The Lectin ArtinM Induces Recruitment of Rat Mast Cells from the Bone Marrow to the Peritoneal Cavity

Background: The D-mannose binding lectin ArtinM is known to recruit neutrophils, to degranulate mast cells and may have potential therapeutic applications. However, the effect of ArtinM on mast cell recruitment has not been investigated. Methodology: Male Wistar rats were injected i.p. with ArtinM or ConA (control). The ability of the lectin to degranulate peritoneal and mesenteric mast cells was examined. Recruitment of mast cells to the peritoneal cavity and mesentery after ArtinM injection was examined with or without depletion of peritoneal mast cells by distilled water. Results: ArtinM degranulated both peritoneal and mesentery mast cells in vitro. Three days after i.p. injection of the lectin there were reduced numbers of mast cells in the peritoneal lavage, while at 7 days post injection of ArtinM, the number of peritoneal mast cells was close to control values. Since immature mast cells are recruited from the bone marrow, the effect of the lectin on bone marrow mast cells was examined. Injection of ArtinM resulted in an increased number of mast cells in the bone marrow. To determine if degranulation of mast cells in the peritoneal cavity was required for the increase in bone marrow mast cells, the peritoneal cavity was depleted of mast cells with ultrapure water. Exposure to ArtinM increased the number of mast cells in the bone marrow of rats depleted of peritoneal mast cells. Conclusions: The ArtinM induced recruitment of mast cells from the bone marrow to the peritoneal cavity may partiall

Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors

<p>Abstract</p> <p>Background</p> <p>Mast cells have recently gained new importance as immunoregulatory cells that are involved in numerous pathological processes. One result of these processes is an increase in mast cell numbers at peripheral sites. This study was undertaken to determine the mast cell response in the peritoneal cavity and bone marrow during repopulation of the peritoneal cavity in rats.</p> <p>Results</p> <p>Two mast cell specific antibodies, mAb AA4 and mAb BGD6, were used to distinguish the committed mast cell precursor from more mature mast cells. The peritoneal cavity was depleted of mast cells using distilled water. Twelve hours after distilled water injection, very immature mast cells could be isolated from the blood and by 48 hours were present in the peritoneal cavity. At this same time the percentage of mast cells in mitosis increased fourfold. Mast cell depletion of the peritoneal cavity also reduced the total number of mast cells in the bone marrow, but increased the number of mast cell committed precursors.</p> <p>Conclusions</p> <p>In response to mast cell depletion of the peritoneal cavity, a mast cell progenitor is released into the circulation and participates in repopulation of the peritoneal cavity, while the committed mast cell precursor is retained in the bone marrow.</p

FAK-mediated mechanotransduction in skeletal regeneration

The majority of cells are equipped to detect and decipher physical stimuli, and then react to these stimuli in a cell type-specific manner. Ultimately, these cellular behaviors are synchronized to produce a tissue response, but how this is achieved remains enigmatic. Here, we investigated the genetic basis for mechanotransduction using the bone marrow as a model system. We found that physical stimuli produced a pattern of principal strain that precisely corresponded to the site-specific expression of sox9 and runx2, two transcription factors required for the commitment of stem cells to a skeletogenic lineage, and the arrangement and orientation of newly deposited type I collagen fibrils. To gain insights into the genetic basis for skeletal mechanotransduction we conditionally inactivated focal adhesion kinase (FAK), an intracellular component of the integrin signaling pathway. By doing so we abolished the mechanically induced osteogenic response and thus identified a critical genetic component of the molecular machinery required for mechanotransduction. Our data provide a new framework in which to consider how physical forces and molecular signals are synchronized during the program of skeletal regeneration

B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production.

A small subset of B cells, termed B-1 cells, with developmental origins, phenotypes, and functions that are distinct from those of conventional B cells exist in mice. It contributes the vast majority of spontaneously produced "natural" IgM. Natural IgM is constitutively produced, even in the absence of microbiota, and fulfills many distinct functions in tissue homeostasis and host defense. B-1 cells also respond with IgM production to innate signals and pathogen exposure, while maintaining steady-state levels natural IgM. Thus, within the B-1 cell pool, cells of distinct and heterogeneous functionality must exist to facilitate these different functions. This review considers three factors that may contribute to this heterogeneity: first, developmental differences regarding the origins of the precursors, second, tissue-specific signals that may differentially affect B-1 cells in the tissue compartments, and finally responsiveness to self-antigens as well as innate and antigen-specific signals. All three are likely to shape the repertoire and responsiveness of B-1 cells to homeostatic- and antigen-induced signals and thus contribute to the functional heterogeneity among these innate-like B cells

Both ion channels and calcium signals regulate proliferation in human adult mesenchymal stem cells from bone marrow

BACKGROUND: It has been recognized that human bone marrow-derived mesenchymal stem cells (MSCs) are present within the bone marrow cavity and serve as a reservoir for the ...postprintThe 9th Annual Meeting of the International Society for Stem Cell Research (ISSCR 2011), Toronto, Canada, 15-18 June 2011. In Thursday Poster Abstracts of ISSCR, 2011, p. 156, poster board no. 301

Exercise mediated regulation of medullary and extramedullary hematopoiesis

Bone marrow is the major site of adult hematopoiesis. Bone marrow cells exert control over the hematopoietic stem cells that reside in the niche; osteoblasts act as positive regulators while adipocytes act as negative regulators. Levels of circulating hematopoietic cytokines also regulate hematopoiesis. In this study, we demonstrate that an endurance exercise training program results in several changes that act to induce hematopoiesis. Bone marrow-derived mesenchymal stem cell differentiation is skewed away from adipogenesis and towards osteogenesis in exercise trained animals. As a result, the bone marrow cavity is remodeled during the training period and acts to facilitate hematopoiesis. Hematopoietic cytokine gene expression levels also increase in exercise trained skeletal muscle. These changes translate into increased bone marrow and blood hematopoietic stem and progenitor cell content. This study draws a link between exercise training, bone marrow niche regulation, skeletal muscle derived hematopoietic cytokines, and the regulation of hematopoiesis.Master of Science (MS

