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Erythropoietin (EPO) primarily regulates red blood cell formation, and EPO serum levels are increased on hypoxic stress (e.g., anemia and altitude). In addition to anemia, recent discoveries suggest new therapeutic indications for EPO, unrelated to erythropoiesis. We investigated the skeletal role of EPO using several models of overexpression (Tg6 mice) and EPO administration (intermittent/continuous, high/low doses) in adult C57Bl6 female mice. Using microcomputed tomography, histology, and serum markers, we found that EPO induced a 32%-61% trabecular bone loss caused by increased bone resorption (+60%-88% osteoclast number) and reduced bone formation rate (-19 to -74%; P < 0.05 throughout). EPO targeted the monocytic lineage by increasing the number of bonemonocytes/macrophages, preosteoclasts, and mature osteoclasts. In contrast to the attenuated bone formation in vivo, EPO treatment in vitro did not inhibit osteoblast differentiation and activity, suggesting an indirect effect of EPO on osteoblasts. However, EPO had a direct effect on preosteoclasts by stimulating osteoclastogenesis in isolated cultures (+60%) via the Jak2 and PI3K pathways. In summary, our findings demonstrate that EPO negatively regulates bone mass and thus bears significant clinical implications for the potential management of patients with endogenously or therapeutically elevated EPO levels. [ABSTRACT FROM AUTHOR]

Deals with a study which assessed the impact of matrix metalloproteinases (MMP) deficiencies in in vivo and in vitro models of angiogenesis. In vivo activation of the MMP-9 promoter of host cells in tumor transplants; Effect of MMP-9 and MMP-3 deficiency on tumor invasion and vascularization; Effect of the combined deficiency of MMP-2 and MMP-9 on tumor invasion and vascularization.

Investigates the expression and activities of matrix metalloproteinase (MMP) 2 and MMP-9 gelatinase in the course of laser-induced murine choroidal neovascularization. Gelatin zymography analysis of ocular posterior segments; Fluorescein angiography performed before death; Role of MMP during the early phases of choroidal neovascularization.