prevent, reverse or modulate the disease course. The present study aimed at evaluating the regenerative potential of Link N (LN) in human OA cartilage in an inflammatory milieu and determining if LN could affect pain-related behaviour in a knee OA mouse injury model. Osteo-chondro OA explants and OA chondrocytes were treated with LN in the presence of interleukin-1ß (IL-1ß) to simulate an osteoarthritic environment. Quantitative von Frey polymerase chain reaction and Western blotting were performed to determine the effect of LN on matrix protein synthesis, catabolic enzymes, cytokines and nerve growth factor expression. Partial medial meniscectomy (PMM) was performed on the knee of C57BL/6 mice and, 12 weeks post-surgery, mice were given a 5 µg intra-articular injection of LN or phosphate-buffered saline. A von Frey test was conducted over 24 h to measure the mechanical allodynia in the hind paw. LN modulated proteoglycan and collagen synthesis in human OA cartilage through inhibition of IL-1ß-induced biological effects. LN also supressed IL-1ß-induced upregulation of cartilage-degrading enzymes and inflammatory molecules in OA chondrocytes. Upon investigation of the canonical signalling pathways IL-1ß and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), LN resulted to significantly inhibit NF-κB activation in a dose-dependent manner. In addition, LN suppressed mechanical allodynia in an OA PMM mouse model. Results supported the concept that LN administration could provide therapeutic potential in OA.
Asunto(s)
Cartílago Articular/patología , Interleucina-1beta/farmacología , Osteoartritis/patología , Péptidos/farmacología , Anciano , Animales , Conducta Animal/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Colágeno Tipo II/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Glicosaminoglicanos/metabolismo , Humanos , Hidroxiprolina/metabolismo , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/patología , Ratones Endogámicos C57BL , Persona de Mediana Edad , Dolor/patología , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: The objective was to compare muscle activation and knee mechanics during gait between participants with non-traumatic knee osteoarthritis (OA), post-traumatic knee OA, and healthy adults. DESIGN: Participants with non-traumatic knee OA (n = 22), post-traumatic knee OA (n = 19), and healthy adults (n = 22) completed gait trials for this observational, cross-sectional study. Post-traumatic OA group had a history of traumatic anterior cruciate ligament (ACL) rupture. Surface electromyography (EMG) measured activation of seven lower extremity muscles. Motion capture cameras and force plates measured motion and force data. Principal component analysis (PCA) determined waveform characteristics (principal components) from EMG, knee angle, and knee external moment waveforms. Analysis of variance (ANOVA) examined group differences in principal component scores (PC-scores). Regression analyses examined if a variable that coded for OA group could predict PC-scores after accounting for disease severity, alignment, and lateral OA. RESULTS: There was lower gastrocnemius EMG amplitudes (P < 0.01; ANOVA) in the post-traumatic OA group compared to healthy group. Non-traumatic OA group had higher vastus lateralis, vastus medialis, and rectus femoris EMG compared to post-traumatic OA group (P = 0.01 to 0.04) in regression analyses. Also, non-traumatic OA group had higher and prolonged lateral hamstring EMG compared to healthy (P = 0.03; ANOVA) and post-traumatic OA (P = 0.04; regression) groups respectively. The non-traumatic OA group had lower knee extension (P < 0.05) and medial rotation (P < 0.05) moments than post-traumatic and healthy groups. CONCLUSIONS: Muscle activation and knee mechanics differed between participants with non-traumatic and post-traumatic knee OA and healthy adults. These OA subtypes had differences in disease characteristics that may impact disease progression.
