Master of Science
Goldberg, Harvey A.
Bone sialoprotein (BSP) is an extracellular phosphoprotein that has been associated with mineralizing tissues, such as the periodontium, the fibrocartilaginous enthesis, and long bone formation. In this study, we characterized the phenotype of BSP-deficient rats. Histomorphometric analysis discovered a thinning of the acellular cementum in both 20 and 50 week-old Bsp-/- rats with no related periodontal defects and an organized periodontal ligament. Analysis of the mature quadriceps tendon (QCT) enthesis determined that BSP and osteopontin are present in the calcified fibrocartilage of wild-type rats at 14 weeks. The developing QCT enthesis of Bsp-/- rats appears similar in mineral content, collagen organization, and morphology when compared to wild-type counterparts. Digital measurements of rat tibiae show that bone length does not differ between wild-type and Bsp-/- rats at day of birth. The results of this study suggest that BSP is present in the periodontal and enthesis tissues of the rat, but the rat displays less severe phenotypes than the Bsp-/-mouse.
Summary for Lay Audience
The formation of bone and related mineralized tissues is a complex and highly regulated process. Bone sialoprotein (BSP) is a protein that is expressed at the onset of mineralization in calcified tissues. Much can be learned about a protein by removing its corresponding gene from the genome of animal models and observing the effects. Research on BSP has mainly used the mouse as an animal model for understanding the normal physiological function of the protein, the role of the protein in relevant diseases, and the potential uses of the protein as a therapeutic. However, some experimental studies in the mouse model are limited due to its small size compared to the rat. This study aimed to characterize the effects of the absence of BSP in a novel rat model, and to lay the foundation of future studies on the role and function of BSP. Three regions of the rat were investigated: the dental tissue complex, the development of the tissue at the tendon-bone interface, and the early development of long bones. It was discovered that in the absence of BSP there is a slight defect in the mineralized dental tissues that did not lead to any tooth related defects, such as those observed in the mouse model. Secondly, the junction where the quadriceps femoris tendon inserts into the patella (kneecap) was investigated and although BSP is present in the tendon-bone interface in mature genetically unmodified rats (wild-type), there were no observed differences in the interface structure in the absence of BSP. Furthermore, it was discovered that the mineralization of the tendon-bone interface occurs after four weeks of age. Lastly, the tibia (long bone in lower hind leg) was examined to assess for any delays in its development. Rats lacking the BSP protein did not differ in the length of the tibia at day of birth, and initial analysis suggests that the overall mineral content is not significantly different than wild-type rats. This characterization provides a base of information for future investigations of BSP in the rat model.
Harvey, Benjamin, "The Characterization of the Rat Bone Sialoprotein Knockout Phenotype" (2019). Electronic Thesis and Dissertation Repository. 6649.
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