Sandbox Reserved 830: Difference between revisions

Oncostatin M, also called OSM, is encoded by the OSM gene and it is mostly produced in the end of the activation of macrophages and T cells. OSM belongs to the family of gp130 cytokines implying that it signals through the receptors containing gp130. OSM has been shown to have a lot of pleiotropic functions in cell proliferation, differentiation and inflammatory response. Thus, studies highlight its roles in cancer, bone and liver metabolism alteration, as well as in severe inflammatory disease, such as lung and skin inflammatory disease, atherosclerosis, cardiovascular diseases, and rheumatoid polyarthritis.

The AB loop is composed of <scene name='56/568028/Abloop_residues/1'>two α-helices from Pro43 to Arg46 and Glu59 to Gly64</scene>, while the residues in between pack closely and extensively against helix D. Comparatively, BC and CD loops are less stacking to the core. The BC loop located on the top of the four-helix bundle exhibits an important amount of B factors, along with several more classical secondary structures, which are a 3₁₀ <scene name='56/568028/Bcloops_helixes/1'>helix between residues Ala95 and Asp97 followed by the α helix up to Ser101</scene>.  

Activation of those pathways stimulates several responses. The main one is proliferation of a lot of different cell lines by increasing production of molecules, such as proliferation factors and metalloproteinase inhibitors.  In endothelial cells, vascular endothelial growth factors (VEGF) are secreted, promoting angiogenesis. Binding of OSM induces inhibition of other cell proliferation, like stem cells or tumor cells, by blocking the cell cycle in G2/M<ref name="three"> PMID: 10446061 </ref>. Binding of OSM grant an invasive phenotype of cells by stimulation of chemokine secretion (like eotaxin). Chemokine allows activation of immune cells as well, and then stimulates the production of antibodies<ref name="two"> PMID: 24381786 </ref>. Physiological function of OSM in the central nervous system remains unknown<ref group=""> PMID: 14985435 </ref>.

Defects in OSM and OSMR impact metastatic melanoma cell lines due to the PKC Δ-dependent phosphorylation of Ser 727 on STAT-3 and other signaling pathways. Moreover some epigenetic mechanisms have been shown to be responsible for altering the nature of metastatic melanoma, increasing OSMR expression and responsiveness of the cells<ref name="two"> PMID: 24381786 </ref>.  

Defects in OMS induce high levels of osteoblasts and osteoblast markers in differentiated osteosarcoma cells dramatically enhancing the proliferation of osteosarcoma cells, while stimulating an invasive phenotypic alteration of these cells mainly by the MMP-2 and VEGF expression, mediated by STAT3. <ref name="four"> PMID: 12218157 </ref>