The epidermal growth factor receptor plays an anabolic role in bone
The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor present at the cell surface. EGFR binds EGF-like ligands including EGF, amphiregulin, transforming growth factor α (TGF-α), heparin binding EGF (HBEGF), betacellulin (BTC) and epiregulin. Upon activation by its ligands, EGFR is activated by dimerization with phosphorylation on tyrosine residues of its intracellular tail. Then a variety of signaling pathways are recruited by the phosphorylated EGFR to influence cell behavior.
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.
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.
Growth hormone action on bone is partially independent of hepatic IGF-1 production
Growth hormone (GH) plays an important role in regulating bone formation during growth. Although GH can bind its own receptor, it also stimulates the synthesis of insulin-like growth factor I (IGF-I). Hepatic synthesis accounts for most of circulating IGF-1, which acts as a hormone to regulate different processes.
Endocrine Regulation of Male Fertility by the Skeleton
Bone is a dynamic tissue undergoing modeling during childhood and remodeling throughout adulthood. These processes are characterized by the succession of resorption of mineralized bone by osteoclasts and de novo formation by osteoblasts. One of the most powerful hormonal regulations of bone remodeling is exerted by the sex steroid hormones that are necessary to maintain bone integrity. The biological importance of this regulation is best exemplified by the fact that gonadal failure triggers bone loss and causes osteoporosis in postmenopausal women. The study of the interplay between gonads and bone has historically focused on the mechanism whereby sex steroid hormones affect bone mass accrual.
During the past 10 years, bone has emerged as an endocrine tissue. Indeed, an osteoblast-specific secreted molecule, osteocalcin, acts, when uncarboxylated as a hormone favoring β cell proliferation, insulin secretion, and sensitivity. This action is restricted to the uncarboxylated form of osteocalcin that is released in the systemic circulation. Whether or not bone may also regulate gonadal activity has not been explored.
 Download here the slide set presented by Prof. Friedlander, on Thursday, November 10th. |
Latest news
