RESUMEN
BACKGROUND: Anterior cruciate ligament transection surgery (ACLT)-induced OA model was often used to investigate the molecular mechanism of knee osteoarthritis (KOA). Researches have shown that vascular endothelial growth factor (VEGF) played an important role in OA. The present study aimed to investigate the pathological changes after ACLT surgery and reveal the expression characteristics of the VEGF-A/VEGFR2 signaling pathway in this model. METHODS: Moderate KOA model was established by ACLT, and 1, 2, 4, 8, and 12 weeks after surgery, hematoxylin-eosin (HE) and Safranin-O(S-O) staining were used to detect the pathological changes in mouse knee cartilage, and the matrix biomarkers A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5(ADAMTS5), Collagen II (COL-II) were detected using immunohistochemistry (IHC), CD31 was detected by immunofluorescence (IF) to show the vascular invasion in cartilage, and proteins expression of VEGF-A pathway were detected by Western blot (WB). Meanwhile, the inflammatory biomarkers cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cartilage were detected by WB. RESULTS: ACLT surgery can lead to degeneration of cartilage in mice, and the characteristics of the lesion were time-dependent. The ADAMTS5-positive cells increased while COL-II decreased in OA cartilage with time, and new blood vessels labeled by CD31 can be seen from 1 week in OA cartilage, and increased in 8 and 12 weeks. The expression of VEGF-A, VEGFR2, COX-2, and iNOS were higher than control groups, which were basically consistent with the degree of osteoarthritis. CONCLUSIONS: The degenerative degree of articular cartilage was time-dependent; angiogenesis and inflammation were important pathological changes of cartilage in KOA. The expression of the VEGF-A/VEGFR2 signaling pathway was basically correlated with the degree of KOA.
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Ligamento Cruzado Anterior/cirugía , Cartílago Articular/metabolismo , Cartílago Articular/patología , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/metabolismo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Cartílago Articular/irrigación sanguínea , Modelos Animales de Enfermedad , Femenino , Inflamación , Masculino , Ratones Endogámicos C57BL , Neovascularización Patológica , Osteoartritis de la Rodilla/patología , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/fisiología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA. METHODS: A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations. RESULTS: Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral ß -6.23, medial ß -5.14, total ß -11.35 mm3/mmHg; diastolic: lateral ß -10.25, medial ß -11.29, total ß -21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral ß -17.35, total ß -28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume; however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial ß -8.24, total ß -19.13 mm3/%; femoral: lateral ß -23.70, medial ß -26.42, total ß -50.12 mm3/%). CONCLUSIONS: Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.
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Presión Sanguínea , Cartílago Articular/patología , Articulación de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Rigidez Vascular , Cartílago Articular/irrigación sanguínea , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Articulación de la Rodilla/irrigación sanguínea , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/patología , Análisis de la Onda del Pulso , Ensayos Clínicos Controlados Aleatorios como Asunto , Tibia/irrigación sanguínea , Tibia/patologíaRESUMEN
BACKGROUND: Meniscal vascular supply is an important determinant of its healing potential. It has been reported that only the peripheral 30% of the meniscus is vascularized in cadavers aged 53 to 94 years; however, the vascularity in young patients, in whom meniscal repair is more often performed, is unknown. PURPOSE: The primary objective was to analyze and measure the microvascular anatomy of the meniscus in adult cadaveric specimens <35 years old. The secondary objective was to assess angiogenic potential by quantifying regional gene expression in a meniscal allograft cohort <45 years old. STUDY DESIGN: Descriptive laboratory study. METHODS: In part 1 of this study, 13 fresh-frozen cadaveric knees (age range, 22-34 years; mean, 28.5 years) underwent popliteal artery India ink injection and tissue clearing using a Spalteholz technique, followed by microvascular vascular measurement. In part 2, mRNA was isolated from 13 meniscal allografts (age range, 17-43 years; mean, 27.2 years), and expression of angiogenic genes, vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 1 (FLT1) was quantified using real-time polymerase chain reaction. RESULTS: The maximal depth of vascular penetration into the periphery of the medial and lateral menisci ranged from 0% to 42% and 0% to 48%, respectively. There was variation in the degree of vascular penetration within the medial meniscus, with the posterior horn having a significantly smaller depth of penetration (median, 8.7%) than that of the anterior horn (median, 17.4%; P < .0001) or midbody (median, 17.5%; P = .0003). There were no differences in angiogenesis gene expression (VEGF/FLT1) based on circumferential or radial meniscal locations. CONCLUSION: The vascular supply of the medial and lateral menisci in specimens from adults <35 years of age extended farther than what was reported in specimens from older individuals; however, median values remained consistent. Gene expression of the angiogenic marker VEGF was low throughout all regions of uninjured menisci from young adults, which is consistent with reports in older specimens. CLINICAL RELEVANCE: Improved understanding of meniscal vascular supply in young adults is critical to informing clinical treatment decisions.
