Strontium ranelate induces a program gene expression during osteoblast differentiation
Osteoporosis is a progressive and debilitating disease that is characterized by massive bone loss during the first 10 years following the menopause, with a deterioration of bone tissues, and propensity for fragility fractures. Until recently, the major drugs to treat osteoporosis were inhibitors of bone remodeling reducing both bone resorption and formation, or anabolic drugs, increasing bone remodeling by enhancing bone formation, but also increasing bone resorption. Strontrium ranelate is the first antiosteoporotic treatment that has dual mode of action and simultaneously increases bone formation, while decreasing bone resorption, thus rebalancing bone turnover of favor of bone formation.
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Mechanical loading, PPARγ, and osteoblastogenesis
The differentiation of multipotent stemcells of mesodermal origin results in the formation of adipocytes, chondrocytes, osteoblasts, and myoblasts. In humans, osteoporosis and age-related osteopenia are associated with an increase in marrow fat tissue and osteoblast numbers correlated negatively with the number of adipocytes. Osteoblastic differentiation is driven by runx2, and then characterized by the expression of alkaline phosphatase, osteocalcin, and eventually by the mineralization of the extracellular matrix.
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HIFα couples angiogenesis to osteogenesis during skeletal development
Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia inducible factor α (HIFα) pathway. An elegant study [1] provides evidence that HIFα promotes angiogenesis and osteogenesis by elevating vascular endothelial growth factor (VEGF) levels in osteoblasts. Mice overexpressing HIFα in osteoblasts through selective deletion of the von Hippel¿Lindau gene (Vhl), a factor which usually promotes degradation of HIFα , expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones.
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 Download here the slide set presented by Prof. Friedlander, on Thursday, March 29th. |