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Marcha/fisiología , Traumatismos de la Rodilla/fisiopatología , Músculo Esquelético/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Adulto , Anciano , Ligamento Cruzado Anterior/fisiopatología , Fenómenos Biomecánicos , Estudios de Casos y Controles , Estudios Transversales , Electromiografía , Femenino , Humanos , Traumatismos de la Rodilla/complicaciones , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/etiologíaRESUMEN
Osteoarthritis (OA) is a degenerative joint disease characterised by a progressive degradation of articular cartilage and underlaying bone and is associated with pain and disability. Currently, there is no medical treatment to reverse or even retard OA. Based on our previous reports, where we establish the repair potential of short Link N (sLN) in the intervertebral disc, a cartilage-like tissue, we hypothesise that sLN may hold similar promises in the repair of articular cartilage. This study aimed to determine if sLN, could prevent OA disease progression. Skeletally mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) of their left femorotibial joints to induce joint degeneration typical of OA. Beginning 3 weeks post-operatively, and every three weeks thereafter for 12 weeks, either saline (1 mL) or sLN (100 µg in 1 mL saline) was injected intraarticularly into the operated knee. Six additional rabbits underwent sham surgery but without ACLT or post-operative injections. The effects on gross joint morphology and cartilage histologic changes were evaluated. In the Saline group, prominent erosion of articular cartilage occurred in both femoral condyle compartments and the lateral compartment of the tibial plateau while, sLN treatment reduced the severity of the cartilage damage in these compartments of the knee showing erosion. Furthermore, statistically significant differences were detected between the joint OA score of the saline and sLN treated groups (p = 0.0118). Therefore, periodic intraarticular injection of sLN is a promising nonsurgical treatment for preventing or retarding OA progression, by reducing cartilage degradation.
Asunto(s)
Proteínas de la Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/farmacología , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Proteoglicanos/metabolismo , Proteoglicanos/farmacología , Animales , Ligamento Cruzado Anterior/efectos de los fármacos , Ligamento Cruzado Anterior/metabolismo , Lesiones del Ligamento Cruzado Anterior/tratamiento farmacológico , Lesiones del Ligamento Cruzado Anterior/metabolismo , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Fémur/efectos de los fármacos , Fémur/metabolismo , Inyecciones Intraarticulares/métodos , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/metabolismo , Conejos , Tibia/efectos de los fármacos , Tibia/metabolismoRESUMEN
The cartilaginous endplates (CEPs) are thin layers of hyaline cartilage found adjacent to intervertebral discs (IVDs). In addition to providing structural support, CEPs regulate nutrient and metabolic exchange in the disc. In IVD pathogenesis, CEP undergoes degeneration and calcification, compromising nutrient availability and disc cell metabolism. The mechanism(s) underlying the biochemical changes of CEP in disc degeneration are currently unknown. Since calcification is often observed in later stages of IVD degeneration, we hypothesised that elevations in free calcium (Ca2+) impair CEP homeostasis. Indeed, our results demonstrated that the Ca2+ content was consistently higher in human CEP tissue with grade of disc degeneration. Increasing the levels of Ca2+ resulted in decreases in the secretion and accumulation of collagens type I, II and proteoglycan in cultured human CEP cells. Ca2+ exerted its effects on CEP matrix protein synthesis through activation of the extracellular calcium-sensing receptor (CaSR); however, aggrecan content was also affected independent of CaSR activation as increases in Ca2+ directly enhanced the activity of aggrecanases. Finally, supplementing Ca2+ in our IVD organ cultures was sufficient to induce degeneration and increase the mineralisation of CEP, and decrease the diffusion of glucose into the disc. Thus, any attempt to induce anabolic repair of the disc without addressing Ca2+ may be impaired, as the increased metabolic demand of IVD cells would be compromised by decreases in the permeability of the CEP.
