Bone Abstracts

Tumour necrosis factor receptor-associated factor 6 (TRAF6) plays a key role in osteoclastogenesis through the regulation of RANK/CD40 TRAF6-mediated signaling. Mice deficient in TRAF6 exhibit high bone mass and were protected against inflammation-induced bone loss. Here we describe the effects of a small-molecule 6877002 that has been shown to prevent the binding of TRAF6 to its domain on RANK/CD40 receptor on osteoclast formation in vitro and in vivo and on...

Purpose: High osteoclastogenesis accompanies early stages of osteoarthritis (OA). Cartilage loss is reduced when osteoclasts are inhibited in mice models with bone hyperresorption. Although several evidences show that osteoclast-produced molecules affects chondrocyte metabolism, the mechanism by which inhibition of osteoclasts protects from cartilage damage is unclear. Our purpose was to investigate the role of Sphingosine 1 Phosphate, a lipid mediator secreted by osteoclasts ...

We previously demonstrated the involvement of Lcn2 in bone loss induced by mechanical unloading. This prompted us to investigate bone phenotype of Lcn2−/− mice by μCT, which showed an osteopenic phenotype, characterized by 40% lower trabecular bone volume, 50 and 21% lesser trabecular number and thickness, respectively, and 20% higher trabecular separation, compared to WT, while cortical thickness was significantly lower (40%) only in elderly Lcn2<s...

Pparγ is a master transcriptional regulator of energy metabolism. We demonstrated that Dmp1-Cre/Lox-mice (KO) have increased bone mass and improved energy metabolism. Here we investigated if Pparγ-deficiency in Dmp1 cells can prevent high fat diet effects on these parameters. For this purpose, WT and KO male mice aged of 16 weeks received a high fat or chow diet (HF 60% vs CD 10% of fat) for 12 weeks. Lean and fat, bone structure, metabolic rate and tissue temperatur...

Type 2 diabetes mellitus prevalence increases with age and the disease predisposes to increased risk of fractures and skeletal complications. One possible contributor to skeletal weakening in diabetes is a decline in blood supply. We hypothesised that bone blood flow is impaired in diabetic mice and that chronic administration of glucagon-like peptide-1 receptor agonists (GLP-1RA) can increase blood flow to bone, thereby stimulating bone formation and improving bone architectu...

Irisin is a hormone-like myokine secreted from skeletal muscle in response to exercise. Considering that an intimate relationship between skeletal muscle and bone has been well established and that physical exercise physiologically stimulates the skeleton strengthening, we explored the involvement of Irisin on bone metabolism.Our findings demonstrated that the myokine Irisin improves cortical bone mass and geometry in vivo, supporting the idea t...