Regulation of RANKL-induced osteoclastogenesis by TGF-β through molecular interaction between Smad3 and Traf6
RANKL plays a central role in osteoclast differentiation. The binding of RANKL to its receptor RANK activates JNK and Map38 signaling pathways, which leads to the differenciation, activation and survival of osteoclasts. Molecular mechanisms underlying the contribution of TGF-β for promoting RANKL induced osteoclastogenesis have not been elucidated. Using a specific inhibitor of TGF-β type 1 receptor kinase activity or introducing a dominant negative type 2 TGF-β receptor, the authors of a recent study [1] almost completely blocked RANKL-induced osteoclastogenesis.
DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss
DLK1 is a transmembrane protein that acts as a membrane-bound or soluble protein to regulate regeneration of a number of adult tissues. Several lines of evidence suggest an important role of DLK1 in skeletal development and function. The aim of this paper [1] was to examine the role of this protein in bone biology using osteoblast specific DLK1 overexpressing mice (Col-Dlk1).
Interferon-γ plays a role in bone formation in vivo and reverses osteoporosis in ovariectomized
Interferon γ (IFN-γ) is a cytokine produced by mesenchymal and immune cells in the bone environment. The aim of this study [1] was to get insights into the role of IFN-γ in bone remodeling.
Using interferon γ receptor R1 knockout mice, the authors were able to show that mice without IFN-γ receptor R1 exhibited a 45% decrease of bone volume associated with significant changes in cortical and trabecular structural parameters. These specific changes are characteristic of the osteoporotic phenotype.
Adipokines and the risk of fracture in older adults
Adiponectin and leptin, two adipokines, have been shown to influence bone metabolism in vitro and in animal models, and they have been associated with bone mineral density (BMD). Little is known about the association between leptin and adiponectin serum levels and the fracture risk. The authors of a recent study [1] tested the hypothesis that low leptin and high adiponectin levels are each individually associated with increased fracture risk in a prospective cohort study, among 3075 elderly men and women.
Use of antidepressant drugs and risk of osteoporotic and nonosteoporotic fractures
The antidepressant classes selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressant drugs (TCAs) have been associated with increased risk of fractures.
 Download here the slide set presented by Prof. Friedlander, on Thursday, November 10th. |
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