The relationship between bone marrow adipose tissue and bone metabolism in postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) is a prevalent skeletal disorder associated with menopause-related estrogen withdrawal. PMOP is characterized by low bone mass, deterioration of the skeletal microarchitecture, and subsequent increased susceptibility to fragility fractures, thus contributing to disability and mortality. Accumulating evidence indicates that abnormal expansion of marrow adipose tissue (MAT) plays a crucial role in the onset and progression of PMOP, in part because both bone marrow adipocytes and osteoblasts share a common ancestor lineage. The cohabitation of MAT adipocytes, mesenchymal stromal cells, hematopoietic cells, osteoblasts and osteoclasts in the bone marrow creates a microenvironment that permits adipocytes to act directly on other cell types in the marrow. Furthermore, MAT, which is recognized as an endocrine organ, regulates bone remodeling through the secretion of adipokines and cytokines. Although an enhanced MAT volume is linked to low bone mass and fractures in PMOP, the detailed interactions between MAT and bone metabolism remain largely unknown. In this review, we examine the possible mechanisms of MAT expansion under estrogen withdrawal and further summarize emerging findings regarding the pathological roles of MAT in bone remodeling. We also discuss the current therapies targeting MAT in osteoporosis. A comprehensive understanding of the relationship between MAT expansion and bone metabolism in estrogen deficiency conditions will provide new insights into potential therapeutic targets for PMOP.     

The relationship between 59Fe uptake in marrow and 239Pu deposition in bone.

The marrow in the left femur of each of 17 mice was destroyed by X-irradiation and 59Fe and 239Pu uptake into both femurs was measured 1, 3 and 7 days later. Uptake of 59Fe into marrow was depressed in the left femur 1 and 3 days after irradiation but was enhanced in the right unirradiated femur 3 days after the left femur was irradiated. There was no corresponding depression of 239Pu uptake into the left irradiated femur or enhancement into the right unirradiated femur. These results do not support the view that a functioning erythropoietic marrow is necessary for 239Pu to be deposited in bone.     

Correction: Hepatitis B virus infection and replication in human bone marrow mesenchymal stem cells

ABSTRACT: Correction After publication of this work (Virol J 2011, 8:486), we noted that D of Figure 1 was incorrect. Now the correct figure has been provided with this correction.     

Pluripotential stem cell replication in continuous human, prosimian, and murine bone marrow culture

Prolonged replication of pluripotential stem cells and committed progenitor cells is sustained for prolonged periods in a murine marrow culture system. Alterations in stem cell replication and differentiation are observed after infection of the cultures with Friend virus and Kirsten sarcoma virus consistent with transformation of pluripotential stem cells in the first case and transformation of the macrophage component of the hemopoietic microenvironment in the second. Prolonged myelopoiesis and CFU-c proliferation was also observed in continuous human and prosimian marrow cultures, suggesting the applicability of this technique for analysis of stem cell control and in vitro leukemogenesis in species other than the mouse.     

The CD24 antigen discriminates between pre-B and B cells in human bone marrow.

When bone marrow (BM) lymphoid cells from 12 adult healthy donors were labeled by CD24 antibodies and analyzed by flow cytometry, two positive populations of cells were demonstrated in each sample (by a separated bimodal specific immunofluorescence). One population had intermediate CD24-Ag density (termed CD24+ cells) whereas the other had high CD24-Ag density (termed CD24(2+) cells). CD24+ cells represented 5.8 +/- 2.7% of the total lymphoid BM cells and CD24(2+) cells 5.6 +/- 2.5%. Using dual fluorescence analysis on eight samples, all CD24+ cells expressed the CD21 and CD37 mature B cell Ag and also surface IgM (sIgM), but this population lacked CD10 Ag. These cells also expressed CD19 Ag, and at a higher density than CD24(2+) cells. They were also positive for HLA-DR Ag. Conversely, CD24(2+) cells were shown to be early cells of the B cell lineage. While all the CD24(2+) cells were HLA-DR+ and CD19+, 64 +/- 16% of them expressed CD20 Ag (at a lower density than CD24+ cells), 65 +/- 21% CD10 Ag, and 22 +/- 8% were positive for cytoplasmic mu-chains (c mu). None of these cells expressed the CD21 and CD37 mature B cell Ag or sIgM. Additional experiments on four different healthy donors demonstrated that 30 +/- 9% of the CD24(2+) cells expressed the CD34 Ag and that the CD24+ cells did not express it. Thus, the CD24 Ag permits discrimination between two populations of the B cell lineage present in adult BM: 1) A CD24(2+) cell population including "pre" pre-B cells (HLA-DR+, CD19+, CD10+/-, CD20-, CD21-, CD34+, CD37-, c mu-), "intermediate" pre-B cells (HLA-DR+, CD19+, CD10+, CD20+, CD21-, CD34-, CD37-, c mu-), and "true" pre-B cells (HLA-DR+, CD19+, CD10+, CD20+, CD21-, CD34-, CD37-, c mu+). 2) A CD24+ cell population including B cells of the standard phenotype (HLA-DR+, CD19+, CD10-, CD20+, CD21+, CD34-, CD37+, c mu-, sIgM+).     

