Bone Abstracts

Post-translational modifications of histone N-terminal tail domains affect the local chromatin conformation and serve as a dynamic regulatory layer for controlling gene transcription during cell differentiation. However, the role of epigenetic modifications in the regulation of osteoblast differentiation is still not fully understood. Recently, we identified RCOR2 as a novel regulator of osteoblast differentiation in a genome-wide transcription profiling of mouse MC3T3-E1 cell...

Patients with Duchenne muscular dystrophy (DMD) carry a mutation in the dystrophin gene that leads to progressive muscle degeneration. In addition, DMD patients develop low bone mass especially in long bones and have high incidence of fractures. The underlying mechanisms for decreased bone mass remain unclear but muscle weakness and increased IL6 levels may play a role. Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and strength...

see PP467....

In adults, majority of bone marrow (BM) space of long bones is filled with fat tissue. Adipocytes are also present within trabecular bone areas such as vertebral bodies. Despite its prevalence the roles of BM fat in energy and bone metabolism have been largely overlooked. To characterize bone marrow metabolic activity we measured regional glucose uptake in femoral and vertebral bone marrow during fasting and insulin stimulation in normal weight healthy subjects.<p class="a...

see P162....

Epigenetic mechanisms regulating osteoblast differentiation are still inadequately described. In a genome wide transcriptional profiling of MC3T3-E1 osteoblastic cell line, we identified RCOR2 as a significantly upregulated gene during a differentiation time-course from proliferative to mature osteoblasts. Similar expression profile of RCOR2 was found in mouse calvarial osteoblasts. RCOR2 belongs to CoREST/RCOR family of proteins that regulate action of lysine-specific histone...

Wnt signaling is a major regulator of bone metabolism. We recently reported that mutations in WNT1 gene in humans cause early onset osteoporosis and severe osteogenesis imperfecta. To identify the cellular source and the mechanisms causing these severe phenotypes we generated and analyzed global and conditional Wnt1 knockout mice.Heterozygous Wnt1+/− mice were viable and fertile but Wnt1−/− embryos were lost in ute...

The role of the WNT pathway in skeletal maintenance has been extensively studied since the identification of mutations in key signaling WNT mediators (LRP5 and sclerostin) in high and low bone mass phenotypes. However, the identity of the key WNT ligand that signals via LRP5/6 has remained unknown. We aimed to identify genes with a major effect on the skeleton by studying individuals and families with early-onset osteoporosis or osteogenesis imperfecta (OI).<p class="abste...