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Meniscos Tibiales/irrigación sanguínea , Microcirculación , Factor A de Crecimiento Endotelial Vascular , Adolescente , Adulto , Artroplastia de Reemplazo de Rodilla , Cartílago Articular/irrigación sanguínea , Humanos , Meniscos Tibiales/cirugía , Trasplante Homólogo , Factor A de Crecimiento Endotelial Vascular/genética , Cicatrización de Heridas , Adulto JovenRESUMEN
Injection with monosodium iodoacetate (MIA) is widely used to produce osteoarthritis (OA). Ultrathin sheet plastination has been used to study the morphology of structures, with strong application in anatomical education and research. Our aim was to carry out, for the first time, ultrathin sheet plastination of rat humeral joints to observe the neovascularization provoked by OA. We injected 0.1 mL of MIA into the left humeral joints of ten Sprague-Dawley rats. The right shoulders of the same rats were used as control. Sixteen weeks after the injection, the animals were euthanized and were given an immediate red epoxy resin injection through the thoracic aorta. The samples were fixed in 10% formalin, prior to the plastination process, without decalcification. Samples were dehydrated with acetone (100%) at - 25 °C, for 10 days. Later, for degreasing, samples were immersed in methylene chloride at room temperature during 1 week. Forced impregnation was performed inside a stove within a vacuum chamber. The plastinated blocks obtained were cut with a slow velocity diamond blade saw. Slices were placed in curing chambers to achieve curing and final tissue transparentation. 230 µm thickness slices were obtained. The slices were analyzed under magnifying glass and microscope, achieving visualization of OA neovascularization. The cartilage affected by OA loses its ability to remain avascular, and blood vessels invade it from the subchondral bone to the calcified and uncalcified cartilage. Ultra-thin sheet plastination is useful to observe articular cartilage neovascularization, caused by OA induced with MIA in humeral rat joint.
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Cartílago Articular/irrigación sanguínea , Húmero , Articulaciones , Neovascularización Fisiológica/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Plastinación/métodos , Animales , Inyecciones Intraarticulares , Ácido Yodoacético , Ratas Sprague-DawleyRESUMEN
Articular osteochondrosis (OC) arises due to vascular failure and ischemic chondronecrosis. The aim of the study was to describe the histological and computed tomographic (CT) characteristics of changes in the distal femoral physis of pigs, to determine if they represented OC lesions and if the pathogenesis was the same as for articular OC. The material included 19 male Landrace pigs bred for predisposition to OC. One or 2 pigs were euthanized and CT-scanned at 2-week intervals from 82 to 180 days of age. Material from 10 pigs was available for histological validation. The CT scans revealed 31 lesions confirmed in 3 planes and 1 additional macroscopically visible lesion confirmed in 2 CT planes. Twelve of the lesions were histologically validated. All lesions were compatible with OC. Cartilage canal and eosinophilic streak morphological changes corresponded to failure of end arteries coursing from the epiphysis, toward the metaphysis. The location of lesions was compatible with failure at the point of vessel incorporation into bone. Vascular failure was associated with retention of viable hypertrophic chondrocytes and delayed ossification but not cartilage necrosis. Lesion width ranged from 1.1% to 45.6% of the physis. Several lesions were expected to resolve due to small size and evidence of CT-identifiable, reparative ossification. Angular limb deformity was not detected in any pig. The pathogenesis of physeal OC started with vascular failure that was morphologically identical to articular OC. The heritable predisposition may therefore be the same. The association between lesions and limb deformity should be studied further in older pigs in future.