Genetic markers in human bone marrow transplantation.

Blood cell isozymes, red cell antigens, immunoglobulin allotypes, and marker chromosomes are suitable tools to monitor bone marrow engraftment and marrow graft quality. Data on genetic markers from 26 patients who underwent bone marrow transplantation as a treatment for acute leukemia are presented here.     

Immunotoxin-mediated elimination of clonogenic tumor cells in the presence of human bone marrow

An immunotoxin was synthesized with pokeweed antiviral protein and an IgG1 monoclonal antibody directed against human B and pre-B cells. The B43 murine monoclonal antibody does not react with normal human bone marrow precursor cells. The immunotoxin bound to all Burkitt's lymphoma cell lines that were tested but not to human peripheral blood T cells. The ability of antibody-toxin conjugate to inhibit human lymphoblast cell lines was checked in a clonogenic assay system. The immunotoxin in the presence of chloroquine elicited 5.8 logs of killing of Burkitt's lymphoma cells (B-ALL). The efficient inhibition of clonogenic growth of B-ALL cells was not affected by the presence of normal bone marrow cells. The immunotoxin was not very toxic to pluripotent stem cells; less than 50% of the stem cells were lost under conditions where 5.6 logs of clonogenic lymphoma cells were eliminated from a 100-fold excess of normal marrow cells. Further, when assayed by long-term human bone marrow cultures, immunotoxin treatment did not result in a significant loss of pluripotent precursor cells.     

Antigenic relationship between bone marrow lymphocytes cortical thymocytes and a subpopulation of peripheral T cells in the rat: description of a bone marrow lymphocyte antigen.

Populations of rat bone marrow lymphocytes (BML) consisting of approximately 90 percent, “tnull” cells were prepared by density gradient centrifugation, passage through a column of fine glass beads, and treatment with anti-T cell and anti-B cell serum plus complement. Antisera to these bone marrow lymphocytes were raised in rabbits. After absorption with RBC and peritoneal exudate cells, the anti-BML sera were found by immunofluorescence to react selectively with “null” cells in bone marrow, with cortical thymocytes, and with a cortisone-sensitive subset of T cells in blood and in spleen, possibly in red pulp. The antigen that is common to these cell types is designated the rat bone marrow lymphocyte antigen (RBMLA). Lymphocytes that are positive fur KBMLA are negative for another lymphocyte-specific heteroantigen, rat musked thymocyte antigen (RMTA). As shown previously, RMTA is present on medullary thymocytes and ou cortisone-resistant T cells in white pulp of spleen, paracortex of lymph node and thoracic duct lymph. It is postulated that two developmentally and functionally distinct lines of T cells exist in peripheral lymphoid tissues of the rat, one derived from cortical thymocytes and one derived from medullary thymocytes. It is further postulated that the “null” population of bone marrow lymphocytes contains the lymphopoietic stem cells from which these two lines of T cells originate.     

人类疱疹病毒8型与非KS肿瘤的研究进展

人类疱疹病毒8型(Human herpesvirus-8,HHV-8)又名Kaposi肉瘤相关疱疹病毒(Kaposi's sarcoma-associaled herpesvirus,KSHV),属Rhadino病毒或者γ-2疱疹病毒,与γ-1疱疹病毒、EB病毒(EBV)同属人类γ疱疹病毒,是由Chang等在1994年采用代表性差异分析法从一例AIDS-KS患者的病变组织中发现的一种新病毒.随着对HHV-8及其亚型的深入研究,其与非Ks肿瘤的关系也逐渐引起了各国学者的关注.近年来大量研究表明其与非KS肿瘤疾病的关系密切.     

