- Browse by Author
Browsing by Author "Condon, Keith"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Estrogen depletion alters mineralization regulation mechanisms in an ovariectomized monkey animal model(Elsevier, 2019-03) Paschalis, E. P.; Gamsjaeger, S.; Condon, Keith; Klaushofer, K.; Burr, David; Anatomy and Cell Biology, School of MedicineOvariectomized animal models have been extensively used in osteoporosis research due to the resulting loss of bone mass. The purpose of the present study was to test the hypothesis that estrogen depletion alters mineralization regulation mechanisms in an ovariectomized monkey animal model. To achieve this we used Raman microspectroscopy to analyze humeri from monkeys that were either SHAM-operated or ovariectomized (N = 10 for each group). Measurements were made as a function of tissue age and cortical surface (periosteal, osteonal, endosteal) based on the presence of calcein fluorescent double labels. In the present work we focused on osteoid seams (defined as a surface with evident calcein labels, 1 μm distance away from the mineralizing front, and for which the Raman spectra showed the presence of organic matrix but not mineral), as well as the youngest mineralized tissue between the second fluorescent label and the mineralizing front, 1 μm inwards from the front with the phosphate mineral peak evident in the Raman spectra (TA1). The spectroscopically determined parameters of interest were the relative glycosaminoglycan (GAG) and pyridinoline (Pyd) contents in the osteoid, and the mineral content in TA1. At all three cortical surfaces, significant correlations were evident in the SHAM-operated animals between osteoid GAG (negative) and Pyd content, and mineral content, unlike the OVX animals. These results suggest that in addition to the well-established effects on turnover rates and bone mass, estrogen depletion alters the regulation of mineralization by GAGs and Pyd.Item Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14(Nature, 2018) Sishtla, Kamakshi; Pitt, Natalie; Shadmand, Mehdi; O'Hare, Michael N.; Sulaiman, Rania S.; Sinn, Anthony L.; Condon, Keith; Pollok, Karen E.; Sandusky, George E.; Corson, Timothy W.; Ophthalmology, School of MedicineThe KIF14 locus is gained and overexpressed in various malignancies, with prognostic relevance. Its protein product, a mitotic kinesin, accelerates growth of normal mammary epithelial cells in vitro and retinoblastoma tumours in a mouse model, while KIF14 knockdown blocks growth of brain, liver, ovarian, breast, prostate, and other tumour cells and xenografts. However, the tumour-initiating effects of Kif14 overexpression have not been studied. We aged a cohort of Kif14-overexpressing transgenic mice and wild-type littermates and documented survival, cause of death, and tumour burden. The Kif14 transgene was expressed in all tissues examined, and was associated with increased proliferation marker expression. Neither mouse weights nor overall survival differed between genotypes. However, Kif14 transgenic mice showed a higher incidence of fatal lymphomas (73 vs. 50%, p = 0.03, Fisher’s exact test), primarily follicular and diffuse B-cell lymphomas. Non-tumour findings included a bilateral ballooning degeneration of lens in 12% of Kif14 transgenic mice but no wild-type mice (p = 0.02). Overall, this work reveals a novel association of Kif14 overexpression with lymphoma but suggests that Kif14 does not have as prominent a role in initiating cancer in other cell types as it does in accelerating tumour development in response to other oncogenic insults.