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Cartílago Articular/irrigación sanguínea , Placa de Crecimiento/irrigación sanguínea , Osteocondrosis/veterinaria , Enfermedades de los Porcinos/patología , Animales , Huesos/patología , Cartílago Articular/patología , Fémur/patología , Placa de Crecimiento/patología , Masculino , Osteocondrosis/patología , Porcinos , Enfermedades de los Porcinos/etiologíaRESUMEN
CD271 is a marker of bone marrow MSCs with enhanced differentiation capacity for bone or cartilage repair. However, the nature of CD271+ MSCs from adipose tissue (AT) is less well understood. Here, we investigated the differentiation, wound healing and angiogenic capacity of plastic adherent MSCs (PA MSCs) versus CD271+ MSCs from AT. There was no difference in the extent to which PA MSCs and CD271+ MSCs formed osteoblasts, adipocytes or chondrocytes in vitro. In contrast, CD271+ MSCs transplanted into athymic rats significantly enhanced osteochondral wound healing with reduced vascularisation in the repair tissue compared to PA MSCs and control animals; there was little histological evidence of mature articular cartilage formation in all animals. Conditioned medium from CD271+ MSC cultures was less angiogenic than PA MSC conditioned medium, and had little effect on endothelial cell migration or endothelial tubule formation in vitro. The low angiogenic activity of CD271+ MSCs and improved early stage tissue repair of osteochondral lesions when transplanted, along with a comparable differentiation capacity along mesenchymal lineages when induced, suggests that these selected cells are a better candidate than PA MSCs for the repair of cartilaginous tissue.
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Condrogénesis , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Cicatrización de Heridas , Animales , Cartílago Articular/irrigación sanguínea , Diferenciación Celular , Células Cultivadas , Femenino , Humanos , Neovascularización Patológica , Proteínas del Tejido Nervioso/metabolismo , Ratas , Ratas Desnudas , Receptores de Factor de Crecimiento Nervioso/metabolismoRESUMEN
As a stimulating point in acupuncture, acupoint has unique microcirculatory features, and its dynamics vary greatly depending on health status. Acupoint sensitization is defined as the transformation of an acupoint from a "silenced status" (healthy) to an "activated status" (disease). Our previous study demonstrated that acupoint sensitization is associated with an increase in the level of local blood perfusion. However, the structural changes in microcirculation during acupoint sensitization have yet to be elucidated because the high-resolution microcirculation imaging of acupoints has been difficult to obtain. In this study, the structural changes in microcirculation at the Zusanli (ST36), Yanglingquan (GB34) and nonacupoint sites on days 0, 7 and 21 were dynamically observed during acupoint sensitization in an experimental knee osteoarthritis mouse model by using optical-resolution photoacoustic microscopy. The results showed that no significant differences in microvessel density, the distribution of vessel diameters or vascular tortuosity were observed at the GB34, ST36 or nonacupoint sites among days 0, 7 and 21. We proposed that acupoint sensitization may not be associated with the structural changes in microcirculation and that the microcirculatory changes during acupoint sensitization are more likely to be functional. The functional characteristics of the sensitized acupoints warrant further investigation.