5-methyltetrahydrofolate homocysteine cobalamin methyltransferase in human bone marrow and its relationship to pernicious anemia

Dialyzed extracts from human bone marrow catalyze [5-¹⁴C]methyltetrahydrofolate homocysteine transmethylation at slow but significant rates which can be detected by using substrate with a very high specific radioactivity. Enzymatic activity is associated with nucleated marrow cells rather than mature, nondividing erythrocytes. Extract transmethylase activities in 15 marrow specimens from patients without B-12 deficiency ranged from 157–1020 pmoles of [Me-¹⁴C]methionine formed/hr/10⁷ nucleated cells. Catalysis is dependent on S-adenosyl-l-methionine and a flavin-reducing system, typical for the presence of a cobalamin (B-12) methyltransferase. No in vitro requirement for exogenous B-12 was observed except for the marrow extracts from two patients known to be B-12 deficient. One of these extracts was markedly stimulated by methyl-B-12 indicative that mostly apomethyltransferase was present. These tracer assays with cell-free extracts provide the first direct evidence that human bone marrow contains B-12 methyltransferase; they also afford further evidence for a 5-methyltetrahydrofolate trap in B-12 deficiency with its associated megaloblastic anemia. In addition, we have observed that in normal peripheral blood leukocytes the mononuclear fraction contains 10–30 times as much B-12 methyltransferase per nucleated cell as the polymorphonuclear granulocyte fraction.     

The relationship between DNA replication and chromosome structure

Summary The results obtained by acridine orange staining of chromosomes, after BrdU treatment, during one or two cell cycles, are described. The alterations of chromosome structure do not depend only on BrdU incorporation into DNA. Some other mechanisms are necessarily involved, and it is postulated that they are disturbances of protein-DNA association, occurring in G₁ and in S- or G₂-phase. The aspect of metaphase chromosomes then appears as the result of several metabolic steps, all occurring during interphase.Presented at the Fifth Meeting of the Cytogenetics Section of the Society for Anthropology and Human Genetics, Basel, Switzerland, June 17–19, 1976.     

Mapping bone marrow niches of disseminated tumor cells

Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell (HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.     

Lipid composition of human bone marrow

1. A modified method for the analysis of phospholipid mixtures by selective hydrolysis is described. 2. The phospholipid compositions of normal human bone marrow and of the bone marrows of patients who died with anaemia or various forms of leukaemia were investigated. 3. Phospholipids from normal bone marrow comprised about 44% of lecithin, 4% of choline plasmalogen, 7% of glyceryl ether phospholipid (choline base), 10% of sphingomyelin, 22% of phosphatidylethanolamine plus phosphatidylserine, 8% of ethanolamine plasmalogen and 5% of glyceryl ether phospholipid (ethanolamine base). 4. The proportion of kephalin (i.e. phosphatidylethanolamine plus phosphatidylserine) in the pathological bone marrows tended to be lower than normal. No other consistent differences were observed between the normal and pathological samples. 4. A ceramide dihexoside was isolated from normal bone marrow.     

Immunoreconstitution after human bone marrow transplantation

Immunologic reconstitution was studied in 24 patients who underwent bone marrow transplantation, 17 allogenic and 7 autologous. The GVHD prophylaxis consisted of methotrexate and prednisone. The complete immune evaluation was to be carried out prior to transplantation at 1, 2, 3, 6, 9, 12 months after BMT and subsequently every 6 months up to 4 years. The investigated immunological parameters included total lymphocyte count, B-lymphocytes, T3-, T4-, T8-lymphocytes, T4/T8 ratio, natural killer cell activity, ADCC, lymphocyte blastogenic response and serum-IgG, -IgA, -IgM. Absolute lymphocyte count, B-lymphocytes, T3-lymphocytes recovered to normal levels after 6 months. T4-lymphocytes decreased significantly during the first 180 days posttransplant. T8-lymphocytes increased after 6 months to values higher than normal and the T4/T8 ratio decreased significantly and continued below 0.8 for 48 months. Patients without and with GVHD had low lymphocyte response to PHA and Con A for the first 6 months.