Bone phenotype of lysyl oxidase isoform knockout mice & in vitro expression of lysyl oxidase proenzyme
Alsofi, Loai A.
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Lysyl oxidases constitute a family of enzymes responsible for the formation of cross links in collagen and elastin. These enzymes have also been linked to pathological fibrosis. The importance of collagen in the structural and mechanical properties of bone led us to investigate the hypothesis that the absence of one or more of these enzymes could lead to a significant bone phenotype. This phenotype could resemble osteoporosis or diabetic bone disease. In addition, we tried to overexpress lysyl oxidase proenzyme in vitro. The ability to produce enough amounts of lysyl oxidase proenzyme and the ability to process it and activate it could facilitate the development of drugs that control its activity in pathological fibrosis. Bones from 12-week old mice (8 males and 8 females) with the compound genotype LOX+/-, LOXLl -/- were analyzed. 5 males of the genotype LOX+/+, LOXLl-/were also analyzed. 16 wild type mice (8 males and 8 females) were used as controls. μCT was used to analyze the trabecular and cortical bone morphology of both left femur and L5 vertebrae (n=5). The femora were subsequently subjected to mechanical testing using the twist failure in torsion. Right femurs (n=5) were used for histology and histromorphometric analysis. Tibia and fibula (n=5) were used for cross-link analysis. Two way factor ANOV A with post-hoc Tukey HSD test was used for statistical analysis. A P value of less than 0.05 was used to declare significance. μCT analysis of the trabecular bone in femur distal ... [TRUNCATED]
Thesis (D.Sc.D.)--Boston University, Goldman School of Dental Medicine, 2008 (Dept. of Periodontology and Oral Biology).Includes bibliographical references: leaves 140-148.
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