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Puntos de Acupuntura , Microvasos/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/terapia , Animales , Cartílago Articular/irrigación sanguínea , Modelos Animales de Enfermedad , Masculino , Ratones , Proyectos PilotoRESUMEN
OBJECTIVE: Juvenile osteochondritis dissecans (JOCD) is similar to osteochondrosis dissecans (OCD) in animals, which is the result of failure of the cartilage canal blood supply, ischemic chondronecrosis and delayed ossification, or osteochondrosis. The aim of the current study was to determine if osteochondrosis lesions occur at predilection sites for JOCD in children. METHOD: Computed tomographic (CT) scans of 23 knees (13 right, 10 left) from 13 children (9 male, 4 female; 1 month to 11 years old) were evaluated for lesions consisting of focal, sharply demarcated, uniformly hypodense defects in the ossification front. Histological validation was performed in 11 lesions from eight femurs. RESULTS: Thirty-two lesions consisting of focal, uniformly hypodense defects in the ossification front were identified in the CT scans of 14 human femurs (7 left, 7 right; male, 7-11 years old). Defects corresponded to areas of ischemic chondronecrosis in sections from all 11 histologically validated lesions. Intra-cartilaginous secondary responses comprising proliferation of adjacent chondrocytes and vessels were detected in six and two lesions, whereas intra-osseous responses including accumulation of chondroclasts and formation of granulation tissue occurred in 10 and six lesions, respectively. One CT cyst-like lesion contained both a pseudocyst and a true cyst in histological sections. CONCLUSION: Changes identical to osteochondrosis in animals were detected at predilection sites for JOCD in children, and confirmed to represent failure of the cartilage canal blood supply and ischemic chondronecrosis in histological sections.
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Cartílago Articular/irrigación sanguínea , Isquemia/complicaciones , Articulación de la Rodilla/irrigación sanguínea , Osteocondritis Disecante/etiología , Osteocondrosis/complicaciones , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Niño , Preescolar , Condrocitos/patología , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Humanos , Lactante , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Osteocondritis Disecante/diagnóstico por imagen , Osteocondritis Disecante/patología , Osteocondrosis/diagnóstico por imagen , Osteocondrosis/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVES: The metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints may be involved in juvenile idiopathic arthritis. Our goal was to describe their normal sonoanatomy in healthy children, according to age and gender. METHODS: We studied 41 consecutive healthy children (20 girls, 21 boys; age 2-15 years) divided into four age groups: 2-4 years (n=9), 5-7 years (n=11), 8-12 years (n=12), and 13-15 years (n=9). Longitudinal ultrasound axis of the MCP and MTP joints were obtained. The evolution of the cartilage thickness and vascularisation of these joints were studied according to age and gender. The MCP or MTP joints were the statistical unit. RESULTS: At all sites, on B-mode images, cartilage thickness was associated with age (p<0.0001). Cartilage thickness at different sites was significantly greater in boys than in girls (p≤0.05). Blood vessels were seen within the cartilage, with differences across age groups. CONCLUSIONS: This study provides children's age- and gender-specific sonoanatomy data of MCP and MTP and confirms the importance of using colour Doppler or Power Doppler to study cartilage vascularisation.
Asunto(s)
Cartílago Articular/irrigación sanguínea , Cartílago Articular/diagnóstico por imagen , Articulación Metacarpofalángica/irrigación sanguínea , Articulación Metacarpofalángica/diagnóstico por imagen , Articulación Metatarsofalángica/irrigación sanguínea , Articulación Metatarsofalángica/diagnóstico por imagen , Neovascularización Fisiológica , Ultrasonografía Doppler , Adolescente , Desarrollo del Adolescente , Factores de Edad , Cartílago Articular/crecimiento & desarrollo , Niño , Desarrollo Infantil , Preescolar , Femenino , Humanos , Masculino , Articulación Metacarpofalángica/crecimiento & desarrollo , Articulación Metatarsofalángica/crecimiento & desarrollo , Valor Predictivo de las Pruebas , Valores de Referencia , Estudios Retrospectivos , Factores SexualesRESUMEN
The control of the different angiogenic process is an important point in osteochondral regeneration. Angiogenesis is a prerequisite for osteogenesis in vivo; insufficient neovascularization of bone constructs after scaffold implantation resulted in hypoxia and cellular necrosis. Otherwise, angiogenesis must be avoided in chondrogenesis; vascularization of the cartilage contributes to structural damage and pain. Finding a balance between these processes is important to design a successful treatment for osteochondral regeneration. This chapter shows the most important advances in the control of angiogenic process for the treatment of osteochondral diseases focused on the administration of pro- or anti-angiogenic factor and the design of the scaffold.
