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Paracrine Regulation (paracrine + regulation)
Selected AbstractsThe Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone ResorptionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2000Lorenz C. Hofbauer Abstract Although multiple hormones and cytokines regulate various aspects of osteoclast formation, the final two effectors are osteoprotegerin ligand (OPG-L)/osteoclast differentiation factor (ODF), a recently cloned member of the tumor necrosis factor superfamily, and macrophage colony,stimulating factor. OPG-L/ODF is produced by osteoblast lineage cells and exerts its biological effects through binding to its receptor, osteoclast differentiation and activation receptor (ODAR)/receptor activator of NF-,B (RANK), on osteoclast lineage cells, in either a soluble or a membrane-bound form, the latter of which requires cell-to-cell contact. Binding results in rapid differentiation of osteoclast precursors in bone marrow to mature osteoclasts and, at higher concentrations, in increased functional activity and reduced apoptosis of mature osteoclasts. The biological activity of OPG-L/ODF is neutralized by binding to osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF), a member of the TNF-receptor superfamily that also is secreted by osteoblast lineage cells. The biological importance of this system is underscored by the induction in mice of severe osteoporosis by targeted ablation of OPG/OCIF and by the induction of osteopetrosis by targeted ablation of OPG-L/ODF or overexpression of OPG/OCIF. Thus, osteoclast formation may be determined principally by the relative ratio of OPG-L/ODF to OPG/OCIF in the bone marrow microenvironment, and alterations in this ratio may be a major cause of bone loss in many metabolic disorders, including estrogen deficiency and glucocorticoid excess. That changes in but two downstream cytokines mediate the effects of large numbers of upstream hormones and cytokines suggests a regulatory mechanism for osteoclastogenesis of great efficiency and elegance. [source] Specificity of a new lipid mediator produced by testicular and peritoneal macrophages on steroidogenesisINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2000Lukyanenko Macrophage-derived factor (MDF) is a lipophilic factor produced by rat testicular and peritoneal macrophages that maximally stimulates testosterone production by rat Leydig cells through a steroidogenic acute regulatory protein independent mechanism. The purpose of the present study was to determine whether MDF is also produced by human macrophages, and/or if it acts on human steroidogenic cells. We also studied the tissue-specific functions of MDF by determining if it also acts on steroidogenic cells of the ovary and adrenal glands and, if so, does it require new protein synthesis. It was found that MDF was produced by human peritoneal macrophages, and was capable of stimulating human steroidogenic cells. In terms of tissue specificity, it was found that primary cultures of rat adrenocortical cells respond to MDF with increased secretion of aldosterone and corticosterone, as did rat granulosa cells by producing progesterone. MDF acted in the presence of cycloheximide, indicating that it does not require new protein synthesis. These results indicate that MDF may have significant therapeutic potential and provide a basis for future studies concerning its physiological role in humans. These results further suggest that MDF is not only involved in paracrine regulation of Leydig cells, but also has the potential for the local regulation of steroidogenesis in both granulosa and adrenal cortical cells. [source] An Insight to Pituitary Folliculo-Stellate CellsJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008S. Devnath Folliculo-stellate cells (FS-cells) are star-shaped and follicle-forming cells in the anterior pituitary gland that were first identified by electron microscopy as non-endocrine agranular cells. Light microscopy has revealed many of their cytophysiological features and the FS-cell is known to be positive for S-100 protein, a marker for FS-cells. So far, functions ascribed to FS-cells include the formation of an extensive and complex tridimentional network, scavenger activity by engulfing degenerated cells, paracrine regulation of endocrine cells by producing various growth factors and cytokines, such as interleukin-6, leukemia inhibitory factor, basic fibroblastic growth factor, vascular endothelial cell growth factor and follistatin, and large-scale inter-cellular communication by means of their long cytoplasmic processes and gap junctions. Moreover, their multi-potential characteristics and other cytological features support the possibility of them becoming organ-specific stem cells. This concept is yet to be resolved, however. In this review, we focus on these features of FS-cells along with some futuristic approaches. [source] In vivo delivery of fluoresceinated dextrans to the murine growth plate: Imaging of three vascular routes by multiphoton microscopyTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2006Cornelia E. Farnum Abstract Bone elongation by endochondral ossification occurs through the differentiation cascade of chondrocytes of cartilaginous growth plates. Molecules from the systemic vasculature reach the growth plate from three different directions: epiphyseal, metaphyseal, and a ring vessel and plexus associated with the perichondrium. This study is an analysis of the real-time dynamics of entrance of fluoresceinated tracers of different molecular weights into the growth plate from the systemic vasculature and tests the hypothesis that molecular weight is a key variable in the determination of both