scholarly journals A comparative study of the effects of genistein, estradiol and raloxifene on the murine skeletal system.

2009 ◽  
Vol 56 (2) ◽  
Author(s):  
Leszek Sliwiński ◽  
Joanna Folwarczna ◽  
Barbara Nowińska ◽  
Urszula Cegieła ◽  
Maria Pytlik ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Marrow ◽  
Mrna Expression ◽  
Bone Marrow Cells ◽  
Bone Mineralization ◽  
Mouse Bone Marrow ◽  
Skeletal System ◽  
Mouse Bone Marrow Cells

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.

The effect of decitabine on megakaryocyte maturation and platelet release

2011 ◽  
Vol 106 (08) ◽  
pp. 337-343 ◽  
Author(s):  
Jianhui Wang ◽  
Zanhua Yi ◽  
Shiyang Wang ◽  
Zongdong Li
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Bone Marrow Cells ◽  
Mouse Bone Marrow ◽  
Human Cord Blood ◽  
Primary Mouse ◽  
Platelet Release ◽  
Mouse Bone Marrow Cells ◽  
Marrow Cells

SummaryThrombocytopenia is a common feature of myelodysplastic syndromes (MDS). 5-aza-2’-deoxycytidine (decitabine) has been used to treat MDS with an approximately 20% response rate in thrombocytopenia. However, the mechanism of how decitabine increases platelet count is not clear. In this study, we investigated the effect of decitabine on megakaryocyte maturation and platelet release in the mouse. The effect of decitabine on megakaryocyte maturation was studied in an in vitro megakaryocyte differentiation model utilising mouse bone marrow cells and mouse megakaryoblastic cell line L8057. Decitabine (2.5 μM) is able to induce L8057 cells to differentiate into a megakaryocyte-like polyploidy cells with positive markers of acetylcholinesterase and αIIb integrin (CD41). Higher expression of αIIb integrin was also found in primary mouse bone marrow cells and human cord blood CD34+ cells cultured with both thrombopoietin and decitabine as compared to thrombopoietin alone. In addition, we noted a 30% platelet count increase in Balb/c mice 12 hours after the injection of decitabine at a clinically relevant dose (15 mg/m2), suggesting a rapid platelet release from the spleen or bone marrow. Our data suggest that decitabine increases platelet counts by enhancing platelet release and megakaryocyte maturation.

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