Therefore, it stands to reason that E may use this mechanism to regulate ErbB3 action in perinatal ovary cells during primordial folliculogenesis. The differential expression as well as spatial localization of EBP1 in ovary cells during primordial follicle formation suggests that EBP1 as a downstream regulatory protein may modulate the effect of proteins that play critical role in the differentiation of ovarian somatic cells. Further, E regulation of EBP1 expression depends on the availability of ESR1 and hormonal priming of ovarian cells. We speculate that EBP1 may also regulate ESR1 levels in differentiating ovarian somatic cells. The well established ability of total joint implants to restore function and mobility has been recently shocked by the unexpected early failures of some artificial hip implants. These failures are attributed to excessive exposure to metal debris, e.g. Cobalt-Chromium-Molybdenumalloy metal debris. The pathophysiological reasons for this remain largely unknown. But they are different than the well established long term, mechanisms by which particulate plastic and metal debris cause failure by inducing a subtle but persistent innate macrophage inflammatory responses that invades the bone-implant interface and leads to bone resorption and eventual aseptic loosening of the implant. Sites of inflammation or tissue damage are generally characterized by decreased availability of oxygen, leading to a hypoxic state, which in turn further promotes inflammation and tissue damage at the affected area. Myeloid cells of innate immunity have the capability to respond and function in a hypoxic microenvironment in order to maintain viability, activity and tissue homeostasis. Macrophages are key mediators of inflammatory responses in hypoxic tissues and it has been proposed that a state of hypoxia can act as an “inflammatogen” and activate macrophages that infiltrate hypoxic tissues. Hypoxia inducible factors 1 and 2 are known as primary transcription factors involved in the adaptation of cells to a hypoxic and inflammatory state. HIF-1 is a major transcription factor activated in hypoxia, and is a potent coping mechanism for cells that once activated results in the ability for cells to rapidly respond to changing metabolic demands. HIF-1 is a heterodimeric protein that is formed by two subunits: mortality treatment comparison tatistics HIF-1a and HIF-1b. The subunit HIF-1b is constitutively expressed while HIF-1a is O2 sensitive and is closely associated with myeloid cells inflammatory response and microbicidal activities. In a hypoxic state, 
HIF-1a subunit stabilizes, translocates to the nucleus and dimerizes with HIF-1b beginning the transcription of hypoxia inducible genes, such as vascular endothelial growth factor, a potent angiogenic factor. A hypoxic microenvironment can also contribute to a highly inflamed state by increasing the secretion of pro-inflammatory cytokines. In the context of orthopedics, recent studies have linked VEGF to the development of aseptic loosening.