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Huesos/irrigación sanguínea , Cartílago Articular/irrigación sanguínea , Neovascularización Fisiológica , Andamios del Tejido , Inhibidores de la Angiogénesis/uso terapéutico , Moduladores de la Angiogénesis/uso terapéutico , Enfermedades Óseas/fisiopatología , Enfermedades Óseas/cirugía , Enfermedades de los Cartílagos/fisiopatología , Enfermedades de los Cartílagos/cirugía , Cationes/uso terapéutico , Condrogénesis/fisiología , Predicción , Humanos , Neovascularización Patológica/prevención & control , Osteogénesis/fisiología , Complicaciones Posoperatorias/prevención & control , Andamios del Tejido/clasificaciónRESUMEN
OBJECTIVES: To evaluate the clinical feasibility of ultrahigh field 7-T SWI to visualize vessels and assess their density in the immature epiphyseal cartilage of human knee joints. METHODS: 7-T SWI of 12 knees (six healthy volunteers, six patients with osteochondral abnormalities; mean age 10.7 years; 3 female, 9 male) were analysed by two readers, classifying intracartilaginous vessel densities (IVD) in three grades (no vessels, low IVD and high IVD) in defined femoral, tibial and patellar zones. Differences between patients and volunteers, IVDs in different anatomic locations, differences between cartilage overlying osteochondral abnormalities and corresponding normal zones, and differences in age groups were analysed. RESULTS: Interrater reliability showed moderate agreement between the two readers (κ = 0.58, p < 0.001). The comparison of IVDs between patients and volunteers revealed no significant difference (p = 0.706). The difference between zones in the cartilage overlying osteochondral abnormalities to corresponding normal zones showed no significant difference (p = 0.564). IVDs were related to anatomic location, with decreased IVDs in loading areas (p = 0.003). IVD was age dependent, with more vessels present in the younger participants (p = 0.001). CONCLUSIONS: The use of SWI in conjunction with ultrahigh field MRI makes the in vivo visualization of vessels in the growing cartilage of humans feasible, providing insights into the role of the vessel network in acquired disturbances. KEY POINTS: ⢠SWI facilitates in vivo visualization of vessels in the growing human cartilage. ⢠Interrater reliability of the intracartilaginous vessel grading was moderate. ⢠Intracartilaginous vessel densities are dependent on anatomical location and age.
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Placa de Crecimiento/irrigación sanguínea , Placa de Crecimiento/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Osteocondritis Disecante/diagnóstico por imagen , Adolescente , Cartílago Articular/irrigación sanguínea , Cartílago Articular/diagnóstico por imagen , Niño , Estudios de Factibilidad , Femenino , Humanos , Articulación de la Rodilla/irrigación sanguínea , Masculino , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Extensive osteochondritis dissecans (OCD) lesions of the lateral ridge of the trochlea of the femur (LRTF), the most common OCD-affected site in the stifle, have a poor outcome with surgical debridement and can be career ending. The early detection of osteochondrosis lesions and their conservative management holds the promise to enhance outcome. We hypothesise that ultrasonography is a valuable field screening tool to detect and monitor early subclinical LRTF osteochondrosis. OBJECTIVES: The goals were to 1) describe the normal ultrasonographic features of the LRTF in foals of different ages and 2) screen a foal cohort at the farm for early subclinical osteochondrosis lesions. STUDY DESIGN: Prospective cohort study. METHODS: The LRTF of both hindlimbs of Thoroughbred foals (n = 46, 27-166 days old) were imaged once with ultrasonography and radiography (lateromedial and caudolateral-craniomedial oblique views). Cartilage thickness, ossification front indentation of the chondro-osseous junction and epiphyseal vascularisation were assessed on ultrasonography. Follow-up radiographs were taken as yearlings. RESULTS: The cartilage thickness, ossification front indentation and epiphyseal vascularisation significantly decreased with advancing maturity. Subclinical osteochondrosis lesions, characterised by semicircular indentations in the ossification front (indirect evidence of focal failure of ossification and retained cartilage) were detected in six foals (28-145 days old), both with radiography and ultrasonography. Ultrasonography provided a better overall subjective assessment of the osteochondrosis lesion topography (length, depth and the width) compared with radiography. MAIN LIMITATIONS: Post-mortem validation of lesions was not possible. CONCLUSION: Ultrasonography of the LRTF is a practical, inexpensive and reliable technique to discriminate physiological from pathological events at the LRTF in young foals. It revealed the complex topography of the chondro-osseous junction permitting a rapid, comprehensive assessment of the subclinical osteochondrosis lesions in very young foals.
