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The Role Of Mitofusins In The Osteoclast Lineage, Anna Ballard
The Role Of Mitofusins In The Osteoclast Lineage, Anna Ballard
Arts & Sciences Electronic Theses and Dissertations
Mitochondria exist in a highly dynamic network in many cell types, and mutations in mitochondrial transmembrane GTPase mitofusin2 (MFN2), a key factor that mediates mitochondrial tethering, cause defects in the nervous system. Intriguingly, the skeleton has been overlooked in patients with such mutations. Because expression of MFN2 and its homolog, mitofusin1 (MFN1) increase with maturation of osteoclasts (OCs), which are rich in mitochondria, we sought to determine the role of mitofusins in the OC lineage. Double knockout of Mfn1 and Mfn2 in OC precursors by Lysozyme-M cre reveals that mitofusin activity is required for OC function and maintenance of bone …
The Role Of Tmem178 In Regulation Of Osteo-Immune Activation And Inflammatory Bone Loss, Corinne Elaine Decker
The Role Of Tmem178 In Regulation Of Osteo-Immune Activation And Inflammatory Bone Loss, Corinne Elaine Decker
Arts & Sciences Electronic Theses and Dissertations
Pathological bone loss in human disease such as arthritis is largely due to excessive osteoclast recruitment as a consequence of localized inflammation. Innate immune cells, namely neutrophils and macrophages, infiltrate the joint space and release pro-inflammatory cytokines as well as proteases to drive local tissue damage and inflammation. Importantly, IL-1 and TNF-a in particular act on the synovial fibroblasts as well as directly on osteoclast precursors to potently augment osteoclast differentiation and thus bone resorption. Current therapeutics to treat pathological bone loss are widely unsuccessful at targeting both the resorptive and inflammatory components of disease. We have previously demonstrated that …