Asunto(s)
Calcio/metabolismo , Cartílago/metabolismo , Cartílago/patología , Degeneración del Disco Intervertebral/patología , Disco Intervertebral/metabolismo , Disco Intervertebral/patología , Receptores Sensibles al Calcio/metabolismo , Agrecanos/metabolismo , Animales , Calcinosis/metabolismo , Calcinosis/patología , Bovinos , Condrocitos/metabolismo , Colágeno/metabolismo , Difusión , Matriz Extracelular/metabolismo , Técnicas de Silenciamiento del Gen , Glucosa/metabolismo , Humanos , Degeneración del Disco Intervertebral/metabolismo , Técnicas de Cultivo de Órganos , Proteoglicanos/metabolismo , ARN Interferente Pequeño/metabolismoRESUMEN
In degenerative intervertebral discs (IVD), type X collagen (COL X) expression (associated with hypertrophic differentiation) and calcification has been demonstrated. Suppression of COL X expression and calcification during disc degeneration can be therapeutic. In the present study we investigated the potential of human parathyroid hormone 1-34 (PTH) in suppressing indicators of calcification potential (alkaline phosphatase (ALP), Ca(2+), inorganic phosphate (Pi)), and COL X expression. Further, we sought to elucidate the mechanism of PTH action in annulus fibrosus (AF) and nucleus pulposus (NP) cells from human lumbar IVDs with moderate to advanced degeneration. Mitogen activated protein kinase (MAPK) signalling and alterations in the markers of calcification potential were analysed. PTH increased type II collagen (COL II) expression in AF (~200 %) and NP cells (~163 %) and decreased COL X levels both in AF and NP cells (~75 %). These changes in the expression of collagens were preceded by MAPK phosphorylation, which was increased in both AF and NP cells by PTH after 30 min. MAPK signalling inhibitor U0126 and protein kinase-A inhibitor H-89 DCH attenuated PTH stimulated COL II expression in both cell types. PTH decreased ALP activity and increased Ca(2+) release only in NP cells. The present study demonstrates that PTH can potentially retard IVD degeneration by stimulating matrix synthesis and suppressing markers of calcification potential in degenerated disc cells via both MAPK and PKA signalling pathways. Inhibition of further mineral deposition may therefore be a viable therapeutic option for improving the status of degenerating discs.
Asunto(s)
Calcificación Fisiológica/efectos de los fármacos , Disco Intervertebral/citología , Disco Intervertebral/efectos de los fármacos , Hormona Paratiroidea/farmacología , Adulto , Anciano , Fosfatasa Alcalina/metabolismo , Biomarcadores/metabolismo , Butadienos/farmacología , Calcio/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Disco Intervertebral/enzimología , Isoquinolinas/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Nitrilos/farmacología , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Factor de Transcripción SOX9/metabolismo , Sulfonamidas/farmacologíaRESUMEN
OBJECTIVE: Transforming growth factor-ß (TGF-ß) plays a critical role in cartilage homeostasis and deregulation of its signalling is implicated in osteoarthritis (OA). TGF-ß isoforms signal through a pair of transmembrane serine/threonine kinases known as the type I and type II TGF-ß receptors. Endoglin is a TGF-ß co-receptor that binds TGF-ß with high affinity in the presence of the type II TGF-ß receptor. We have previously shown that endoglin is expressed in human chondrocytes and that it forms a complex with the TGF-ß signalling receptors. However, the functional significance of endoglin expression in chondrocytes is unknown. Our objective was to determine whether endoglin regulates TGF-ß/Smad signalling and extracellular matrix (ECM) production in human chondrocytes and whether its expression varies with chondrocyte differentiation state. METHOD: Endoglin function was determined by overexpression or antisense morpholino/siRNA knockdown of endoglin in human chondrocytes and measuring TGF-ß-induced Smad phosphorylation, transcriptional activity and ECM production. Alterations in endoglin expression levels were determined during subculture-induced dedifferentiation of human chondrocytes and in normal vs OA cartilage samples. RESULTS: Endoglin enhances TGF-ß1-induced Smad1/5 phosphorylation and inhibits TGF-ß1-induced Smad2 phosphorylation, Smad3-driven transcriptional activity and ECM production in human chondrocytes. In addition, the enhancing effect of endoglin siRNA knockdown on TGF-ß1-induced Smad3-driven transcription is reversed by ALK1 overexpression. Furthermore, endoglin levels are increased in chondrocytes following subculture-induced dedifferentiation and in OA cartilage as compared to normal cartilage. CONCLUSION: Together, our results suggest that endoglin regulates the balance between TGF-ß/ALK1/Smad1/5 and ALK5/Smad2/3 signalling and ECM production in human chondrocytes and that endoglin may represent a marker for chondrocyte phenotype.