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Miembro Posterior/diagnóstico por imagen , Enfermedades de los Caballos/diagnóstico por imagen , Osteocondrosis/veterinaria , Envejecimiento , Animales , Cartílago Articular/irrigación sanguínea , Cartílago Articular/patología , Epífisis/irrigación sanguínea , Epífisis/diagnóstico por imagen , Femenino , Caballos , Masculino , Osteocondrosis/diagnóstico por imagen , Estudios ProspectivosRESUMEN
Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients.
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Trasplante de Médula Ósea , Cartílago Articular/metabolismo , Condrocitos/trasplante , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Trasplante de Células Madre Mesenquimatosas , Osteoartritis de la Rodilla/terapia , Anciano , Animales , Cartílago Articular/irrigación sanguínea , Cartílago Articular/patología , Cartílago Articular/fisiología , Diferenciación Celular , Células Cultivadas , Condrocitos/metabolismo , Condrocitos/patología , Técnicas de Cocultivo , Humanos , Hipertrofia/metabolismo , Hipertrofia/patología , Hipertrofia/prevención & control , Masculino , Ratones Endogámicos NOD , Ratones SCID , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Neovascularización Patológica/prevención & control , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Prueba de Estudio Conceptual , Ratas Wistar , Regeneración , Trasplante HeterólogoRESUMEN
Osteoarthritis is characterized by a chronic, progressive and irreversible degradation of the articular cartilage associated with joint inflammation and a reparative bone response. More than 100 million people are affected by this condition worldwide with significant health and welfare costs. Our available treatment options in osteoarthritis are extremely limited. Chondral or osteochondral grafts have shown some promising results but joint replacement surgery is by far the most common therapeutic approach. The difficulty lies on the limited regeneration capacity of the articular cartilage, poor blood supply and the paucity of resident progenitor stem cells. In addition, our poor understanding of the molecular signalling pathways involved in the senescence and apoptosis of chondrocytes is a major factor restricting further progress in the area. This review focuses on molecules and approaches that can be implemented to delay or even rescue chondrocyte apoptosis. Ways of modulating the physiologic response to trauma preventing chondrocyte death are proposed. The use of several cytokines, growth factors and advances made in altering several of the degenerative genetic pathways involved in chondrocyte apoptosis and degradation are also presented. The suggested approaches can help clinicians to improve cartilage tissue regeneration.
