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Master of Science (MS) in Biology
Osteoclasts are giant, multinucleated cells that, alongside osteoblasts, are central to maintaining physiologically healthy bone. The functions of osteoclasts and osteoblasts-degrading and depositing bone matrix, respectively-are paired in healthy bone tissue, thereby yielding no net bone loss or deposition. When these functions become imbalanced, it results in net bone loss or gain, depending on which cell type is being outcompeted. Osteoporosis is one of the most common pathologies stemming from such an imbalance, and predominantly affects postmenopausal women, as the ablation of circulating estrogen-a pro-death signal for osteoclasts-causes a prolongation of osteoclast lifespan and consequent lengthening of their resorptive activity. This results in a net bone loss and fragile bones, which poses a serious health risk to the affected individuals. Novel methods for inhibiting the formation or function of osteoclasts are of clinical significance, as many current therapies are either cost-prohibitive for some, or the therapy can only be supplied for so long before adverse effects from the therapy start taking a toll. In this study we sought to determine the effect that a2,3-linked sialic acid on the surface of osteoclast precursors has on the formation or function of mature osteoclasts. Previous work by our lab lead, Dr. Jason W. Ashley, initially showed that a prevalent osteoclast biomarker, CD68, is heavily glycosylated during osteoclastogenesis, and further work by previous graduate students indicated that removal of a2 ,3-linked sialic acid adversely affected the formation of mature osteoclasts. We were able to verify that there is widespread a2,3-sialylation of osteoclasts during their differentiation, however, we were unable to reproduce-in RAW 264.7 cells-the morphological changes previously seen in primary bone marrow macrophages following cellsurface a2,3-linked sialic acid ablation. Due to inherent variation between replicate experiments arising from the use of RAW 264.7 cells, this phenomenon could not be validated statistically.
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Harding, Christopher S., "The significance of cell-surface α2,3-linked Sialic Acid in Osteoclasts" (2022). EWU Masters Thesis Collection. 778.