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Antígenos CD/metabolismo , Antígenos CD/farmacología , Condrocitos/metabolismo , Matriz Extracelular/metabolismo , Receptores de Superficie Celular/metabolismo , Proteínas Smad Reguladas por Receptores/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Western Blotting , Cartílago Articular/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Condrocitos/citología , Endoglina , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Osteoartritis/metabolismo , Fosforilación/efectos de los fármacosRESUMEN
Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration. Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing age; however, it increased significantly in the oldest group and in highly degenerate discs. We identified three matrix turnover phases. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity and a progressive reduction in denaturation of type 11 collagen. Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procollagen synthesis, both dependent on age and grade of tissue degeneration.
Asunto(s)
Envejecimiento , Proteínas de la Matriz Extracelular , Matriz Extracelular/metabolismo , Disco Intervertebral/fisiología , Adulto , Anciano , Agrecanos , Niño , Preescolar , Colágeno/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Lactante , Recién Nacido , Lectinas Tipo C , Región Lumbosacra , Persona de Mediana Edad , Procolágeno/metabolismo , Desnaturalización Proteica , Procesamiento Proteico-Postraduccional , Proteoglicanos/metabolismo , Agua/metabolismoRESUMEN
The functions of the intervertebral disc and of articular cartilage are intimately related to their aggrecan content. Aggrecan is a proteoglycan that interacts with hyaluronan to form large aggregates, which are responsible for the ability of the tissues to resist compressive loads. This function is related to the structure of aggrecan, and in particular to the large number of chondroitin sulphate chains present on its core protein. The chondroitin sulphate chains are present in two adjacent regions of the aggrecan core protein, termed the CS1 and CS2 domains. In the human, the region of the aggrecan gene encoding the CS1 domain exhibits size polymorphism, which can result in variation in the degree of chondroitin sulphate substitution of aggrecan in different individuals. This raises the possibility that the functional properties of aggrecan may vary between individuals, and that those individuals with an inferior aggrecan structure may be more susceptible to premature intervertebral disc or articular cartilage degeneration. Several studies have been performed to demonstrate such an association, but the results have been ambiguous. This review explains the relationship between aggrecan structure and function, describes the technique used to assess aggrecan polymorphism and the conclusions and limitations of the data obtained to date, and discusses the implications for tissue degeneration and clinical practice.
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Cartílago Articular/fisiopatología , Proteoglicanos Tipo Condroitín Sulfato/genética , Proteoglicanos Tipo Condroitín Sulfato/fisiología , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/fisiología , Disco Intervertebral/fisiopatología , Lectinas Tipo C/genética , Lectinas Tipo C/fisiología , Osteoartritis/fisiopatología , Polimorfismo Genético , Enfermedades de la Columna Vertebral/fisiopatología , Agrecanos , Alelos , Proteoglicanos Tipo Condroitín Sulfato/química , Sulfatos de Condroitina/fisiología , ADN/genética , Electroforesis en Gel de Agar , Proteínas de la Matriz Extracelular/química , Regulación de la Expresión Génica , Humanos , Ácido Hialurónico/fisiología , Lectinas Tipo C/química , Osteoartritis/etiología , Osteoartritis/genética , Reacción en Cadena de la Polimerasa , Estructura Terciaria de Proteína , Enfermedades de la Columna Vertebral/genéticaRESUMEN
