Dissertation/Thesis Abstract

Mitochondrial Metabolism in Bone Physiology and Pathology
by Shum, Laura C., Ph.D., University of Rochester, 2018, 173; 10792056
Abstract (Summary)

Worldwide, 1 in 3 women and 1 in 5 men over age 50 will experience fractures due to a decline in bone quality. Elucidating the mechanisms for declining bone quality can lead to better therapeutics. A vital, yet overlooked aspect of bone health is the role of mitochondrial metabolism in both bone physiology and pathology. We have found that the ability of stem cells to differentiate into bone forming osteoblasts is sensitive to mitochondrial dysfunction, and therefore preserving mitochondrial function is essential to maintaining bone quality. In human patient samples, we found that osteogenesis following a spinal fusion is correlated with mitochondrial function of bone marrow stem cells. While the decline of bone with aging has been well studied, we were the first to find a concomitant decline in mitochondrial function in bone tissue. The most common mechanism of mitochondrial dysfunction is opening of the mitochondrial permeability transition pore (MPTP), a non-selective proteinaceous pore on the inner mitochondrial membrane, positively regulated by the protein cyclophilin D (CypD). Our CypD knockout mouse model has protected mitochondrial function in bone tissue and no decline in bone quality during aging. While we did show that protecting mitochondrial function is beneficial to age-associated bone loss, our ovariectomy model in the CypD knockout mouse did not show any protection. Thus, age-related and estrogen-related bone loss are likely controlled through different mechanisms. Overall, this work has shown the importance of mitochondrial metabolism in bone health and should be further explored as a new avenue for therapeutic interventions.

Indexing (document details)
Advisor: Eliseev, Roman A.
Commitee: Calvi, Laura M., Hammes, Stephen R., Mooney, Robery A.
School: University of Rochester
Department: Medicine and Dentistry
School Location: United States -- New York
Source: DAI-B 79/10(E), Dissertation Abstracts International
Subjects: Biology, Pathology, Physiology
Keywords: Bone, Metabolism, Mitochondria
Publication Number: 10792056
ISBN: 9780355974867
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