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Apoptosis , Cartílago Articular/citología , Condrocitos/metabolismo , Condrogénesis/fisiología , Osteoartritis/fisiopatología , Ingeniería de Tejidos , Animales , Cartílago Articular/irrigación sanguínea , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Osteoartritis/complicaciones , Transducción de SeñalRESUMEN
BACKGROUND: Articular osteochondrosis is a common cause of leg weakness in pigs and is defined as a focal delay in the endochondral ossification of the epiphysis. The first demonstrated steps in the pathogenesis consist of loss of blood supply and subsequent chondronecrosis in the epiphyseal growth cartilage. Blood vessels in cartilage are located in cartilage canals and become incorporated into the secondary ossification centre during growth. It has been hypothesized that vascular failure occurs during this incorporation process, but it is not known what predisposes a canal to fail. To obtain new information that may reveal the cause of vascular failure, the distal femur of 4 pigs aged 82-140 days was sampled and examined by non-linear optical microscopy. This novel technique was used for its ability to reveal information about collagen by second harmonic generation and cellular morphology by two-photon-excited fluorescence in thick sections without staining. The aims were to identify morphological variations between cartilage canal segments and to examine if failed cartilage canals could be followed back to the location where the blood supply ceased. RESULTS: The cartilage canals were shown to vary in their content of collagen fibres (112/412 segments), and the second harmonic and fluorescence signals indicated a variation in the bundling of collagen fibrils (245/412 segments) and in the calcification (30/412 segments) of the adjacent cartilage matrix. Failed cartilage canals associated with chondronecrosis were shown to enter the epiphyseal growth cartilage from not only the secondary ossification centre, but also the attachment site of the caudal cruciate ligament. CONCLUSION: The variations between cartilage canal segments could potentially explain why the blood supply fails at the osteochondral junction in only a subset of the canals. Proteins linked to these variations should be examined in future genomic studies. Although incorporation can still be a major cause, it could not account for all cases of vascular failure. The role of the caudal cruciate ligament in the cause of osteochondrosis should therefore be investigated further.
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Cartílago Articular/patología , Fémur/patología , Microscopía Fluorescente/veterinaria , Osteocondrosis/veterinaria , Animales , Cartílago Articular/irrigación sanguínea , Cartílago Articular/diagnóstico por imagen , Fémur/irrigación sanguínea , Fémur/diagnóstico por imagen , Masculino , Microscopía Fluorescente/métodos , Microscopía de Fluorescencia por Excitación Multifotónica/veterinaria , Osteocondrosis/diagnóstico por imagen , Osteocondrosis/patología , PorcinosRESUMEN
PURPOSE OF REVIEW: This review describes the contributions of abnormal bone circulation to the pathophysiology of osteoarthritis. Combining dynamic imaging with MRI and PET with previous observations reveals that venous stasis and a venous outlet syndrome is most likely the key circulatory pathology associated with the initiation or progression of osteoarthritis. RECENT FINDINGS: MRI and PET have revealed that venous outflow obstruction results in physicochemical changes in subchondral bone to which osteoblasts are responsive. The osteoblasts express an altered pattern of cytokines, many of which can serve as structural or signaling molecules contributing to both bone remodeling and cartilage degeneration. The patterns of circulatory changes are associated with alterations in the physicochemical environment of subchondral bone, including hypoxia. Osteoblast cytokines can transit the subchondral bone plate and calcified cartilage and communicate with chondrocytes.
Asunto(s)
Huesos/irrigación sanguínea , Cartílago Articular/irrigación sanguínea , Hemodinámica/fisiología , Osteoartritis/etiología , Remodelación Ósea/fisiología , Huesos/diagnóstico por imagen , Huesos/fisiopatología , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/fisiopatología , Condrocitos/fisiología , Humanos , Osteoartritis/diagnóstico por imagen , Osteoartritis/fisiopatología , Flujo Sanguíneo Regional/fisiologíaRESUMEN
OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.
Asunto(s)
Cartílago Articular/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Flujo Sanguíneo Regional , Insuficiencia Renal Crónica/diagnóstico por imagen , Animales , Cartílago Articular/irrigación sanguínea , Modelos Animales de Enfermedad , Articulación de la Rodilla/irrigación sanguínea , Imagen por Resonancia Magnética , Masculino , Nefrectomía , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The vascular supply to the acetabular labrum is important in the treatment of labral lesions. However, in vivo blood flow measurements in the acetabular labrum have not been described in the literature. The purpose of this study was to examine this blood flow in vivo using laser Doppler flowmetry (LDF) in patients with acetabular dysplasia. METHODS: Periacetabular osteotomy combined with arthroscopy was performed in 47 consecutive patients (three males, 44 females; mean age at surgery, 35.6 years; range, 15-60 years). In all patients, blood flow in the acetabular labrum was measured with LDF during arthroscopy. The acetabular labral lesions were categorized according to the modified Beck classification: detachment and full-thickness labral tears were assigned to the T group and normal labrum to the N group. Blood flow rates in the acetabular labrum were compared between the T and N groups. The associations between labral blood flow and the lateral center-edge angle (CEa) and patient age were also evaluated. RESULTS: The T and N groups comprised 31 and 16 patients, respectively. The mean blood flow rate was 1.94 ± 0.41 ml/min/100 g in the T group and 1.94 ± 0.34 ml/min/100 g in the N group, with no significant difference between the groups (P = 0.884). No association was noted between blood flow and either the CEa or patient age (ß = -0.018, P = 0.077 and ß = -0.001, P = 0.770, respectively). CONCLUSIONS: On LDF, blood flow in the acetabular labrum was present in all patients, regardless of the severity of acetabular labral tears, CEa, or age.
