Regulation of erythropoiesis in the erythroblast islands of the bone marrow

The review describes the mechanisms of interactions between regulatory systems in regulation of erythropoiesis in the erythroblast islands of the bone marrow.     

Effect of dexamethasone withdrawal on osteoblastic differentiation of bone marrow stromal cells

Dexamethasone is capable of directing osteoblastic differentiation of bone marrow stromal cells (BMSCs) in vitro, but its effects are not lineage-specific, and sustained exposure has been shown to down-regulate collagen synthesis and induce maturation of an adipocyte subpopulation within BMSC cultures. Such side effects might be reduced if dexamethasone is applied in a regimented manner, but the discrete steps in osteoblastic maturation that are stimulated by dexamethasone are not known. To examine this, dexamethasone was added to medium to initiate differentiation of rat BMSCs cultures and then removed after a varying number of days. Cell layers were analyzed for cell number, rate of collagen synthesis, expression of osteocalcin (OC), bone sialoprotein (BSP) and lipoprotein lipase (LpL), and matrix mineralization. Withdrawal of dexamethasone at 3 and 10 days was found to enhance cell number relative to continuous exposure, but did not affect to decrease collagen synthesis slightly. Late markers of osteoblastic differentiation, BSP expression and matrix mineralization, were also sensitive to dexamethasone and increased systematically with exposure while LpL systematically decreased. These results indicate that dexamethasone acts at both early and late stages to direct proliferative osteoprogenitor cells toward terminal maturation.     

Effect of dexamethasone on moesin gene expression in rabbit bone marrow stromal cells

The influence of dexamethasone on rabbit bone marrow stromal cells differentiation was studied by screening the action of dexamethasone on gene expression. Using differential display, we observed some differential amplifications. The use of five of thirteen different primers combination allowed to identify one or more differential bands. One of them was identified as moesin gene. Real-time PCR confirmed a significant reduction of moesin gene expression following dexamethasone treatment. The decrease of expression for this protein, involved in cytoskeletal organization, could explain the effects of dexamethasone treatment on bone marrow stromal cells differentiation.     

Mathematical model of the cytokinetics of erythropoiesis in mouse bone marrow and spleen]

The described model approximates the function of the erythropoietic system of the mouse to the function of a self-renewed cellular system, describable in the terms of cell population kinetics. The model is based on a number of experimentally proved ideas of contemporary haematology and arises from the assumption that there exists mutual negative influence between the cellular populations of the bone marrow and spleen. Considering the erythropoietic system in the mouse to be composed of two relatively independent parts - the bone marrow and spleen - the described model differs from the attempts so far made on the mathematical modelling of erythropoiesis.     

Gene expression profiling related to the enhanced erythropoiesis in mouse bone marrow cells

Peroxiredoxin II knockout (Prdx II(-/-)) mice had a spontaneous phenotype of hemolytic anemia. In this study, we found that Ter-119(+)CD71(+) cells increased in Prdx II(-/-) mice bone marrow (BM) at 8 weeks of age. We examined the differential expression profiles to bone marrow cells (BMCs) between Prdx II(+/+) and Prdx II(-/-) mice using a cDNA microarray. We identified the 136 candidates were differentially expressed a greater twofold increase or decrease than EPO receptor. In this study, we focused on the up-regulated NBPs during erythropoietic differentiation. According to cDNA microarray results, six NBPs except zfp-127 were up-regulated during erythropoiesis in Prdx II(-/-) mice. Among the six candidates, eIF3-p44, hnRNPH1, G3bp, and Zfpm-1 were dramatically increased at day 7 of the in vitro erythropoietic differentiation of human CD34(+) cells. However, DJ-1 and Rbm3 were slightly increased only at day 12. Our results suggest that up-regulated NBPs might be involved during erythropoietic differentiation.     

Cytological characteristics of erythropoiesis in thalassemia. I. Functional characteristics of the nucleated elements of erythropoiesis in the bone marrow

In 24 patients affected with thalassaemia of various degrees of seriousness the functional condition of nuclear cells or red serie was investigated in the bone-marrow. The investigation was carried out by analyzing partial erythroblastogrammes, evaluating proliferative activity according to the 3H-thymidine marking index and determining ineffective erythropoiesis by means of nucleated PAS-positive erythroblasts. The findings reveal the degree of seriousness of the disease being directly dependent on the extent of functional disturbances in the cells of the erythropoietic system.     

