Dataset Information

Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

ABSTRACT: Type 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralateral tibia in T2D mice. Male C57BL/6 mice were fed either a low-fat diet (LFD) or high-fat diet (HFD) starting at 8 weeks. After 12 weeks, the T2D phenotype in HFD mice was confirmed via glucose and insulin tolerance testing and echoMRI, and all mice underwent SBD surgery. Mice were treated with BMP-2 (5 µg) or saline at the time of surgery. Three weeks postsurgery, bone marrow ECs were isolated from ipsilateral and contralateral tibias, and proliferation, angiogenic potential, and gene expression of the cells was analyzed. BMP-2 treatment increased EC proliferation by two fold compared with saline in LFD contralateral tibia ECs, but no changes were seen in surgical tibia EC proliferation. BMP-2 treatment enhanced vessel-like structure formation in HFD mice whereas, the opposite was observed in LFD mice. Still, in BMP-2 treated LFD mice, ipsilateral tibia ECs increased expression of CD31, FLT-1, ANGPT1, and ANGPT2. These data suggest that the modulating effects of T2D and BMP-2 on the microenvironment of bone marrow ECs may differentially influence angiogenic properties at the fractured limb versus the contralateral limb.

SUBMITTER: Dadwal UC

PROVIDER: S-EPMC8435543 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Dadwal Ushashi C UC Staut Caio de Andrade CA Tewari Nikhil P NP Awosanya Olatundun D OD Mendenhall Stephen K SK Valuch Conner R CR Nagaraj Rohit U RU Blosser Rachel J RJ Li Jiliang J Kacena Melissa A MA

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20210326 2

Type 2 diabetes (T2D) results in physiological and structural changes in bone, contributing to poor fracture healing. T2D compromises microvascular performance, which can negatively impact bone regeneration as angiogenesis is required for new bone formation. We examined the effects of bone morphogenetic protein-2 (BMP-2) administered locally at the time of femoral segmental bone defect (SBD) surgery, and its angiogenic impacts on endothelial cells (ECs) isolated from the ipsilateral or contralat ...[more]

PMID: 33713476

Similar Datasets

Project description:BackgroundAccurate prediction is essential for the effective management of spontaneous pneumothorax (SP). To improve prediction, this study primarily focuses on using simple chest X-rays to predict ipsilateral recurrence and contralateral occurrence of SP.MethodsAll consecutive subjects diagnosed with SP from July 2017 to June 2023 were retrospectively reviewed. Ipsilateral recurrence and contralateral occurrence of SP within two years of completing treatment were analyzed. Using simple chest X-rays and clinical parameters such as age, sex, smoking, chronic obstructive pulmonary disease (COPD) and surgery, machine learning algorithms were applied to predict SP development. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to highlight the X-ray regions associated with SP development.ResultsThe study included 1,086 cases of SP, with 546 right-side and 540 left-side developments. Surgeries were performed in 243 right and 204 left cases. Ipsilateral recurrence occurred in 93 cases total, while contralateral occurrence occurred in 60 right and 34 left cases. For predicting ipsilateral recurrence in the young group, gradient boosting (GB) [area under curve (AUC) of 0.686, accuracy of 0.769, F1 score of 0.733, precision of 0.706, and recall of 0.769] for the right side and logistic regression (AUC of 0.628, accuracy of 0.781, F1 score of 0.753, precision of 0.737, and recall of 0.781) for the left side were the top-performing models. In the older group, K-nearest neighbors (KNN) (AUC of 0.615, accuracy of 0.801, F1 score of 0.760, precision of 0.735, and recall of 0.801) for the right side and logistic regression (AUC of 0.623, accuracy of 0.824, F1 score of 0.804, precision of 0.794, and recall of 0.824) for the left side were the best models. For predicting contralateral occurrence in the young group, random forest (RF) (AUC of 0.597, accuracy of 0.774, F1 score of 0.741, precision of 0.709, and recall of 0.774) for the right side and KNN (AUC of 0.650, accuracy of 0.893, F1 score of 0.849, precision of 0.809, and recall of 0.893) for the left side were the most effective models. In the older group, logistic regression (AUC of 0.630, accuracy of 0.935, F1 score of 0.914, precision of 0.894, and recall of 0.935) for the right side and neural network (NN) (AUC of 0.765, accuracy of 0.961, F1 score of 0.948, precision of 0.936, and recall of 0.961) for the left side were the top performers. Grad-CAM analysis revealed that apical lung portions were strongly associated with both ipsilateral recurrence and contralateral occurrence of SP.ConclusionsThe results of this study suggest that machine learning algorithms using simple X-rays and basic clinical data can predict SP development with fair performance. The apical regions of the lung were strongly associated with SP development, consistent with clinical knowledge.

Project description:BackgroundThe neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. We investigated whether commissural projections in prefrontal cortices are organized according to the same or different rules as those within the same hemisphere, by quantitatively comparing density, topography, and laminar origin of contralateral and ipsilateral projections, labeled after unilateral injection of retrograde tracers in prefrontal areas.ResultsCommissural projection neurons constituted less than one third of the ipsilateral. Nevertheless, projections from the two hemispheres were strongly correlated in topography and relative density. We investigated to what extent the distribution of contralateral projections depended on: (a) geographic proximity of projection areas to the area homotopic to the injection site; (b) the structural type of the linked areas, based on the number and neuronal density of their layers. Although both measures were good predictors, structural type was a comparatively stronger determinant of the relative distribution and density of projections. Ipsilateral projection neurons were distributed in the superficial (II-III) and deep (V-VI) layers, in proportions that varied across areas. In contrast, contralateral projection neurons were found mostly in the superficial layers, but still showed a gradient in their distribution within cortical layers that correlated significantly with cortical type, but not with geographic proximity to the homotopic area.ConclusionThe organization of ipsilateral and contralateral prefrontal projections is similar in topography and relative density, differing only by higher overall density and more widespread laminar origin of ipsilateral than contralateral projections. The projections on both sides are highly correlated with the structural architecture of the linked areas, and their remarkable organization is likely established by punctuated development of distinct cortical types. The preponderance of contralateral projections from layer III may be traced to the late development of the callosal system, whose function may be compromised in diseases that have their root late in ontogeny.

Dataset Information

Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Publications

Effects of diet, BMP-2 treatment, and femoral skeletal injury on endothelial cells derived from the ipsilateral and contralateral limbs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets