Bone morphogenetic protein-9 - An autocrine/paracrine cytokine in the liver

Bone morphogenetic proteins (BMPs) occupy important roles during developmen t serving to direct cells through specific differentiation programs. While several BMPs are essential for embryonic viability, their significance in m ediating intercellular communication in the context of adult organ systems remains largely unknown, In the adult rat we characterized the tissue-and c ell-specific transcription and translation of BMP-9, Utilizing a ribonuclea se protection assay, we determined that in the adult animal, BMP-9 expressi on occurs predominantly in the liver. Furthermore, we determined that the n on-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 conta in an abundance of immunoreactive BMP-9, Using [I-125]BMP-9, a receptor wit h specific binding affinity for BRBP-9 was characterized in primary culture s of hepatic endothelial cells and Kupffer cells. BMP-9 binding to these ce ll types was observed to be fully reversible and highly specific for this l igand, Additionally, we demonstrate that BMPP-9 is specifically internalize d 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 nonpa renchymal cells. Our results depict BMP-9 as a potential autocrine/paracrin e mediator in the hepatic reticuloendothelial system.