RESUMEN
OBJECTIVE: To determine if early supplemental intra-articular α2-macroglobulin (A2M) has a chondroprotective effect in a collagen II-induced arthritis (CIA) mice model. METHODS: DBA/1 mice were randomized into four groups (n = 15/group): (a) CIA + 1.2 µg of A2M; (b) CIA + 0.8 µg of A2M; (c) CIA + 0.4 µg of A2M; (d) vehicle + phosphate-buffered saline (PBS). A2M was injected into right ankles and PBS was injected into the left ankles simultaneously as internal control at days 36, 43 and 50. The CIA inflammation clinical score and ankle thickness were recorded every other day starting on day 21 until sacrifice. Changes in inflammation were monitored by in vivo fluorescence molecular tomography (FMT). Inflammation, cartilage and bone damage were assessed with X-ray, histology and immunohistochemistry. Cartilage and inflammation-related gene expression was quantified by real-time polymerase chain reaction (PCR). RESULTS: All mice showed ankle inflammation on day 33. After day 43, lower clinical scores, ankle thickness and Sharp/van der Heijde method scores in A2M-treated ankles compared with PBS-treated ankles. FMT data indicated that the inflammation markers MMPSense and ProSense were significantly elevated in the PBS-treated ankles than A2M-treated ankles. Histology and X-ray analyses indicated that A2M administration resulted in lower levels of inflammatory infiltration and synovial hyperplasia, as well as more typical cartilage and bone organization with increased COL II and Aggrecan staining when compared with PBS-treated ankles. In addition, real-time PCR showed that,matrix metalloproteinase-3, -9, -13, COL X and Runx2 were significantly less expressed in A2M-treated groups than PBS-treated animals. CONCLUSION: Early supplemental intra-articular A2M exerts an anti-inflammatory effect and attenuates cartilage and bone damage in a CIA model.
Asunto(s)
Antiinflamatorios/administración & dosificación , Artritis Experimental/prevención & control , Cartílago Articular/efectos de los fármacos , Colágeno Tipo II , Huesos del Pie/efectos de los fármacos , Articulaciones del Pie/efectos de los fármacos , alfa 2-Macroglobulinas Asociadas al Embarazo/administración & dosificación , Agrecanos/genética , Agrecanos/metabolismo , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/inmunología , Artritis Experimental/patología , Remodelación Ósea/efectos de los fármacos , Cartílago Articular/inmunología , Cartílago Articular/metabolismo , Cartílago Articular/patología , Condrogénesis/efectos de los fármacos , Citocinas/genética , Citocinas/metabolismo , Femenino , Huesos del Pie/inmunología , Huesos del Pie/metabolismo , Huesos del Pie/patología , Articulaciones del Pie/inmunología , Articulaciones del Pie/metabolismo , Articulaciones del Pie/patología , Regulación de la Expresión Génica/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Inyecciones Intraarticulares , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Ratones Endogámicos DBA , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the relationships between changes in serum urate levels and dual-energy computed tomography (DE-CT) results during urate-lowering therapy (ULT) and to investigate the effects of treatment duration and drugs on changes in DE-CT results. METHODS: Forty-four patients diagnosed with gout were enrolled in this investigation. DE-CT was conducted on the foot at baseline and the end of follow-up (6-24 months). Crystals were classified as: (i) L, number of large crystals with diameter ≥ 3 mm; (ii) S, number of small crystals with diameter < 3 mm; (iii) T, total number of crystals; and (iv) Vmax, volume of the maximal crystal. RESULTS: Number of urate crystals (L, S as well as T) and Vmax decreased significantly through ULT. Significant decrease of urate crystal numbers and/or Vmax was observed in different follow-up groups, and the decrease in serum urate levels was positively related to the decrease of T (r = 0.43, P = 0.04) and Vmax (r = 0.63, P = 0.04). Moreover, analysis of covariance results demonstrated significant effects of treatment duration and serum urate levels on results of DE-CT. CONCLUSION: Both urate crystal numbers and Vmax decreased significantly during ULT. Additionally, ULT duration and serum urate levels had significant effects on the decrease of Vmax and number of large crystals measured by DE-CT.
Asunto(s)
Artritis Gotosa/diagnóstico por imagen , Artritis Gotosa/tratamiento farmacológico , Monitoreo de Drogas/métodos , Huesos del Pie/efectos de los fármacos , Huesos del Pie/diagnóstico por imagen , Supresores de la Gota/uso terapéutico , Tomografía Computarizada por Rayos X , Ácido Úrico/sangre , Adulto , Anciano , Artritis Gotosa/sangre , Biomarcadores/sangre , Cristalización , Femenino , Huesos del Pie/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
Leg and foot bones of adult and juvenile red grouse (Lagopus lagopus scoticus) were collected from hunter-shot birds on two Scottish estates (Glendye and Invermark) and one Yorkshire estate in September, 2003. The lead content of bones was measured by atomic absorption spectrophotometry, and corresponding stable lead isotopes (Pb(204, 206, 207, 208)) by inductively coupled plasma mass spectrometry. At the Glendye (N=111) and Invermark (N=85) estates, relatively few birds (5.4% and 3.5%, respectively) had highly elevated bone lead concentrations (>20 microg/g dry weight). In bones of these highly exposed birds, a combination of Pb(206):Pb(207) and Pb(208):Pb(207)ratios was consistent with ingestion of lead gunshot available in Europe. By contrast, Yorkshire grouse experienced a high incidence (65.8%) of bone lead >20 microg/g. The Pb(206):Pb(207) and Pb(208):Pb(207)ratios in bones of these highly exposed birds were consistent with a combined exposure to ingested lead gunshot and lead from galena mining in the region. Lead isotope ratios also indicated that lead from UK gasoline combustion and fallout from atmospheric particles was not a likely source of elevated lead in bones of either Scottish or Yorkshire grouse. Suggested management options for the three moors include adopting nontoxic shot for all game shooting on the estates, allowing heather (Calluna vulgaris) vegetation to grow tall in lead shot fall-out zones to reduce physical access to high densities of lead shot already present, and provision of calcareous grit across moors to reduce lead assimilation from all ingested sources of lead.