A clinical strength MRI and intact bovine caudal intervertebral discs were used to test the hypotheses that (1) mechanical loading and trypsin treatment induce changes in NMR parameters, mechanical properties and biochemical contents; and (2) mechanical properties are quantitatively related to NMR parameters. MRI acquisitions, confined compression stress-relaxation experiments, and biochemical assays were applied to determine the NMR parameters (relaxation times T1 and T2, magnetization transfer ratio (MTR) and diffusion trace (TrD)), mechanical properties (compressive modulus H(A0) and hydraulic permeability k(0)), and biochemical contents (H(2)O, proteoglycan and total collagen) of nucleus pulposus tissue from bovine caudal discs subjected to one of two injections and one of two mechanical loading conditions. Significant correlations were found between k(0) and T1 (r=0.75,p=0.03), T2 (r=0.78, p=0.02), and TrD (r=0.85, p=0.007). A trend was found between H(A0) and TrD (r=0.56, p=0.12). However, loading decreased these correlations (r=0.4, p=0.2). The significant effect of trypsin treatment on mechanical properties, but not on NMR parameters, may suggest that mechanical properties are more sensitive to the structural changes induced by trypsin treatment. The significant effect of loading on T1 and T2, but not on H(A0) or k(0), may suggest that NMR parameters are more sensitive to the changes in water content enhanced by loading. We conclude that MRI offers promise as a sensitive and non-invasive technique for describing alterations in material properties of intervertebral disc nucleus, and our results demonstrate that the hydraulic permeability correlated more strongly to the quantitative NMR parameters than did the compressive modulus; however, more studies are necessary to more precisely characterize these relationships.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Interpretación de Imagen Asistida por Computador , Disco Intervertebral , Tripsina/química , Animales , Bovinos , Fuerza Compresiva , Difusión , Elasticidad , Disco Intervertebral/química , Disco Intervertebral/diagnóstico por imagen , Permeabilidad , Radiografía , Estrés Mecánico , Cola (estructura animal)/diagnóstico por imagenRESUMEN
Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio) in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.
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Matriz Extracelular/química , Cartílago Hialino/citología , Disco Intervertebral/citología , Ingeniería de Tejidos/métodos , Adolescente , Adulto , Anciano , Envejecimiento , Diferenciación Celular , Niño , Preescolar , Condrocitos/química , Condrocitos/citología , Colágeno/análisis , Glicosaminoglicanos/análisis , Humanos , Cartílago Hialino/química , Hidroxiprolina/análisis , Disco Intervertebral/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Persona de Mediana Edad , Fenotipo , Proteoglicanos/análisisRESUMEN
The purpose of this study was to determine whether a marker of bone resorption could be used noninvasively to diagnose and assess treatment of periprosthetic osteolysis. The crosslinked N-telopeptide marker of osteoclast-mediated bone resorption potentially has the sensitivity to detect periprosthetic osteolysis. Second-morning urine specimens were obtained from (a) seven age-matched controls, (b) eight patients who had a hip arthroplasty, hybrid implants at least 1 year after surgery, and no osteolysis, (c) 11 patients who had a hip arthroplasty and osteolysis, and (d) 10 patients who had a hip arthroplasty and with osteolysis before and after 6 weeks of oral Fosamax (alendronate) treatment. The Fosamax treatment consisted of one 10-mg dose per day for 6 weeks. Men and young women (less than 40 years old) were chosen for this study to avoid bone resorption enhanced after menopause as a possible confounder. An enzyme-linked immunosorbent assay technique for quantifying crosslinked N-telopeptides of type-I collagen was performed on all specimens. The patients with osteolysis had significantly elevated levels of N-telopeptide compared with the implant control group. In addition, levels of N-telopeptide were significantly lowered after Fosamax treatment. These findings indicate that a systemic bone-resorption marker (N-telopeptide) can be used to evaluate local particulate-induced osteolysis and its treatment. The study also provides clinical evidence that osteolysis is associated with increased osteoclast-mediated bone resorption and that this locally induced bone resorption can be suppressed by certain bisphosphonates (Fosamax). These insights have potential value in the understanding and clinical management of aseptic loosening.
