EPO treatment in the 5T33MM mice resulted in a 50% (p?

EPO treatment in the 5T33MM mice resulted in a 50% (p?Mouse monoclonal to FAK problems are common. Imbalanced bone redesigning in the myeloma BM is PhiKan 083 definitely caused by improved osteoclast activity, together with reduced osteoblast function. MM cells homing to the BM are believed to exert a major catabolic effect mediated by numerous relationships with stromal cells, leading to recruitment, differentiation and activation of osteoclast progenitors within the BM and inhibition of osteogenesis25,26. The crosstalk between the hematological/immune and bone systems in MM and their response to EPO treatment are, as yet, not completely resolved. Monocyte differentiation into osteoclasts (the bone resorbing PhiKan 083 cells) is definitely driven and controlled from the receptor activator for nuclear element kappa PhiKan 083 B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis27. RANKL is the main pro-osteoclastogenic cytokine, and it is antagonized by OPG. Myeloma plasma cells communicate RANKL and induce an imbalance in the RANKL/OPG relationships, resulting in improved osteoclastic activation and bone resorption25,26. EPO effects on bone may depend on pathophysiological conditions. EPO supported bone formation in fracture healing models e.g.28, while, it induced bone loss in adult mice29,30,31. Our recent findings that EPO directly stimulates bone loss activation of EPO-R signaling in the monocytic lineage30, coupled with the central part of macrophages in MM32, focus on the need to determine EPO effect on bone in the context of MM. The 5T33MM mouse model originates from spontaneously developed MM in seniors mice of the C57BL/KalwRij strain33. The clinical characteristics of this model, including the selective localization of the MM cells in the BM and elevated serum monoclonal immunoglobulin IgG2b Kappa (IgG2b), are similar to those of human being myeloma34,35, rendering it a useful model for studying MM and relevant restorative approaches. The absence of severe bone disease in the 5T33 MM model36,37 serves well the purpose of screening EPO effects on bone. It allows separation of the bone disease due to MM from your EPO effects. One can very easily conclude what would happen in individuals with MM showing bone diseases who are treated with EPO for his or her anemia. Here we display that in 5T33MM, EPO functions as a double-edged sword, by improving immune parameters on one hand, yet accelerating bone.

Related Posts