Asunto(s)
Contaminantes Ambientales/metabolismo , Huesos del Pie/metabolismo , Galliformes , Plomo/metabolismo , Huesos de la Pierna/metabolismo , Animales , Inglaterra , Contaminantes Ambientales/química , Isótopos , Plomo/química , Escocia , Espectrofotometría AtómicaRESUMEN
UNLABELLED: The pathogenesis of Charcot neuroarthropathy is unclear. To investigate the possibility that decreased levels of calcitonin gene-related peptide and endothelial nitric oxide synthase are involved in the process, we studied bone samples from healthy subjects (n = 4), subjects with diabetic neuropathy (n = 4), and subjects with Charcot neuroarthropathy (n = 4). A statistically significant difference was found in endothelial nitric oxide synthase expression between bone specimens in patients with diabetic neuropathy, Charcot neuroarthropathy, and normal bone (P = .008). A trend toward calcitonin gene-related peptide intensification was observed in normal bone as compared to diabetic neuropathy and Charcot neuroarthropathy bone specimens, but it did not reached statistical significance (P = .23). This pilot study suggests that abnormal calcitonin gene-related peptide and endothelial nitric oxide synthase activity may play a role in the development of Charcot neuroarthropathy. LEVEL OF CLINICAL EVIDENCE: 4.
Asunto(s)
Artropatía Neurógena/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Huesos del Pie/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Artropatía Neurógena/cirugía , Pie Diabético/metabolismo , Femenino , Huesos del Pie/cirugía , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Morphological characteristics of bone tissues were studied in the feet of patients with diabetes mellitus type 1 and 2 (DM1 and DM2). Osteoblasts and osteoclasts prevalence, the presence of collagen type III in the composition of newly formed bone were characteristic for DM1. Osteocytes prevalence and abundant granulation tissue in newly formed bone was a feature of DM2. The analysis of bone tissue resorption suggests that lacunar osteoclastic resorpsion is the main type in DM1 while periosteocytic osteolysis and smooth resorption are typical for DM2. Thus, osteolysis genesis and synthesis of bone tissue in DM1 and DM2 may be different.
Asunto(s)
Resorción Ósea/patología , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/patología , Pie Diabético/patología , Huesos del Pie/patología , Adulto , Anciano , Resorción Ósea/etiología , Resorción Ósea/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Pie Diabético/complicaciones , Pie Diabético/metabolismo , Femenino , Fibronectinas/metabolismo , Huesos del Pie/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Osteólisis/etiología , Osteólisis/metabolismo , Osteólisis/patología , SíndromeRESUMEN
Cartilage oligomeric matrix protein has been implicated as an important component of endochondral ossification because of its direct effects on chondrocytes. The importance of this protein for skeletal development and growth has been recently illustrated by the identification of mutations in cartilage oligomeric protein genes in two types of inherited chondrodysplasias and osteoarthritic phenotypes: multiple epiphyseal dysplasia and pseudoachondroplasia. In the present study, we report the presence of cartilage oligomeric protein in embryonic and adult osteoblasts. A foot from a 21-week-old human fetus, subchondral bone obtained from knee replacement surgery in an adult patient, and a limb from a 19-day-postcoital mouse embryo were analyzed with immunostaining and in situ hybridization. In the human fetal foot, cartilage oligomeric protein was localized to osteoblasts of the bone collar and at the newly formed bone at the growth plate and bone diaphyses. Immunostaining was performed on the adult subchondral bone and showed positive intracellular staining for cartilage oligomeric protein of the osteoblasts lining the trabecular bone. There was no staining of the osteocytes. Immunostaining of the mouse limb showed the most intense staining for cartilage oligomeric protein in the hypertrophic chondrocytes and in the surrounding osteoblast cells of the developing bone. Cartilage oligomeric protein mRNA and protein were detected in an osteoblast cell line (MG-63), and cartilage oligomeric protein mRNA was detected from human cancellous bone RNA. These results suggest that the altered structure of cartilage oligomeric protein by the mutations seen in pseudoachondroplasia and multiple epiphyseal dysplasia may have direct effects on osteoblasts, contributing to the pathogenesis of these genetic disorders.