Bone Abstracts

Cancer-associated muscle weakness is an important paraneoplastic syndrome for which there is currently no treatment. Human breast cancer bone metastases (MDA-MB-231 cells in immune deficient mice) induce extensive bone destruction, leading to the release of TGF-β from the bone matrix. We have previously shown that bone-derived TGF-β is responsible for muscle weakness in this model. Mechanistically, TGF-β signaling increases the expression of NADPH oxidase 4 (Nox...

Up to half of women treated with an aromatase inhibitor (AI) for breast cancer develop muscle weakness, bone loss, and joint pain. Moreover, an elevated state of osteoclastic bone resorption has been shown to prime the bone microenvironment in ways that accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Four-week female athymic nude mice underwe...

see PP474....

Autosomal dominant osteopetrosis type II (ADO2) is a rare osteosclerotic disease due heterozygous missense mutations of the CLC7 gene encoding the type seven chloride channel. Our two labs independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. Homozygous mice showed lack of tooth eruption and died within 30 days of age with severe osteopetrosis and central nervous system degenera...

Autosomal dominant type II osteopetrosis (ADO2) is a rare osteosclerotic disorder due to heterozygous missense mutations of CLC7 gene encoding the type 7 chloride channel. Our two labs (L’Aquila and Indianapolis) independently generated the first C57 black 6 (B6) mouse model of ADO2 by inserting the pG213R-clc7 mutation. We created pG213R-clc7 KI mice using a gene targeting approach. Homozygous mice showed lack of tooth eruption and died within ...