3d Solid Modeling and Pre-Static Finite Element Modeling of Intact Human Tibia

This paper presents a standard solid model for human tibia, accounting for the material characteristics of cortical bone, cancellous bone and bone marrow. A CT scan of a cadaveric human tibia was used as the basis of developed model. A total of 201 CT scan slices of the tibia were taken with the distances between the scans varying along the length of the bone with a higher density at the proximal and distal ends, as those were the regions of interest. The data was imported into MIMICS (Materialise), and the threshold method was used to differentiate between the cortical bone region, cancellous bone region, and the bone marrow cavity. The solid model used to generate the FE model is constructed based on CT scan data of an actual cadaveric human tibia. The geometric information is retrieved and edited in (MIMICS). The surfaces defining the cortical bone, the proximal and distal epiphyseal cancellous bone and medullar cavity regions are converted into NURBS surfaces using (GEOMAGIC STUDIO)

T2-based temperature monitoring in bone marrow for MR-guided focused ultrasound.

BackgroundCurrent clinical protocols for MR-guided focused ultrasound (MRgFUS) treatment of osseous lesions, including painful bone metastases and osteoid osteomas, rely on measurement of the temperature change in adjacent muscle to estimate the temperature of the bone. The goal of this study was to determine if T2-based thermometry could be used to monitor the temperature change in bone marrow during focused ultrasound ablation of bone lesions.MethodsWe investigated the dependence of T2 on temperature in ex vivo bovine yellow bone marrow at 3T and studied the influence of acquisition parameters on the T2 measurements. We examined if T2 changes in red bone marrow caused by the ablation of ex vivo trabecular bone were reversible and measured the patterns of heating and tissue damage. The technique was validated during the ablation of intact ex vivo bone samples and an in vivo animal model.ResultsResults of the calibration experiment showed a linear relationship (7 ms/°C) between T2 change and temperature and could be used to quantify the temperature during heating of up to 60 °C. During trabecular bone ablation, we observed a linear relationship (5.7 ms per °C) between T2 and temperature during the heating stage of the experiment. After cool down, there was residual T2 elevation (~35 ms) in the ablated area suggesting irreversible tissue changes. In ex vivo and in vivo cortical bone ablation experiments, we observed an increase in T2 values in the marrow adjacent to the intersection of the cortical bone and the beam path. The in vivo experiment showed excellent correspondence between the area of T2 elevation in marrow during the ablation and the resulting non-enhancing area in the post-contrast images.ConclusionsIn this study, we have demonstrated that T2-based thermometry can be used in vivo to measure the heating in the marrow during bone ablation. The ability to monitor the temperature within the bone marrow allowed more complete visualization of the heat distribution into the bone, which is important for local lesion control

Deer mandible tools: an examination of Oneota modified mandibles from La Crosse County, Wisconsin

This study focuses on the modified deer mandibles that have been recovered at late prehistoric Oneota sites over the last few decades by the M.V.A.C. in La Crosse County, Wisconsin. The purpose of this study is to clarify through experimentation the function of Oneota tools made from deer mandibles. Of the numerous deer mandibles and deer mandible fragments that have been recovered from Oneota context in the La Crosse locality there are a set of five deer mandibles, which show signs of heavy wear along the fracture of the bone marrow cavity where they were broken, presumably to obtain the marrow. These artifacts were found at the Pammel Creek site (47Lc61), the Valley View site (47Lc34), and the Gundersen Lutheran site (47Lc394), and the Sand Lake site (47Lc44). Experimental use demonstrated that the Oneota mandibles were identified as hide scrapers, which were used to soften leather for hide working

Structural basis of growth-related gain and age-related loss of bone strength

If bone strength was the only requirement of skeleton, it could be achieved with bulk, but bone must also be light. During growth, bone modelling and remodelling optimize strength, by depositing bone where it is needed, and minimize mass, by removing it from where it is not. The population variance in bone traits is established before puberty and the position of an individual's bone size and mass tracks in the percentile of origin. Larger cross-sections have a comparably larger marrow cavity, which results in a lower volumetric BMD (vBMD), thereby avoiding bulk. Excavation of a marrow cavity thus minimizes mass and shifts the cortex radially, increasing rigidity. Smaller cross-sections are assembled by excavating a smaller marrow cavity leaving a relatively thicker cortex producing a higher vBMD, avoiding the fragility of slenderness. Variation in cellular activity around the periosteal and endocortical envelopes fashions the diverse shapes of adjacent cross-sections. Advancing age is associated with a decline in periosteal bone formation, a decline in the volume of bone formed by each basic multicellular unit (BMU), continued resorption by each BMU, and high remodelling after menopause. Bone loss in young adulthood has modest structural and biomechanical consequences because the negative BMU balance is driven by reduced bone formation, remodelling is slow and periosteal apposition continues shifting the thinned cortex radially. But after the menopause, increased remodelling, worsening negative BMU balance and a decline in periosteal apposition accelerate cortical thinning and porosity, trabecular thinning and loss of connectivity. Interstitial bone, unexposed to surface remodelling becomes more densely mineralized, has few osteocytes and greater collagen cross-linking, and accumulates microdamage. These changes produce the material and structural abnormalities responsible for bone fragility