Bone morphogenetic proteins (BMPs) occupy important roles during development serving to direct cells through specific differentiation programs. While several BMPs are essential for embryonic viability, their significance in mediating intercellular communication in the context of adult organ systems remains largely unknown. In the adult rat we characterized the tissueand cell-specific transcription and translation of BMP-9. Utilizing a ribonuclease protection assay, we determined that in the adult animal, BMP-9 expression occurs predominantly in the liver. Furthermore, we determined that the non-parenchymal cells of the liver, i.e. endothelial, Kupffer, and stellate cells, are the major sources of this message. Western analyses corroborate the ribonuclease protection assay results, confirming that LEC and KC contain an abundance of immunoreactive BMP-9. Using [ 125 I]BMP-9, a receptor with specific binding affinity for BMP-9 was characterized in primary cultures of hepatic endothelial cells and Kupffer cells. BMP-9 binding to these cell types was observed to be fully reversible and highly specific for this ligand. Additionally, we demonstrate that BMP-9 is specifically internalized upon binding to its receptor. This may represent a novel BMP receptor and is the first to be characterized in primary cultures of mature liver nonparenchymal cells. Our results depict BMP-9 as a potential autocrine/paracrine mediator in the hepatic reticuloendothelial system.The secreted proteins of the transforming growth factor- (TGF-) 1 superfamily occupy central roles in cellular differentiation and growth. Members of this cytokine superfamily represent a highly conserved set of signaling proteins whose analogs are distributed widely in organisms from Drosophila melanogaster to Homo sapiens. A specific subclassification within the TGF- superfamily comprises the bone morphogenetic proteins (BMPs). These secreted, dimeric proteins were characterized originally by their ability to induce ectopic bone formation following subdermal injection (1, 2). Generalizing from the available literature, it appears that BMP signaling is important to an organism during development and/or growth. For example, BMP-2 knockout mice expire in utero with numerous developmental lesions on extra-embryonic and embryonic structures (3). Mice deficient for BMP-7 die soon after birth exhibiting several bone and soft tissue abnormalities which include underdeveloped kidneys that lack glomeruli (4). BMP-5 knock-outs are healthy yet sustain many skeletal and soft tissue defects including but not limited to, loss of one pair of ribs, a smaller external ear, and a reduced ability to repair rib fractures (5). These phenotypes arise when the affected tissues are undergoing morphogenesis suggesting that BMP signaling is particularly relevant during development when cells are being directed toward specific differentiation pathways.BMPs and their receptors are expressed in numerous cell types and during many different stages of embryonic development and adult life (6,...
In 1629 Sir George Calvert, the first Lord Baltimore, was at a crossroads in his life. He departed his fledgling colony in Ferryland, Newfoundland for the warmer climes of Virginia, entertaining the possibility of a new colonial venture in the Chesapeake. Although Sir George would not live to see the arrival of his settlers in Maryland in 1634, the colony was very much the culmination of his efforts and experiences. This paper examines a previously unpublished letter from George Calvert to his close friend Sir Thomas Wentworth on the eve of his departure from Newfoundland. The document contains important insights on Calvert's first New World venture and illustrates how Ferryland and the subsequent grant of the proprietary Province of Avalon were inexorably linked, both by family and design, to Maryland.
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