Bone Abstracts

The fibroblast growth factor receptor 3 (FGFR3) activation leads to dwarfism with a spectrum of severity, hypochondroplasia (HCH), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). Interestingly, FGFR3 mutations localized at the same position in the tyrosine kinase domain are responsible for HCH (p. Lys650Asn), SADDAN (p. Lys650Met) and TD (p. Lys650Glu).The mechanisms of FGFR3 activation ...

Mutations in the C-propeptide cleavage site of both COL1A1 and COL1A2 cause dominant high bone mass (HBM) osteogenesis imperfecta (OI), characterized by bone hypermineralization. To elucidate the role of C-propeptide processing in bone formation, we generated heterozygous HBM mice in which both residues of the COL1A1 cleavage site were mutated to prevent cleavage by BMP1. HBM mice are smaller than WT in both weight and length and have extremely brittle bones....

Angiogenesis and osteogenesis are tightly linked and dependent on each other. Lipocalin 2 (LCN2) is a mechanoresponding adipokine, strongly upregulated in osteogenic cells subjected to microgravity (0.08–0.008 g), in which it impairs osteogenesis and upregulates the osteoclastogenic cytokine, RANKL. We investigated the role of LCN2 in the crosstalk between angiogenesis and osteogenesis in simulated microgravity conditions as a model of mechanical unloading. Mouse and huma...

Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects by translocating to the nucleus and there affects gene transcription, but some effects can also be mediated via extra-nuclear actions of the receptor by, e.g., triggering cytoplasmic signaling cascades. ERα contains various domains and the role of activation functio...

Using a CyPB-null mouse model, we previously demonstrated delayed folding, abnormal post-translational modification and altered crosslinking of type I collagen synthesized by osteoblasts. However, intracellular folding of collagen molecules was further delayed by CsA treatment of CyPB-null cells, suggesting involvement of additional PPIases in collagen folding. Since studies of CyPA functions in osteoblasts have not been reported, we investigated the role of this cytoplasmic P...

Ageing is universally linked to skeletal deterioration. Common mechanisms may control both processes, where dysregulation may predispose to bone loss and osteoarthritis (OA). The epigenetic modifier SirT1 controls lifespan and decreases with age. However, the role of SirT1 in joint disease is unclear. Human tissue samples, novel genetically modified mice, a surgical disease model and advanced cellular and molecular studies were employed to explore the hypothesis that SirT1 is ...