Origin of platelet-derived growth factor in megakaryocytes in guinea pigs.

Chernoff, Arthur; Levine, Rachmiel; Goodman, DeWitt S.

doi:10.1172/jci109747

Cited by 60 publications

(12 citation statements)

References 18 publications

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“…They are produced from the cytoplasm of the megakaryocyte. These precursors contain lysosomal enzymes [5] , ex-granules [6] platelet factor 4 [7], growth factors, [8] messenger RNA for platelet derived growth factor (PDGF) [9] and platelet antigens [10]. As all these factors are found in platelets these data suggest that platelet organelles and enzyme systems are created in the megakaryocyte.…”

Section: Introductionmentioning

confidence: 99%

The megakaryocyte platelet system and vascular disease

Brown

Martin

1994

Eur J Clin Investigation

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Platelets form a heterogeneous population of cells produced from the uniquely large polyploid cell found in the bone marrow, the megakaryocyte. The platelet megakaryocyte axis forms a dynamic equilibrium varying in normal biology and in disease. Prolonged platelet destruction leads to the production of large platelets from large, high ploidy megakaryocytes. In vivo and ex vivo studies show that such platelets have more haemostatic potential than smaller less dense platelets. The evidence suggesting that prothrombotic changes in the megakaryocyte platelet axis precede coronary artery thrombosis and the importance of platelet reactivity in atherosclerosis will be reviewed.

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Section: Introductionmentioning

confidence: 99%

The megakaryocyte platelet system and vascular disease

Brown

Martin

1994

Eur J Clin Investigation

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“…(J Histochem Cytochem 55:745-752, 2007) K E Y W O R D S bone morphogenetic proteins GATA-1 megakaryocytes osteoblasts osteosclerosis myelofibrosis BONE MARROW is an active site where osteogenic, hematopoietic, and immune cells interact and regulate hematopoiesis and bone remodeling in several, as yet incompletely, defined ways. Recent advances in understanding the role of different bone marrow cells in skeletal homeostasis have revealed that megakaryocytes (MKs) contain various growth factors and bone matrix proteins (Kacena et al 2006a) implicated in the process of bone remodeling and repair, such as bone morphogenetic proteins (BMPs) (Sipe et al 2004), transforming growth factor-b (TGF-b) (Fava et al 1990), fibroblast growth factor (FGF) (Martyre et al 1997), platelet-derived growth factor (PDGF) (Chernoff et al 1980;Wickenhauser et al 1995), osteocalcin (OC) (Thiede et al 1994), osteoprotegrin (OPG) (Chagraoui et al 2003), and vascular endothelial growth factor (VEGF) (Mohle et al 1997). Of the above growth factors/proteins, only BMPs have been shown to induce new ectopic bone formation in vivo (Wozney and Rosen 1998).…”

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confidence: 99%

Expression of Bone Morphogenetic Proteins and their Receptors in the Bone Marrow Megakaryocytes of GATA-1^low Mice

Garimella

Kacena

Tague

et al. 2007

J Histochem Cytochem.

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The mechanism of osteosclerosis associated with myelofibrosis in megakaryocyte (MK)-related myeloproliferative disorders is largely unknown. However, growth factors released from the bone marrow cells, including from MKs, have been implicated in myelofibrosis, osteosclerosis, and angiogenesis. GATA-1 is a transcription factor required for normal MK development. GATA-1 deficiency in mice (GATA-1low) leads to increased megakaryocytic proliferation, followed by osteosclerosis and myelofibrosis. In this study we investigated the expression of bone morphogenetic proteins (BMPs) and BMP receptors and their possible role in the development of osteosclerosis in the MKs of 12-month-old GATA-1low mice by immunohistochemistry, cytomorphometry, and quantitative real-time PCR. Marrow MKs from both wild-type and GATA-1low mice showed moderate to intense staining for BMP-2, −4, and −6 and BMPR-IA and BMPR-II, whereas splenic MKs showed no BMP immunostaining. Presence of BMP protein in the bone marrow of GATA-1low mice was more than that seen in controls, owing to an increased number of MKs and osteoblasts. The osteosclerosis seen in GATA-1low mice appeared not to be due to a reduced number of functional osteoclasts because the number of tartrate-resistant acid phosphatase-positive osteoclasts was greater in GATA-1low mice than in controls. Our findings demonstrate the presence of significant amounts of BMP-2, −4, and −6 along with their receptors in bone marrow MKs of WT and GATA-1low mice. The increased levels of BMPs appear to be a result of increased numbers of MKs in GATA-1low mice and may, in part, account for the stimulation of osteoblastic activity and resulting osteosclerosis.

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“…PDGF, a peptide isolated from outdated human platelets, has been shown to stimulate DNA synthesis in various tissues and cell systems (161)(162)(163)(164) and to stimulate collagen and noncollagen protein synthesis by arterial smooth muscle cells (165). PDGF was recently studied for its effects on bone formation in cultures of rat calvariae (166).…”

Section: Systemic Growth Factorsmentioning

confidence: 99%