Osteoprotegerin prevents glucocorticoid-induced osteocytes apoptosis in mice
Glucocorticoid excess has negative effects on bone strength, as previously reported in numerous studies. This excess leads to a decreased production of osteoblasts and osteoclasts, associated with a prolongation of osteoclast lifespan. Moreover, glucocorticoid excess leads to massive osteoblast and osteocyte apoptosis associated with an alteration of the lacunar-canalicular network. These combined effects induce an important loss of bone mass and strength. RANKL is well known to promote osteoclast differentiation leading to bone loss. In this study, the authors [1] tested the effect of osteoprotegerin (OPG-Fc), a RANKL decoy receptor, on the decrease of bone strength induced by glucocorticoid excess..
Efficacy of serotonin inhibition in mice models of bone loss
tudying the role played by gut serotonin in bone physiology is an important issue to tackle from a medical perspective.
A recent study showed that decreasing gut-derived serotonin synthesis by utilization of a pharmacological inhibitor of tryptophan hydroxylase 1 (Tph1) could prevent and treat ovariectomy-induced osteoporosis in mice and rats. In this study [1], the authors defined the minimal concentration of this inhibitor (LP533401) to significantly increase bone mass and showed that its anabolic effect persists upon interruption.
Macrophage-CSF is a potent stimulator of osteoclast resorbing activity
Macrophage-CSF (M-CSF) is reported to enhance mature osteoclast survival and motility, but its role in the regulation of bone resorption is unclear. The authors of this study [1] analyzed short-term culture of mature osteoclasts in the presence or in absence of the osteoclast differentiation factor RANK ligand (RANKL) with or without M-CSF treatment.
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Strontium ranelate inhibits key factors affecting bone remodeling in human osteoarthritic subchondral bone osteoblasts
Osteoarthritis (OA) is characterized by the progression of cartilage degeneration associated with remodeling of the subchondral bone. This remodeling is the consequence of an increased bone resorption over bone formation due to abnormal osteoblast phenotype. Bone resorption is mainly due to the differentiation and the activation of osteoclasts by the RANK-RANKL signalling pathway. RANKL is produced by osteoblasts. In osteoarthritis patients, RANKL is thought to be overexpressed, like MMP-2 and MMP-9, two metalloproteases implicated in collagen degradation. This specific degradation favors bone resorption.
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.
 Download here the slide set presented by Prof. Friedlander, on Thursday, November 10th. |
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