Effects of prostaglandins on erythropoiesis

A model has been presented for the role of the kidney in the physiologic and pathophysiologic control of erythropoiesis. It is postulated that an oxygen deficit created by anemia or hypobaric hypoxia results in the release of prostacyclin and its metabolite 6-keto PGE1, and the release of PGE2 with ischemic hypoxia. Prostacyclin, 6-keto-PGE1, or PGE2 activation of adenylate cyclase, an increase in cyclic AMP, activation of a protein kinase and the phosphorylation of hydrolases, which have been released from lysosomes by hypoxia, lead to increased biosynthesis of erythropoietin (Ep). The mechanism of labilization of lysosomes and the release of hydrolases from these cell organelles is postulated to be related to increases in cyclic GMP levels in a renal cell. An Ep-producing human renal carcinoma cell line grown in tissue culture has been demonstrated to produce significant amounts of PGE2. Meclofenamate, an inhibitor of prostaglandins synthesis, was found to inhibit in vitro production of PGE2, Ep, and dome formation in these renal carcinoma cells, giving support to our hypothesis that pathophysiologic production of Ep tumor cells depends upon prostaglandins production. An Ep-producing clone from this renal carcinoma cell line has been developed that contains low electron density (LED) cells after the cells reach confluency, which show a cytoplasm, with abundant and widely dilated endoplasmic reticulum, an oval nucleus, dispersed chromatin, and prominent nucleoli. These are the cells responsible for dome formation and Ep production. Non-EP-producing clones have also been produced from this renal carcinoma cell line, which did not produce domes even at high cell density and had a distinctly different cell type than the Ep-producing clone. Thus, it is postulated that prostacyclin (PGI2) and its metabolite 6-keto PGE1 play a significant role in hypoxic hypoxia stimulation of Ep production and PGE2 is involved in ischemic hypoxia and renal carcinoma cell production of Ep. A modulating effect of PGE2 and PGD2, the two primary bone marrow prostaglandins, has been proposed in Ep stimulation of the erythroid progenitor cell compartment (CFU-E and BFU-E).     

Effects of cyclic pressure on bone marrow cell cultures

The present in-vitro study used bone marrow cell cultures and investigated the effects of cyclic pressure on osteoclastic bone resorption. Compared to control (cells maintained under static conditions), the number of tartrate resistant acid phosphatase (TRAP)-positive, osteoclastic cells was significantly (p<0.05) lower when, immediately upon harvesting, bone marrow cells were exposed to cyclic pressure (10-40 kPa at 1.0 Hz). In contrast, once precursors in bone marrow cells differentiated into osteoclastic cells under static culture conditions for 7 days, subsequent exposure to the cyclic pressure of interest to the present study did not affect the number of osteoclastic cells. Most important, exposure of bone marrow cells to cyclic pressure for 1 h daily for 7 consecutive days resulted in significantly (p<0.05) lower osteoclastic bone resorption and in lowered mRNA expression for interleukin-1 (IL-1) and tumor necrosisfactor-a (TNF-a), cytokines that are known activators of osteoclast function. In addition to unique contributions to osteoclast physiology, the present study provided new evidence of a correlation between mechanical loading and bone homeostasis as well as insight into the molecular mechanisms of bone adaptation to mechanical loading, namely cytokine-mediated control of osteoclast functions.     

The content of ribonucleoproteids in the bone marrow erythroblastic islands in various functional states of erythropoiesis

Erythroblastic islands of the bone marrow are morpho-fuctional units of erythropoiesis. The functional state of the erythroblastic islands' erythrokariocytes and central macrophages of the bone marrow was first studied by estimation of the content of ribonucleoproteids in its cells (Brashe reaction). Acute blood loss and posttransfusion polycytemia lead to enhancement of the content of ribonucleoproteids in erythrokariocytes and central macrophages of the bone marrow of the rates.