RESUMEN
We report a very rare case of a dedifferentiated chondrosarcoma mimicking a benign giant cell tumor. A 22-year-old male was admitted to our hospital with a history of mild left wrist pain after a skiing trauma. Radiology revealed an extensive meta-epiphyseal osteolytic lesion in the distal ulna, which appeared to be a giant cell tumor. Histological examination showed a biphasic tumor comprising chondroid and non-chondroid areas with a giant cell-rich lesion resembling a conventional giant cell tumor of the bone. Immunohistochemistry showed no expression of p16(INK4a), VEGFR1, KDR (VEGFR2), VEGFR3, cKIT, MDM2 or CDK4. However, high expression of the tyrosine kinases PDGFRA and PDGFRB was observed. Molecular analysis showed no amplification of the cMYC gene and no activating mutations in the cKIT (exons 9 and 11) or PDGFRA (exon 18) genes. He has been on follow-up for ten months, with no evidence of local recurrence or metastatic disease. In summary, this report highlights a very rare case of a dedifferentiated chondrosarcoma in which the dedifferentiated component of the tumor bears histologic resemblance to a conventional giant cell tumor of bone. We suggest that this tumor might be categorized in the group of low-grade dedifferentiated chondrosarcomas.
Asunto(s)
Neoplasias Óseas/patología , Desdiferenciación Celular , Condrosarcoma/patología , Tumor Óseo de Células Gigantes/patología , Cúbito/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Óseas/enzimología , Neoplasias Óseas/genética , Neoplasias Óseas/cirugía , Condrosarcoma/enzimología , Condrosarcoma/genética , Condrosarcoma/cirugía , Análisis Mutacional de ADN , Diagnóstico Diferencial , Tumor Óseo de Células Gigantes/enzimología , Tumor Óseo de Células Gigantes/genética , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Imagen por Resonancia Magnética , Masculino , Clasificación del Tumor , Valor Predictivo de las Pruebas , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Cúbito/enzimología , Cúbito/cirugía , Adulto JovenRESUMEN
Matrix metalloproteinase-13 (MMP-13), is a key protein of bone matrix degradation, and is highly expressed by osteoblasts. We used the osteoblast-like MC3T3-E1 cell line and compared the stimulatory effects of the bone resorptive agents 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) 3,3',5-triido-L-thyronine (T3) on the expression of MMP-13 mRNA. We showed that the stimulatory effects were time and dose dependent, and were also transduced to the protein level, with 1,25-(OH)(2)D(3)being more potent.MMP-13 expression in different mouse cells and its localization within developing bone from the onset of osteogenesis were also investigated. 1,25-(OH)(2)D(3)- and T3-regulated osteocalcin (Osc) expression in mouse osteoblasts was compared to hormonal effects on MMP-13 expression and activity. Here we show divergent and common roles of 1,25-(OH)(2)D(3)and T3 action on the expression of these marker proteins, depending on the stage of cell differentiation. In addition, we propose a role for MMP-13 in the bone collar of developing long bones. The results could help to more precisely characterize hormonal regulation in the developmental sequence of osteoblasts.
