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Date of Award

Summer 2020


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Date Available to Non-EWU Users


Document Type

Thesis: EWU Only

Degree Name

Master of Science (MS) in Biology




Bone remodeling, the process of removing and replacing damaged bone matrix, is a dynamic physiological process essential to maintaining bone composition and integrity. Improper coordination of resorption and formation can lead to pathologic changes in bone composition and quality, as is seen in osteoporosis, a bone disorder most seen in post-metapausal women attributed to decreased estrogen levels. The Notch signal pathway is a highly conserved direct cell communication pathway known to regulate cell proliferation, differentiation and survival in many cell types including the differentiation of osteoclasts from bone marrow macrophages (BMMs). Osteoclastogenesis is initiated in BMMs by receptor activator of nuclear factor kappa-B ligand (RANKL) in the presence of Macrophage Colony Stimulating Factor (M-CSF). This pathway consists of four membrane bound receptors and 5 membrane bound ligands including Jagged1 which is known to play a role in cell-cell communication between a variety of cell types including osteoclasts and osteoblasts. Notch signaling is activated by trans-interactions between the Notch receptor and ligand located on the surface of adjacent plasma membranes. In osteoclasts, the Notch signal pathway has been shown to be inhibitory during early differentiation and critical for maturation and fusion during late differentiation. Cis interactions, receptor-ligand interactions that occur on the same plasma membranes are known to be inhibitory to Notch signaling, the effects of these mechanisms have not been well-studied in osteoclasts. The following is a review of the regulating factors of osteoclastogenesis, current knowledge of the mechanics of Notch signaling and proposal for two lentiviral systems to be implicated in furthering the basis of what is known about the kinetics of the Notch signal pathway during osteoclast differentiation.