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Colágeno/orina , Osteólisis/diagnóstico , Péptidos/orina , Adulto , Anciano , Alendronato/uso terapéutico , Biomarcadores , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/etiología , Creatinina/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteólisis/tratamiento farmacológicoRESUMEN
BACKGROUND: Posteroinferior instability of the shoulder has been associated with capsular laxity. The purposes of the present study were to describe the pathological morphology of the posteroinferior aspect of the glenolabral fossa in patients with primary posteroinferior instability and to prospectively examine the efficacy of managing this instability with use of an arthroscopic posteroinferior capsulolabral augmentation procedure. METHODS: Forty-one patients who had posteroinferior instability of the shoulder were managed with an arthroscopic shift of the posteroinferior aspect of the capsule to the adjacent labrum and were followed for a minimum of twelve months. Thirty-two patients had a primary procedure, and nine had a revision procedure. The mean duration of follow-up was twenty-eight months (range, twelve to sixty-nine months). All of the patients had presented with a symptomatic, positive finding on the jerk test and had participated in a minimum of six months of rehabilitation that had failed to relieve the symptoms. The patients were evaluated prospectively with a motion and stability examination and the Simple Shoulder Test. In addition, they completed the Short Form-36 Health Survey (SF-36) and a questionnaire on the outcome of treatment. RESULTS: Lesions affecting the posteroinferior aspect of the glenolabral concavity were seen in thirty-four patients (83 percent): five had labral detachment, seven had chondral or labral erosion, nine had capsular and synovial stripping, and thirteen had a labral split or tear. The mean score (and standard deviation) on the Simple Shoulder Test improved from 5.5 +/- 3.4 points to 8.1 +/- 3.3 points (p = 0.0023), and two of the eight SF-36 parameters improved significantly (p < 0.05). Conversely, nineteen patients who were receiving Workers' Compensation did not show any improvement in either of the two parameters. Thirty-five patients had improved stability of the shoulder, and the findings on all physical examinations had improved significantly (p < 0.0001). Twenty-eight patients had a perception of residual stiffness; this finding was in contrast to the mean score on the flexibility examination, which had not changed significantly at the time of the latest follow-up. CONCLUSIONS: Posteroinferior instability of the shoulder is associated not only with capsular laxity but also with well defined lesions of the glenolabral concavity. Arthroscopic capsulolabral augmentation to reduce posterior capsular laxity and to restore the depth of the glenolabral concavity has been shown to be effective treatment of this condition after a mean duration of follow-up of twenty-eight months.
Asunto(s)
Artroscopía/métodos , Inestabilidad de la Articulación/cirugía , Articulación del Hombro/cirugía , Adulto , Femenino , Estado de Salud , Humanos , Masculino , Satisfacción del Paciente , Estudios Prospectivos , Recuperación de la FunciónRESUMEN
STUDY DESIGN: We measured concentrations of specific molecules reflecting matrix synthesis and degradation in normal and scoliotic intervertebral discs and endplates. OBJECTIVES: The aim of this work was to quantitate markers of matrix turnover in normal versus adolescent idiopathic scoliotic intervertebral discs and cartilaginous endplates. SUMMARY OF BACKGROUND DATA: Changes in the intervertebral disc and endplate composition have been implicated as possible etiologic factors in the pathogenesis of adolescent idiopathic scoliosis. To better understand this process, it is important to compare the turnover of matrix components in scoliotic and normal intervertebral disc and endplate tissues. This comparison may help to improve our understanding of the role that disc and endplate tissues may play in the induction and/or progression of idiopathic scoliosis. METHODS: Fifteen scoliotic and 17 normal intervertebral discs and endplates were analyzed for their water, collagen, proteoglycan, and protein content. In addition, newly synthesized aggrecan and collagen Types I and II were measured. Percent total denatured collagen was also determined. RESULTS: The total collagen content was significantly lower in the scoliotic anulus and endplate regions, whereas glycosaminoglycan (GAG) content was significantly lower in the scoliotic endplates and nucleus regions. Conversely, total protein content was significantly higher in scoliotic endplates and elevated in scoliotic nucleus regions. Water content was significantly lower in the scoliotic anulus and endplate regions. When comparing the concave and convex regions of scoliotic endplates, there was no significant difference in concentration of any matrix component. The major difference in the synthetic marker levels relates to the synthesis of Type II collagen, which was higher in the nucleus, anulus, and endplate regions of scoliotic discs than in the corresponding regions of normal tissues. By contrast, the percent total denatured collagen was significantly elevated in the nucleus of normal tissues compared with the scoliotic ones. CONCLUSIONS: The higher collagen Type II synthetic levels and increased total protein content with no matrix turnover suggest that scoliotic changes are due to an altered and ineffective synthetic response to a pathologic mechanical environment.
