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The Journal of Clinical Endocrinology... Mar 2021Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut... (Review)
Review
Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi, and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanisms include absorption and diffusion of bacterial metabolites, such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.
Topics: Animals; Bone Development; Bone Marrow; Bone Marrow Cells; Bone Remodeling; Bone and Bones; Gastrointestinal Microbiome; Humans; Parathyroid Hormone
PubMed: 33254225
DOI: 10.1210/clinem/dgaa895 -
Hormone Molecular Biology and Clinical... Oct 2016White adipose tissue (WAT) is a major endocrine organ, secreting a diverse range of hormones, lipid species, cytokines and other factors to exert diverse local and... (Review)
Review
White adipose tissue (WAT) is a major endocrine organ, secreting a diverse range of hormones, lipid species, cytokines and other factors to exert diverse local and systemic effects. These secreted products, known as 'adipokines', contribute extensively to WAT's impact on physiology and disease. Adipocytes also exist in the bone marrow (BM), but unlike WAT, study of this bone marrow adipose tissue (MAT) has been relatively limited. We recently discovered that MAT contributes to circulating adiponectin, an adipokine that mediates cardiometabolic benefits. Moreover, we found that MAT expansion exerts systemic effects. Together, these observations identify MAT as an endocrine organ. Additional studies are revealing further secretory functions of MAT, including production of other adipokines, cytokines and lipids that exert local effects within bone. These observations suggest that, like WAT, MAT has secretory functions with diverse potential effects, both locally and systemically. A major limitation is that these findings are often based on in vitro approaches that may not faithfully recapitulate the characteristics and functions of BM adipocytes in vivo. This underscores the need to develop improved methods for in vivo analysis of MAT function, including more robust transgenic models for MAT targeting, and continued development of techniques for non-invasive analysis of MAT quantity and quality in humans. Although many aspects of MAT formation and function remain poorly understood, MAT is now attracting increasing research focus; hence, there is much promise for further advances in our understanding of MAT as an endocrine organ, and how MAT impacts human health and disease.
Topics: Adipose Tissue; Animals; Bone Marrow; Endocrine System; Humans
PubMed: 27149203
DOI: 10.1515/hmbci-2016-0012 -
Arteriosclerosis, Thrombosis, and... Jan 2021Until recently, immunologic memory was considered an exclusive characteristic of adaptive immunity. However, recent advances suggest that the innate arm of the immune... (Review)
Review
Until recently, immunologic memory was considered an exclusive characteristic of adaptive immunity. However, recent advances suggest that the innate arm of the immune system can also mount a type of nonspecific memory responses. Innate immune cells can elicit a robust response to subsequent inflammatory challenges after initial activation by certain stimuli, such as fungal-derived agents or vaccines. This type of memory, termed trained innate immunity (also named innate immune memory), is associated with epigenetic and metabolic alterations. Hematopoietic progenitor cells, which are the cells responsible for the generation of mature myeloid cells at steady-state and during inflammation, have a critical contribution to the induction of innate immune memory. Inflammation-triggered alterations in cellular metabolism, the epigenome and transcriptome of hematopoietic progenitor cells in the bone marrow promote long-lasting functional changes, resulting in increased myelopoiesis and consequent generation of trained innate immune cells. In the present brief review, we focus on the involvement of hematopoietic progenitors in the process of trained innate immunity and its possible role in cardiometabolic disease.
Topics: Bone Marrow; Cardiovascular Diseases; Hematopoietic Stem Cells; Humans; Immunity, Innate; Immunologic Memory; Metabolic Diseases; Myelopoiesis
PubMed: 33207931
DOI: 10.1161/ATVBAHA.120.314215 -
Metabolism: Clinical and Experimental Feb 2017The bone marrow niche is composed of cells from hematopoietic and mesenchymal origin. Both require energy to power differentiation and these processes are intimately... (Review)
Review
The bone marrow niche is composed of cells from hematopoietic and mesenchymal origin. Both require energy to power differentiation and these processes are intimately connected to systemic metabolic homeostasis. Glycolysis is the preferred substrate for mesenchymal stromal cells in the niche, although fatty acid oxidation and glutaminolysis are important during stage specific differentiation. Autophagy and lipophagy, in part triggered by adenosine monophosphate-activated protein kinase (AMPK), may also play an important but temporal specific role in osteoblast differentiation. Enhanced marrow adiposity is caused by clinical factors that are genetically, environmentally, and hormonally mediated. These determinants mediate a switch from the osteogenic to the adipogenic lineage. Preliminary evidence supports an important role for fuel utilization in those cell fate decisions. Although both the origin and function of the marrow adipocyte remain to be determined, and in some genetic mouse models high marrow adiposity may co-exist with greater bone mass, in humans changes in marrow adiposity are closely linked to adverse changes in skeletal metabolism. This supports an intimate relationship between bone and fat in the marrow. Future studies will likely shed more light on the relationship of cellular as well as whole body metabolism on the ultimate fate of bone marrow stromal cells.
