Defense Date

2009

Document Type

Thesis

Degree Name

Master of Science

Department

Biochemistry

First Advisor

Mattew Beckman

Abstract

Musculoskeletal diseases, in particular osteoporosis, are increasingly becoming more prevalent in the U.S. due to the ageing population (Figure1). It is estimated that one-sixth of 300 million people in U.S. suffer from bone disorders or loss. About 10 million of those people above age 50 suffer from osteoporosis. Patients that suffer from osteoporosis have high morbidity and mortality rates. For instance, patients have decreased bone mineral density (BMD), a measurement of bone density that reflects the strength of bone as represented by calcium content. A decrease in BMD typically leads to an increased risk of bone fractures. In particular, hip fractures have an associated 20% mortality rate 1 year after injury among senior citizens 1. Patients that suffer from musculoskeletal diseases and from bone injuries, not associated with disease, account for 130 million hospital visit per year. Not to mention, 245 billion dollars of healthcare expenditure 2. Over that last 30 years, there has been much improvement in the field of bone research and its application to medicine. It has changed the quality of life and prolonged the life expectancy of patients suffering from bone disease. However, many details remain unknown about the underlying mechanism that control bone metabolism, formation, and healing. Furthermore, current effective therapies to combat bone disorders have limitations including unwanted side effects and prohibitive costs. For example, treatment with glucocorticoids which is a known inducer of osteoblastogenesis in vitro has been shown to produce an osteoporotic phenotype in vivo. Recognizing the importance of bone health and its affordability to the public makes the advancement of therapeutic targets work worth doing. Work in this field will eventually lead to the prevention, treatment, and cure for bone disease. A potential therapeutic candidate that maybe involved directly or indirectly with bone formation is secreted phosphoprotein-24 (Spp24). The following research aims to establish an importance and role for Spp24 in bone differentiation. A novel antibody that detects Spp24 which we have developed and characterized, has allowed us to feasibly study the protein. Our results demonstrate localization of Spp24 in different tissue, the processing of the protein during osteoblastogenesis, and have allowed us to conceptualize possible functions based on our data.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2009

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