the directionality and the extent of tracer movement into the growth plate. Multiphoton microscopy was used for direct in vivo imaging of the murine proximal tibial growth plate in anesthetized 4- to 5-week-old transgenic mice with green fluorescent protein linked to the collagen II promoter. Mice were given an intracardiac injection of either fluorescein (332.3 Da) or fluoresceinated dextrans of 3, 10, 40, 70 kDa, singly or sequentially. For each tracer, directionality and rate of arrival, together with extent of movement within the growth plate, were imaged in real time. For small molecules (up to 10 kDa), vascular access from all three directions was observed and entrance was equally permissive from the metaphyseal and the epiphyseal sides. Within our detection limit (a few percent of vascular concentration), 40 kDa and larger dextrans did not enter. These results have implications both for understanding systemic and paracrine regulation of growth plate chondrocytic differentiation, as well as variables associated with effective drug delivery to growth plate chondrocytes. © 2005 Wiley-Liss, Inc. [source] Regulation of tumor dormancy as a function of tumor-mediated paracrine regulation of stromal Tsp-1 and VEGF expression,APMIS, Issue 7-8 2008SOO-YOUNG KANG Tumor dormancy is a critical yet poorly understood phenomenon affecting both the diagnosis and treatment of human cancers. This is due in large part to the lack of model systems available to study dormant tumor cells and the length of time needed to adequately examine the models that do exist. It has been demonstrated in several types of human cancer that tumor dormancy is a function of an impairment in angiogenesis. The intracellular signaling pathways regulating the expression of several pro- and anti-angiogenic proteins have been well characterized in human cancer cells. The intercellular signaling that takes place between tumor cells and the surrounding tumor-associated stroma has not been as extensively studied with regard to the regulation of angiogenesis, and as a result dormancy. In this review we define the key players in the regulation of angiogenesis and examine how their expression is regulated in the tumor-associated stroma. The resulting analysis is often seemingly paradoxical, underscoring the complexity of intercellular signaling within tumors and the need to better understand the environmental context underlying these signaling mechanisms. [source] Zinc ions in ,-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallographyAPMIS, Issue 12 2003L. G. SØNDERGAARD Zinc ions in the secretory granules of ,-cells are known to glue insulin molecules, creating osmotically stable hexamers. When the secretory granules open to the surface, the zinc ion pressure decreases rapidly and pH levels change from acid to physiological, which results in free insulin monomers and zinc ions. The released zinc ions have been suggested to be involved in a paracrine regulation of ,- and ,-cells. Since zinc is intimately involved in insulin metabolism and because zinc homeostasis is known to be disturbed in type 2 diabetes, we decided to study the ultrastructural localisation of zinc ions in insulin-resistant and type 2 diabetic rats as compared to controls. By means of autometallography, the only method available for demonstrating zinc ions at ultrastructural levels, we found zinc ions in the secretory granules and adjacent to the plasma membrane. The membrane-related staining outside the plasma membrane reflects release of zinc ions during exocytosis. No apparent difference was found in the ultrastructural localisation of zinc ions when we compared the obese Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK rats, representing type 2 diabetes, with controls. This suggests that the ultrastructural localisation of zinc ions is unaffected by the development of type 2 diabetes in rats in a steady state of glycaemia. [source] Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor ,,induced angiogenesis in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 9 2003Laura M. DeBusk Objective Rheumatoid arthritis (RA) is an inflammatory disease and an angiogenic disease. However, the molecular mechanisms promoting angiogenesis in RA are not clearly identified. Our objective was to study the role of an endothelium-specific receptor tyrosine kinase, Tie2, in angiogenesis of inflammatory arthritis. Methods Expression of Tie2 and its ligand, angiopoietin 1 (Ang1), in human synovium was examined by immunohistochemistry and Western blot. A novel synovium vascular window model was established to study the role of Tie2 in angiogenesis in vivo. Primary cultured endothelial cells and synoviocytes were used to study tumor necrosis factor , (TNF,),induced Tie2 and Ang1 expression. Results Tie2 was implicated in pathologic angiogenesis. We observed that Tie2 and Ang1 were elevated in human RA synovium. Using a novel collagen-induced arthritis synovial window model, we demonstrated that Tie2 signaling regulated arthritis angiogenesis in vivo. We also showed that Tie2 mediated TNF,-induced angiogenesis in a mouse cornea assay. In addition, we observed that TNF, can regulate Tie2 activation in multiple ways that may involve interactions between endothelial cells and synoviocytes. TNF, up-regulates Tie2 in endothelial cells through nuclear factor ,B, and it up-regulates Ang1 in synoviocytes. These findings suggest paracrine regulation of angiogenesis between endothelial cells and synoviocytes. Conclusion This study demonstrates that Tie2 regulates angiogenesis in inflammatory synovium. Tie2 signaling is an important angiogenic mediator that links the proinflammatory cytokine TNF, to pathologic angiogenesis. [source] | ||||||||||