Bone Abstracts

To understand differences in bone health between and within populations, it is crucial to characterise bone development during childhood and adolescence. Peak height velocity at age 16 and young adult height at age 23.5 years were recently reported in Gambian males accustomed to low calcium intake1. Our study aims to describe bone accrual after peak height velocity in the same population.We used peripheral quantitative computed tomography to m...

In rural Gambian prepubertal children with low calcium intakes (mean 300 mg/day) we reported positive effects, sustained for at least a year (y), on bone mineral content (BMC) after 12 months supplementation with calcium carbonate to international levels1,2. The group was followed up regularly until the end of height growth, and supplementation did not affect height growth in the girls3. Our aim was to determine whether the supplementation altered the tim...

Delta-like 1/fetal antigen-1 (DLK1/FA1) is a negative regulator of bone mass in vivo as it inhibits osteoblast (OB) and stimulates osteoclast differentiation. However, the molecular mechanisms underlying these effects are not known. Thus, we studied the effect of DLK1/FA1 on different signaling pathways known to regulate OB differentiation. We identified DLK1/FA1 as an inhibitor of BMP2-induced OB differentiation. Stable overexpression of DLK1/FA1 in C2C12 cells or th...

see PP150....

Protein kinases are an important class of regulatory elements and pharmacological targets for treatment of a number of diseases including cancer, heart and lung diseases. However, their role in regulation of the skeletal (mesenchymal) stem cell (MSC) functions and bone formation is not fully understood. Thus, we performed functional screening of human kinome, using three siRNAs for each of the ~700 known kinases represented in the human genome. Activity of alkaline phosphatase...

see P146....

Identifying novel approaches for enhancing osteoblast (OB) differentiation of human skeletal (mesenchymal) stem cells (hMSC) can lead to development of novel anabolic agents required for efficient bone formation. Transforming growth factor-βs (TGF-β1, 2, 3) are one of the most abundant growth factors in bone and play a key role in regulating bone remodeling. Canonical TGF-β signaling inhibits, whereas components of the non-canonical TGF-β signaling (e.g. Ak...

see PP175....

Identifying novel molecules that enhance human skeletal (mesenchymal) stem cells (hMSC) differentiation into osteoblastic bone forming cells (OB), may lead to development of new bone anabolic drugs. We have identified Kix, a small molecule kinase inhibitor that enhanced ex vivo OB differentiation and reduced apoptosis of hMSC. We found that Kix targeted undifferentiated hMSC populations and not their differentiated progeny. In addition, Kix increased in vivo ...

see PP149....