scholarly journals The mouse bone metabolome is sexually dimorphic and is associated with whole bone strength

2021 ◽  
Author(s):  
Hope D Welhaven ◽  
Ghazal Vahidi ◽  
Seth T Walk ◽  
Brian Bothner ◽  
Chelsea M Heveran ◽  
...  

The material properties of bone tissue depend on the activity of remodeling bone cells, but the impact of bone cell metabolism on bone tissue is uncertain. To date, the metabolome of bone has not been evaluated for cortical bone, bone marrow, or whole bone including both tissue types. Furthermore, it is of particular interest whether the cortical bone metabolome reflects the sexual dimorphism observed in cortical bone material properties. We hypothesized that the metabolome of cortical bone differs from that of bone marrow, and that the cortical bone metabolome is sexually dimorphic. We first evaluated the metabolic profiles of isolated cortical bone, bone marrow, and whole bone for 20-week female C57Bl/6 mice (n = 10). We then compared metabolic profiles for isolated cortical bone from a separate group of 20-week female and male C57Bl6/mice (n = 10 / sex). Femurs from the same mice were evaluated for flexural material properties. Strength groupings (high strength males, high strength females, low strength males) were utilized to inform comparisons in the isolated humerus cortical bone metabolome. The metabolome of isolated cortical bone, bone marrow, and whole bone are distinct. The isolated cortical bone metabolome is also distinct between males and females. The female mice show evidence of lipid metabolism, whereas male mice show evidence of amino acid metabolism. Finally, 12 metabolic pathways were differentially regulated between bones that differed in strength. High-strength bones from both male and female mice included metabolites associated with tryptophan and purine metabolism. Taken together, these data demonstrate the power of metabolomics to provide insight into the effects of metabolism on bone physiology. These data add to an intricate picture of bone as an organ that is sexually dimorphic both in material and metabolomic profiles.

2020 ◽  
Vol 5 (48) ◽  
pp. eabc4466 ◽  
Author(s):  
C. C. Bain ◽  
D. A. Gibson ◽  
N. J. Steers ◽  
K. Boufea ◽  
P. A. Louwe ◽  
...  

Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis, and metastatic cancer; thus, understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover, and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single-cell RNA sequencing revealed marked dimorphisms in gene expression between male and female peritoneal macrophages that was, in part, explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2−/− mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow, whereas others are reliant on local microenvironment signals. We demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious diseases.


2018 ◽  
Vol 57 ◽  
pp. 56-66 ◽  
Author(s):  
Guanjun Zhang ◽  
Xianpan Deng ◽  
Fengjiao Guan ◽  
Zhonghao Bai ◽  
Libo Cao ◽  
...  

2019 ◽  
Author(s):  
Calum C. Bain ◽  
Douglas A. Gibson ◽  
Nicholas Steers ◽  
Katarina Boufea ◽  
Pieter A. Louwe ◽  
...  

AbstractMacrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the aetiology of pathologies including peritonitis, endometriosis and metastatic cancer thus understanding the factors that govern their behaviour is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single cell RNAseq revealed striking dimorphisms in gene expression between male and female peritoneal macrophages that was in part explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2−/− mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow while others are reliant on local microenvironment signals. Importantly, we demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious disease.


Author(s):  
SS Miranda ◽  
DJ Cruz ◽  
RL Amaral ◽  
AD Santos ◽  
J César de Sá ◽  
...  

The plastic deformation included in the technological processes of sheet metal forming allows the production of different components with different geometries. Therefore, the formability of metallic materials is an essential feature in stamping processes. One of the inevitable scattering sources when considering these processes is the variability of material properties, which can change from coil to coil, from batch to batch and from supplier to supplier. This constitutes a significant obstacle in improving the quality of any manufacturing process. The current study investigates the formability and the mechanical characterization of a defined advanced high strength steel grade, considering different suppliers, coils, and batches in order to evaluate its influence on the results of the sheet metal forming process. A microstructure analysis is also considered to understand the impact of micro-scale variables (e.g. grain size) in macro-scale behavior. Additionally, numerical simulations were taken into consideration to evaluate the influence of mechanical characterization in the results.


2009 ◽  
Vol 27 (10) ◽  
pp. 1272-1279 ◽  
Author(s):  
Rachel C. Entwistle ◽  
Sara C. Sammons ◽  
Robert F. Bigley ◽  
Scott J. Hazelwood ◽  
David P. Fyhrie ◽  
...  

2006 ◽  
Vol 2 (2) ◽  
pp. 114-123 ◽  
Author(s):  
N. Peixinho ◽  
A. Pinho

This study reports on modeling the mechanical behavior of high-strength steels subjected to impact loading. The materials studied were steel grades of interest for crashworthiness applications: dual-phase and transformation induced plasticity (TRIP) steels. The challenges associated with the numerical simulation of impact events involving these materials include the modeling of extensive plastic deformation, particularly the change of material properties with strain rate. Tensile testing was performed at different strain rates on the materials studied. The test results were used to compare and validate constitutive equations that provide a mathematical description of strain-rate dependence of the material properties. The Cowper–Symonds equation and modified variants were examined. The crashworthiness performance of thin-walled sections made of dual-phase and TRIP steels was also investigated. Axial crushing tests were performed at different speeds on top-hat and hexagonal tubes. The experimental results were compared with numerical simulations obtained using an explicit finite element program (LS-DYNA) and the original and modified Cowper–Symonds equations.


2019 ◽  
Vol 47 (4) ◽  
pp. 937-952 ◽  
Author(s):  
Guanjun Zhang ◽  
Shujing Wang ◽  
Songyang Xu ◽  
Fengjiao Guan ◽  
Zhonghao Bai ◽  
...  

2008 ◽  
Vol 1 (4) ◽  
pp. A353
Author(s):  
Shenandoah Robinson ◽  
Qing Li

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.


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