Asunto(s)
Calcitriol/metabolismo , Diferenciación Celular/fisiología , Colagenasas/genética , Osteoblastos/enzimología , Osteocalcina/metabolismo , Triyodotironina/metabolismo , Animales , Animales Recién Nacidos , Matriz Ósea/efectos de los fármacos , Matriz Ósea/enzimología , Resorción Ósea/inducido químicamente , Resorción Ósea/enzimología , Calcitriol/farmacología , Diferenciación Celular/efectos de los fármacos , Colagenasas/biosíntesis , Relación Dosis-Respuesta a Droga , Feto , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/fisiología , Metaloproteinasa 13 de la Matriz , Ratones , Ratones Endogámicos C3H , Células 3T3 NIH , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Radio (Anatomía)/efectos de los fármacos , Radio (Anatomía)/enzimología , Radio (Anatomía)/crecimiento & desarrollo , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Cráneo/efectos de los fármacos , Cráneo/enzimología , Cráneo/crecimiento & desarrollo , Triyodotironina/farmacología , Cúbito/efectos de los fármacos , Cúbito/enzimología , Cúbito/crecimiento & desarrolloRESUMEN
We have previously shown that p38 mitogen-activated protein kinase (MAPK) inhibitors, which block the production and action of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), are effective in models of bone and cartilage degradation. To further investigate the role of p38 MAPK, we have studied its activation in osteoblasts and chondrocytes, following treatment with a panel of proinflammatory and osteotropic agents. In osteoblasts, significant activation of p38 MAPK was observed following treatment with IL-1 and TNF, but not parathyroid hormone, transforming growth factor-beta (TGF-beta), 1,25(OH)(2)D(3), insulin-like growth factor-1 (IGF-1), or IGF-II. Similar results were obtained using primary bovine chondrocytes and an SV40-immortalized human chondrocyte cell line, T/C28A4. SB 203580, a selective inhibitor of p38 MAPK, inhibited IL-1 and TNF-induced p38 MAPK activity and IL-6 production (IC(50)s 0.3--0.5 microM) in osteoblasts and chondrocytes. In addition, IL-1 and TNF also activated p38 MAPK in fetal rat long bones and p38 MAPK inhibitors inhibited IL-1- and TNF-stimulated bone resorption in vitro in a dose-dependent manner (IC(50)s 0.3--1 microM). These data support the contention that p38 MAPK plays a central role in regulating the production of, and responsiveness to, proinflammatory cytokines in bone and cartilage. Furthermore, the strong correlation between inhibition of kinase activity and IL-1 and TNF-stimulated biological responses indicates that selective inhibition of the p38 MAPK pathway may have therapeutic utility in joint diseases such as rheumatoid arthritis (RA).
Asunto(s)
Resorción Ósea/enzimología , Interleucina-1/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Bioensayo , Radioisótopos de Calcio/análisis , Radioisótopos de Calcio/metabolismo , Bovinos , Células Cultivadas , Condrocitos/citología , Condrocitos/efectos de los fármacos , Condrocitos/enzimología , Técnicas de Cultivo , Citocinas/farmacología , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Inhibidores Enzimáticos/farmacología , Sustancias de Crecimiento/farmacología , Humanos , Interleucina-1/farmacología , Interleucina-6/biosíntesis , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/enzimología , Radio (Anatomía)/citología , Radio (Anatomía)/embriología , Radio (Anatomía)/enzimología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Cúbito/citología , Cúbito/embriología , Cúbito/enzimología , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Heme oxygenases (HO) are responsible for the production of carbon monoxide, which has been suggested to act similarly to nitric oxide as a signaling molecule. Inducible HO-1 and constitutive HO-2 were located in sections of weight-bearing ulnae of the rat by immunocytochemistry. Intense HO-1 localization was restricted to peri- and endosteal sites, whereas HO-2 staining occurred in osteoblasts and osteocytes throughout the cortex. Northern blot hybridization of mRNA levels for HO-1 and HO-2 extracted from bones was also performed. Six hours after a single 10 min period of noninvasive mechanical loading of the ulna in vivo, generating physiological levels of strain sufficient to initiate an osteogenic response, the level of mRNA for the inducible HO-1 isoform was increased, but that of HO-2 was unchanged. The presence of a constitutive and strain-related upregulation of an inducible enzyme capable of producing carbon monoxide suggests that carbon monoxide may participate not only in bone cells' basal metabolism but also in their adaptive response to mechanical load.