Asunto(s)
Proteínas de la Matriz Extracelular , Matriz Extracelular/metabolismo , Disco Intervertebral/metabolismo , Placa Motora/metabolismo , Escoliosis/metabolismo , Adolescente , Agrecanos , Agua Corporal/metabolismo , Proteínas de Unión al Calcio/metabolismo , Colágeno/metabolismo , Colágeno Tipo II , Epítopos/metabolismo , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Lectinas Tipo C , Fragmentos de Péptidos/metabolismo , Procolágeno/metabolismo , Proteínas/metabolismo , Proteoglicanos/inmunología , Valores de ReferenciaRESUMEN
STUDY DESIGN: A direct method for three-dimensional in vivo spine kinematic studies was developed and used to measure segmental motion patterns in healthy subjects. OBJECTIVES: To validate the new method, and to study the L3-L4 segmental motion patterns for complex dynamic movements. SUMMARY OF BACKGROUND DATA: Conventional two-dimensional and three-dimensional radiographic methods have been used in the past to study spine kinematics. Few studies provided a direct approach to study segmental kinematics. No dynamic recordings of three-dimensional segmental motion patterns have been reported previously. METHODS: In 16 healthy men, Kirschner wires were inserted in the spinous processes of L3 and L4. Electromagnetic tracking sensors were attached to the pins. Motion data recorded during ranging exercises were used with biplanar radiographs to calculate L3-L4 segmental motion patterns. Errors resulting from pin deformation and the dynamic accuracy of the tracking system were investigated thoroughly. RESULTS: The average range of motion for flexion-extension was 16.9 degrees, for one side lateral bending 6.3 degrees and for one side axial rotation 1.1 degrees. Large intersubject variation was found in flexion-extension with values ranging from 7.1 to 29.9 degrees. Coupled motion patterns were found to be consistent among subjects in active lateral bending and inconsistent for active axial rotation. CONCLUSIONS: This new method offers dynamic recording capabilities and a measurement error comparable with stereo radiographic methods. Repetitive ranging experiments are highly reproducible. The range of motion for axial rotation seems overestimated in previous cadaveric studies. Coupling patterns show large variations between individuals.
Asunto(s)
Fenómenos Electromagnéticos/instrumentación , Vértebras Lumbares/fisiología , Rango del Movimiento Articular/fisiología , Diseño de Equipo , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Radiografía , Reproducibilidad de los ResultadosRESUMEN
STUDY DESIGN: The authors measured concentrations of specific molecules reflecting matrix synthesis and degradation in 121 human endplates and correlated them with aging and grade of degeneration. OBJECTIVES: Abnormal endplate development has been implicated in many spinal abnormalities, yet little is known about endplate matrix component turnover. SUMMARY OF BACKGROUND DATA: Techniques are available to perform an in situ investigation of matrix component turnover with aging and degeneration. METHODS: Newly synthesized aggrecan and Type I and Type II procollagens were measured with recently developed immunoassays. Percentage of denatured Type II collagen was assessed with a new enzyme-linked immunosorbent inhibition assay. RESULTS: Synthesis in endplates, measured by content of an aggrecan marker (846) and content of Types I and II procollagen markers (CPI and CPII), is highest in the neonatal and 2- to 5-year age groups and steadily diminishes with increasing age. However, in the oldest age group and in highly degenerated discs, the CPI epitope level increased significantly. Percentage of denatured Type II collagen, assessed by the presence of an epitope exposed with the cleavage of Type II collagen, increased from the neonatal to the 2- to 5-year age groups. The percentage progressively decreased with increasing age. However, it significantly increased in endplates from highly degenerated discs. CONCLUSIONS: The authors identified three matrix turnover phases, related to age and grade of degeneration. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of Type II collagen. Phase II (aging and maturation) is distinguished by a drop in synthetic activity and a reduction in denaturation of Type II collagen. Phase III (degenerative) is illustrated by an increase in Type II collagen denaturation and Type I procollagen synthesis, both related to grade of tissue degeneration.
