Bone Abstracts

Background: Bone fragility and vascular calcifications are to the two main morbidities of the mineral and bone disorders associated with chronic kidney disease (CKD), resulting from a combination of abnormalities such as impaired GH axis, vitamin D deficiency, hyperparathyroidism, increased FGF23 levels, hypogonadism, denutrition and drug toxicity.Methods: In a single-centre ancillary study of the longitudinal prospective European 4C study (Cardiovascula...

Mechanical stimulation triggers periostin (Postn) expression in the periosteum and osteocytes (Oc), which downregulates Sost and activates β-catenin signaling. Hence the cortical bone response to loading is abolished in Postn−/− mice. Here we investigated the role of Oc β-catenin and its interaction with Postn on the bone biomechanical response. Postn−/− were bred with Oc-Ctnn−/− mice to generate Po...

Pparβ is crucial for muscle fatty acid oxidation. Pparβ−/− mice have reduced muscle strength, exercise performance, and also a decreased skeletal response to exercise. Here we investigate the influence of Pparβ on muscle and bone loss with aging, and its role on the bone biomechanical response to loading. Pparβ−/− and Pparβ+/+ mice were monitored at 1, 3 and 18...

Gene deletion or treatments with a cathepsin K (CatK) inhibitor in mature preclinical models result not only result in lower bone resorption but also in higher bone formation (BF) on both remodeling and modeling surfaces. Although increased production of clastokines and matrix-derived growth factors may explain the increased BF at remodeling surfaces, the mechanisms for greater BF at modeling surfaces, including the periosteum, remain unexplained. We hypothesized that the abse...

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...

Periostin is a matricellular protein expressed in late osteoblasts/osteocytes, which levels increase in response to PTH and mechanical loading. In turn periostin contributes to modeling based bone formation while restraining bone remodeling. Periostin is also a substrate of cathepsin K and inhibition of periostin blunts the effects of cathepsin K inhibition on bone. Considering the important role of osteocytes and their cathepsin K expression on osteolysis during lactation, we...

Antiresorptives consistently improve bone mass and structural strength in normally- and under-loaded bones, but concerns have been raised regarding potential effects on skeletal adaptation to fatigue loading, including damage accumulation and atypical fractures. We thus inhibited or activated osteoclasts with OPG-Fc or RANKL treatment, respectively, and evaluated bone damage and strength after fatigue in the early and later phases of repair. Adult male mice were treated with R...

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Bone is a tough composite material, comprised of a compliant collageneous matrix, brittle apatite mineral crystals and a suite of non-collageneous proteins (NCPs). Bone material properties depend on these components, and their interactions at the mineral-collagen interface. ‘Bone mineral density’ (BMD), a parameter used to predict fracture risk, is routinely quantified by DEXA. Previous studies used ex vivo emu tibiae as a model to test the effect of organic...

Sclerostin, a product of osteocytes, is known to inhibit Wnt signaling by binding the LRP5/6 receptor.We investigated the effects of a mutated mouse sclerostin protein (muScl, R118A/R144A) with potential sclerostin antagonistic activity. In vitro, muScl fully competed with wild type sclerostin for binding to LRP6, whereas its IC50 for Wnt3a activity was 4× higher than sclerostin (i.e. 600 nM). Moreover, serum osteocalcin increased in mice a...