Asunto(s)
Acetábulo/irrigación sanguínea , Cartílago Articular/irrigación sanguínea , Luxación Congénita de la Cadera/cirugía , Acetábulo/cirugía , Adolescente , Adulto , Artroscopía/métodos , Cartílago Articular/lesiones , Cartílago Articular/cirugía , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Flujometría por Láser-Doppler/métodos , Masculino , Persona de Mediana Edad , Osteotomía/métodos , Flujo Sanguíneo Regional , Adulto JovenRESUMEN
Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.
Asunto(s)
Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Cartílago Articular/patología , Inflamación/patología , Articulaciones/patología , Prolactina/inmunología , Inhibidores de la Angiogénesis/inmunología , Animales , Artritis Reumatoide/epidemiología , Artritis Reumatoide/fisiopatología , Cartílago Articular/irrigación sanguínea , Cartílago Articular/inmunología , Cartílago Articular/fisiopatología , Femenino , Humanos , Tolerancia Inmunológica , Inmunidad Celular , Inflamación/epidemiología , Inflamación/inmunología , Inflamación/fisiopatología , Articulaciones/irrigación sanguínea , Articulaciones/inmunología , Articulaciones/fisiopatología , Masculino , Reproducción , Factores Sexuales , Estrés Fisiológico , Estrés PsicológicoRESUMEN
Cartilage canals have been shown to contain discontinuous blood vessels that enable circulating bacteria to bind to cartilage matrix, leading to vascular occlusion and associated pathological changes in pigs and chickens. It is also inconsistently reported that cartilage canals are surrounded by a cellular or acellular wall that may influence whether bacterial binding can occur. It is not known whether equine cartilage canals contain discontinuous endothelium or are surrounded by a wall. This study aimed to examine whether there were discontinuities in the endothelium of cartilage canal vessels, and whether canals had a cellular or acellular wall, in the epiphyseal growth cartilage of foals. Epiphyseal growth cartilage from the proximal third of the medial trochlear ridge of the distal femur from six healthy foals that were 1, 24, 35, 47, 118 and 122â days old and of different breeds and sexes was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunohistochemistry. The majority of patent cartilage canals contained blood vessels that were lined by a thin layer of continuous endothelium. Fenestrations were found in two locations in one venule in a patent cartilage canal located deep in the growth cartilage and close to the ossification front in the 118-day-old foal. Chondrifying cartilage canals in all TEM-examined foals contained degenerated endothelial cells that were detached from the basement membrane, resulting in gap formation. Thirty-three percent of all canals were surrounded by a hypercellular rim that was interpreted as contribution of chondrocytes to growth cartilage. On LM, 69% of all cartilage canals were surrounded by a ring of matrix that stained intensely eosinophilic and consisted of collagen fibres on TEM that were confirmed to be collagen type I by immunohistochemistry. In summary, two types of discontinuity were observed in the endothelium of equine epiphyseal cartilage canal vessels: fenestrations were observed in a patent cartilage canal in the 118-day-old foal; and gaps were observed in chondrifying cartilage canals in all TEM-examined foals. Canals were not surrounded by any cellular wall, but a large proportion was surrounded by an acellular wall consisting of collagen type I. Bacterial binding can therefore probably occur in horses by mechanisms that are similar to those previously demonstrated in pigs and chickens.