Asunto(s)
Envejecimiento/metabolismo , Proteínas de la Matriz Extracelular , Matriz Extracelular/metabolismo , Disco Intervertebral/crecimiento & desarrollo , Disco Intervertebral/metabolismo , Región Lumbosacra/fisiología , Adolescente , Adulto , Anciano , Agrecanos , Niño , Preescolar , Proteoglicanos Tipo Condroitín Sulfato/análisis , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Colágeno/análisis , Colágeno/metabolismo , Epítopos/análisis , Femenino , Glicosaminoglicanos/análisis , Glicosaminoglicanos/metabolismo , Humanos , Lactante , Recién Nacido , Disco Intervertebral/química , Lectinas Tipo C , Persona de Mediana Edad , Degeneración Nerviosa , Embarazo , Procolágeno/análisis , Procolágeno/metabolismo , Desnaturalización Proteica , Proteoglicanos/análisis , Proteoglicanos/metabolismo , Agua/análisis , Agua/metabolismoRESUMEN
Posterior shoulder instability is a pathology that is increasingly seen in athletes. Excessive capsular laxity was originally proposed as the key component. Recent cadaveric and arthroscopic work has identified the importance of glenolabral integrity and glenoid depth in maintaining glenohumeral stability. Arthroscopic techniques to treat posterior instability are emerging. Until recently, reports of arthroscopic reconstruction focused entirely on capsular glenohumeral stability by altering two separate mechanisms: deepening of the glenoid concavity and reducing the capsular joint volume. This is accomplished by shifting the capsule to buttress the glenoid labrum. Thus increasing capsular tension increases the resultant compressive force vector into a deepened glenolabral concavity that, when combined together, enhances glenohumeral stability. In clinical and laboratory settings, we have shown that posteroinferior shoulder instability is associated with both capsular laxity and well-defined pathological lesions of the glenolabral concavity. Our results indicate that arthroscopic posterior capsulolabral repair and augmentation is a useful tool to restore the depth of the glenolabral concavity and to reduce the redundant posteroinferior capsule. This technique is effective in treating posteroinferior instability.
Asunto(s)
Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/terapia , Lesiones del Hombro , Adulto , Artroscopía , Fenómenos Biomecánicos , Terapia Combinada , Terapia por Ejercicio , Femenino , Estudios de Seguimiento , Humanos , Inestabilidad de la Articulación/clasificación , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/fisiopatología , Masculino , Anamnesis , Examen Físico , Rango del Movimiento Articular , Recurrencia , Factores de Riesgo , Rotación , Técnicas de Sutura , Resultado del TratamientoRESUMEN
Posterior shoulder instability is associated with capsular laxity and well-defined pathologic lesions of the gleno-labral concavity. Most arthroscopic techniques have concentrated on capsular shift or plication of capsular laxity. This article demonstrates that arthroscopic capsulolabral plication simultaneously can augment the glenolabral concavity to restore the glenoid depth, and can reduce excessive capsular laxity of the redundant posteroinferior capsule. This method has proven effective in treating posterior instability.
Asunto(s)
Artroscopía/métodos , Cápsula Articular/cirugía , Articulación del Hombro/cirugía , Cadáver , Humanos , Húmero/patología , Húmero/cirugía , Cápsula Articular/patología , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/cirugía , Articulación del Hombro/patologíaRESUMEN
A septic loosening and osteolysis can compromise the available host bone in patients requiring revision hip arthroplasty. Secure fixation of revision femoral components may not be possible if reliant only on proximal femoral bone for biologic fixation or cement interdigitation. The challenge for the revision arthroplasty surgeon is to find the best method to secure the implant in a femur with deficient bone proximally that will provide stability for load bearing and motion. In addition to providing stability, the implant must be durable and maintain long-term fixation. With over 16 years of experience with fully porous coated femoral revision implants, we have found that maximizing prosthetic-bone fit in the proximal femoral diaphyseal bone provides reliable long-term fixation in the majority of femoral revision cases.