Asunto(s)
Hemo Oxigenasa (Desciclizante)/biosíntesis , ARN Mensajero/biosíntesis , Cúbito/enzimología , Animales , Northern Blotting , Cartilla de ADN/química , Femenino , Hemo Oxigenasa (Desciclizante)/genética , Hemo-Oxigenasa 1 , Técnicas para Inmunoenzimas , Osteoblastos/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estrés Mecánico , Cúbito/citología , Soporte de Peso/fisiologíaRESUMEN
Responses to mechanical strain in calvaria and limb bone organ cultures were compared by measuring cellular glucose 6-phosphate dehydrogenase (G6PD) activity in situ and prostaglandin release. Normal functional strains were recorded in the ulnae (1000 mu epsilon) and calvarium (30 mu epsilon) in vivo in 110 g rats. Organ cultures of ulnae and calvaria from similar animals were loaded to produce dynamic strains (600 cycles, 1 Hz) of 1000 mu epsilon in the ulna, and 100 or 1000 mu epsilon in calvaria. In ulnae, both PGE2 and PGI2 were released and resident osteocytes and osteoblasts showed increased G6PD activity. Neither response was seen in calvaria. However, exogenous PGI2 (10(-5)-10(-9) M) stimulated G6PD activity in osteocytes and osteoblasts in organ cultures of both calvaria and ulnae. In ulnar cells the response was linear, in calvarial cells it was biphasic with maximum activity at 10(-7) M. Osteoblasts derived from ulnae and cultured on plastic plates subjected to dynamic strain (600 cycles, 1 Hz, 4000 mu epsilon) showed increased G6PD activity. There was no such response in similarly treated calvarial-derived cells. Calvarial bone cells differ from those of the ulna in that they do not respond to physiological strains in their locality with increased prostanoid release or G6PD activity either in situ or when seeded onto dynamically strained plastic plates. Cells from both sites in organ culture show increased G6PD activity in response to exogenous PGI2, but their dose:responses differ in shape. These differences may reflect the extent to which functional loading influences bone architecture in these two sites.
Asunto(s)
Epoprostenol/farmacología , Glucosafosfato Deshidrogenasa/metabolismo , Cráneo/enzimología , Cúbito/enzimología , Animales , Células Cultivadas , Estimulación Eléctrica , Glucosafosfato Deshidrogenasa/efectos de los fármacos , Miembro Posterior , Técnicas de Cultivo de Órganos , Osteoblastos/efectos de los fármacos , Osteoblastos/enzimología , Osteocitos/efectos de los fármacos , Osteocitos/enzimología , Hueso Parietal/citología , Hueso Parietal/efectos de los fármacos , Hueso Parietal/fisiología , Ratas , Cráneo/fisiología , Estrés Mecánico , Resistencia a la Tracción/fisiología , Cúbito/fisiologíaRESUMEN
Activities of alkaline and acid phosphatases in ulnar and radial bones of rats flown for 18.5 days aboard Cosmos-936 and kept in a ground-based mock-up were investigated. In both bones activity of acid phosphatase increased significantly and that of alkaline phosphatase decreased 6--10 hours postflight; in the synchronous experiment the only change was a decrease in the activity of alkaline phosphatase in the radius. An exposure of rats to artificial gravity did not normalize changes in phosphatase activities observed postflight. At R + 25 phosphatase activity in bones of flight rats returned to normal and even tended to exceed the control level in synchronous animals.
Asunto(s)
Fosfatasa Ácida/metabolismo , Fosfatasa Alcalina/metabolismo , Radio (Anatomía)/enzimología , Vuelo Espacial , Cúbito/enzimología , Animales , Masculino , RatasRESUMEN
Photon absorption measurements of forearm bone density in 196 insulin-dependent patients, age 6--26 years, were compared with findings in 124 controls. Expected density, gm. Ca/cm.2 bone width (M/W), was calculated from regressions of M/W on ulnar length for white and black male and female controls. There were no significant correlations between M/W differences from expected and serum Ca, Mg, P, or alkaline phosphatase levels, estimated physical activity level, insulin dosage, or the presence of joint contracture. White females averaged 8.2 per cent (+/- 1 S.E.M.) loss of M/W, as against white male average loss of 4.7 per cent +/- 1 and black female loss of 2 per cent +/- 2 (p less than 0.001); the black male population was too small for separate analysis. M/W loss greater than 10 per cent was seen in 29 per cent of white males, 19 per cent of blacks, and 48 per cent of white females (p less than 0.02). When the groups were further divided into those with duration of diabetes less than or equal to five years and those with duration greater than five years, significant reduction in M/W average loss over time was seen with white females (10.6 per cent +/- 1.2 to 3.7 per cent+/- 1.5, p less than 0.0001). Expression of this defect in bone mineralization is controlled by race and sex acting independently of each other.