Project description:Obesity has emerged as a worldwide problem in human health. Dietary lipids are taken up and transported via lymphatics into the circulatory system. During this process, lipids pass the mesenteric lymph node (mLN). These organs filter the lymph fluid for foreign antigens to induce and control immune responses. Alteration of that function during obesity has only slightly been studied. Here, we characterize changes within the microarchitecture of the mLN during high levels of lipid transport and highlight the role of stromal cells. Microarray experiments detected gene probes expressed by mLN stromal cells. Transmission electron microscopy enabled us to identify lipid droplets in different stromal cells, and in macrophages. Sizes, numbers and intercellular distances increased after 10 weeks of a high-fat diet. Thus, we propose that changes in the microarchitecture and increased accumulation of lipid droplets in stromal cells and macrophages have an influence on the immunological function of the mLN.
Project description:Obesity has emerged as a worldwide problem in human health. Dietary lipids are taken up and transported via lymphatics into the circulatory system. During this process, lipids pass the mesenteric lymph node (mLN). These organs filter the lymph fluid for foreign antigens to induce and control immune responses. Alteration of that function during obesity has only slightly been studied. Here, we characterize changes within the microarchitecture of the mLN during high levels of lipid transport and highlight the role of stromal cells. Microarray experiments detected gene probes expressed by mLN stromal cells. Transmission electron microscopy enabled us to identify lipid droplets in different stromal cells, and in macrophages. Sizes, numbers and intercellular distances increased after 10 weeks of a high-fat diet. Thus, we propose that changes in the microarchitecture and increased accumulation of lipid droplets in stromal cells and macrophages have an influence on the immunological function of the mLN.
Project description:Collagen XI alpha 1 (Col11a1) is an extracellular matrix molecule required for embryonic development with a role in both nucleating the formation of fibrils and regulating the diameter of heterotypic fibrils during collagen fibrillar assembly. Although found in many different tissues throughout the vertebrate body, Col11a1 plays an essential role in endochondral ossification. To further understand the function of Col11a1 in the process of bone formation, we compared skeletal mineralization in wild-type (WT) mice and Col11a1-deficient mice using X-ray microtomography (micro-CT) and histology. Changes in trabecular bone microstructure were observed and are presented here. Additionally, changes to the periosteal bone collar of developing long bones were observed and resulted in an increase in thickness in the case of Col11a1-deficient mice compared to WT littermates. Vertebral bodies were incompletely formed in the absence of Col11a1. The data demonstrate that Col11a1 depletion results in alteration to newly-formed bone and is consistent with a role for Col11a1 in mineralization. These findings indicate that expression of Col11a1 in the growth plate and perichondrium is essential for trabecular bone and bone collar formation during endochondral ossification. The observed changes to mineralized tissues further define the function of Col11a1.
Project description:Tuberculosis is among the leading causes of death from infectious diseases and affects many organ systems, including the skeleton. Skeletal tuberculosis is an extrapulmonary stage of tuberculosis, which occurs after the early and post-primary pulmonary stages of the disease. The aim of our study was to assess the microarchitecture of historic dry bone samples of subjects who have died of tuberculosis documented by post-mortem examinations. These preparations date to the pre-antibiotic era, and were provided by the Pathological-Anatomical Collection in the "Fools Tower" of the Natural History Museum Vienna (PASiN-NHM).We investigated macerated samples of 20 vertebral bodies, 19 femoral heads, and 20 tibiae of a total of 59 individuals diagnosed with tuberculosis from the nineteenth and early twentieth century. 10 femora and 10 tibiae from body donors that did not exhibit signs of infection and 10 (unaffected) vertebrae kept at the PASiN-NHM were studied as controls. The affected regions of the bone samples (and the corresponding regions of the control bones) were analyzed by microcomputed tomography using a Viscom X 8060 II system. Obtained images were analyzed semi-quantitatively. In samples with tuberculosis, independent of the investigated skeletal region, trabecular defects and decreased trabecular thickness were observed. Cortical porosity was seen in affected vertebrae and tibia; in tuberculous tibiae (but not in the femora) cortical thickness was decreased. In half of the individuals, cortical sclerosis was present; signs of ankylosis were observed mainly at the femoral heads affected with tuberculosis. We conclude that a combination of several alterations at the trabecular compartment could be suggestive of the presence of tuberculosis in historic skeletal remains.
Project description:The mechanism behind osteonecrosis of the femoral head (ONFH) remains unclear. The aim of this study was to explore the pathogenesis of ONFH from a biomechanical standpoint to provide a theoretical basis for improved treatments. We compared the bone structure of fractured femoral heads with that of necrotic femoral heads by Micro-CT scanning and histological evaluation. In addition, we compared the biomechanical properties of each zone in fractured femoral heads with those in necrotic femoral heads by using biomechanical tests. Compared with fractured femoral heads, bone microarchitecture and bone morphometry in necrotic zone and sclerotic zone of necrotic femoral heads have altered markedly. In addition, the biomechanical properties of the necrotic zone in femoral heads weaken markedly, while those of the sclerotic zone strengthen. We hypothesize that discordance between bone structure and function of the femoral head may be involved in the pathogenesis of ONFH and that more attention should be paid to the prevention and treatment of such discordance.
Project description:BackgroundTo gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.MethodsIn this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.ResultsThirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed.ConclusionsHigh-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.Level of evidenceTherapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.