Regulation of thrombopoietin in bone marrow

The normal elimination of a large number of circulating hematopoietic cells from the circulation each day necessitates substantial proliferation and maturation of progenitor cells in bone marrow. An impressive array of cytokines and growth factors help to manage these complicated processes in order to maintain a physiologically appropriate number of each of the various blood cell types. Thrombopoietin is one such factor that is important for the platelet lineage. In addition, thrombopoietin participates in sustaining pluripotent stem cells and early multi-lineage progenitors. In the following report, we have chosen to focus on the prior characteristic. It has been observed that the expression of thrombopoietin message is regulated differently in different parts of the body. Although thrombopoietin is highly expressed in the liver its expression is largely unregulated; however, a significant up-regulation is observed in bone marrow. Therefore, bone marrow stromal cells as wells as a suitable cell model were subjected to treatment with serum and platelet extracts. The primary effect of both the platelet derived and non-platelet derived serum components was to down-modulate thrombopoietin message levels indicating that any physiological increase in TPO expression is likely the result of a decrease of inhibitory factors rather than an increase in a stimulatory factor. Serum was also capable of depressing TPO protein secretion. A series of reported gene constructs based on the TPO gene demonstrated that the mechanism responsible for at least a portion of the serum suppression was transcriptional repressio