Topics: Adipocytes; Adiposity; Animals; Bone Density; Bone Marrow; Bone and Bones; Energy Metabolism; Humans; Osteoblasts
PubMed: 28081773
DOI: 10.1016/j.metabol.2016.11.013 -
Frontiers in Immunology 2022
Topics: Bone Marrow; Bone Marrow Cells; Cell Count
PubMed: 36119043
DOI: 10.3389/fimmu.2022.1019489 -
Nature Reviews. Immunology Dec 2011Progenitor cells that are the basis for all blood cell production share the bone marrow with more mature elements of the adaptive immune system. Specialized niches... (Review)
Review
Progenitor cells that are the basis for all blood cell production share the bone marrow with more mature elements of the adaptive immune system. Specialized niches within the bone marrow guide and, at times, constrain the development of haematopoietic stem and progenitor cells (HSPCs) and lineage-restricted immune progenitor cells. Specific niche components are organized into distinct domains to create a diversified landscape in which specialized cell differentiation or population expansion programmes proceed. Local cues that reflect the tissue and organismal state affect cellular interactions to alter the production of a range of cell types. Here, we review the organization of regulatory elements in the bone marrow and discuss how these elements provide a dynamic means for the host to modulate stem cell and adaptive immune cell responses to physiological challenges.
Topics: Animals; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Hematopoietic Stem Cells; Humans; Immunity; Stem Cell Niche
PubMed: 22193770
DOI: 10.1038/nri3132 -
Blood Sep 2014
Topics: Adenocarcinoma; Bilirubin; Biopsy; Bone Marrow; Humans; Intestinal Neoplasms; Male; Middle Aged; Necrosis
PubMed: 25379599
DOI: 10.1182/blood-2013-10-462804 -
The British Journal of Radiology Feb 2023Normal marrow contains both hematopoietic/red and fatty/yellow marrow with a predictable pattern of conversion and skeletal distribution on MRI. Many variations in... (Review)
Review
Normal marrow contains both hematopoietic/red and fatty/yellow marrow with a predictable pattern of conversion and skeletal distribution on MRI. Many variations in normal bone marrow signal and appearances are apparent and the reporting radiologist must differentiate these from other non-neoplastic, benign or neoplastic processes. The advent of chemical shift imaging has helped in characterising and differentiating more focal heterogeneous areas of red marrow from marrow infiltration. This review aims to cover the MRI appearances of normal marrow, its evolution with age, marrow reconversion, variations of normal marrow signal, causes of oedema-like marrow signal, and some common non-neoplastic entities, which may mimic marrow neoplasms.
Topics: Humans; Bone Marrow; Magnetic Resonance Imaging
PubMed: 35522786
DOI: 10.1259/bjr.20220063 -
Molecular Genetics and Metabolism 2015Myelodysplastic syndromes (MDS) are characterized by cytopenias resulting from ineffective hematopoiesis with a predisposition to transform to acute myeloid leukemia... (Review)
Review
Myelodysplastic syndromes (MDS) are characterized by cytopenias resulting from ineffective hematopoiesis with a predisposition to transform to acute myeloid leukemia (AML). Recent evidence suggests that the hematopoietic stem cell microenvironment contributes to the pathogenesis of MDS. Inflammation and hypoxia within the bone marrow are key regulators of hematopoietic stem and progenitor cells that can lead to several bone marrow failure syndromes, including MDS. In this brief review, we provide an overview of the clinical and molecular features of MDS, the bone marrow microenvironment, and specific pathways that lead to abnormal blood cell development in MDS. Characterization of key steps in the pathogenesis of MDS will lead to new approaches to treat patients with this disease.
Topics: Animals; Bone Marrow; Cellular Microenvironment; Hematopoiesis; Humans; Mesenchymal Stem Cells; Myelodysplastic Syndromes
PubMed: 26210353
DOI: 10.1016/j.ymgme.2015.07.004 -
Cell Reports Jul 2019The bone marrow microenvironment is composed of heterogeneous cell populations of non-hematopoietic cells with complex phenotypes and undefined trajectories of...
The bone marrow microenvironment is composed of heterogeneous cell populations of non-hematopoietic cells with complex phenotypes and undefined trajectories of maturation. Among them, mesenchymal cells maintain the production of stromal, bone, fat, and cartilage cells. Resolving these unique cellular subsets within the bone marrow remains challenging. Here, we used single-cell RNA sequencing of non-hematopoietic bone marrow cells to define specific subpopulations. Furthermore, by combining computational prediction of the cell state hierarchy with the known expression of key transcription factors, we mapped differentiation paths to the osteocyte, chondrocyte, and adipocyte lineages. Finally, we validated our findings using lineage-specific reporter strains and targeted knockdowns. Our analysis reveals differentiation hierarchies for maturing stromal cells, determines key transcription factors along these trajectories, and provides an understanding of the complexity of the bone marrow microenvironment.
Topics: Bone Marrow; Cell Differentiation; Humans; Stem Cell Niche
PubMed: 31291568
DOI: 10.1016/j.celrep.2019.06.031