Bone Abstracts

see PP167....

The G protein-coupled receptor, protease-activated receptor 2 (PAR2), is expressed by osteoblasts and required for normal skeletal growth and repair. Prostate cancer (PCa) cells commonly secrete proteolytic activators of PAR2 (including matriptase and kallikrein-related peptidase 4) and frequently form osteogenic metastases in bone. This study was undertaken to investigate the hypothesis that PAR2 activators released by PCa cells modulate osteo...

In a recent unbiased transcriptomic study of genes associated with equine osteochondrosis, we identified several novel cartilage genes. The current study was undertaken to determine whether these genes are regulated during chondrocyte hypertrophy, and to identify novel hypertrophy-associated genes for further study in vitro. Gene expression was investigated by quantitative PCR (qPCR) in different zones of growth cartilage microdissected from equine foetal metatarsal b...

Formation and growth of long bones occur through the process of endochondral ossification, which depends on proliferation and hypertrophy of chondrocytes in growth cartilage. In a subtractive hybridization study of equine cartilage, we recently identified a number of genes, the roles of which in growth cartilage have not been characterized. A subset of these genes was found to be differentially expressed between the zones of equine growth cartilage. The genes encoding ATPase H...

Duchenne muscular dystrophy (DMD) is associated with osteoporosis, and dystrophic (dystrophin-deficient) mdx mice show reduced bone mass characterised by decreased mineral apposition and elevated bone resorption. To investigate a potential role of the G-protein-coupled receptor protease-activated receptor-2 (PAR2) in the muscle and bone pathology associated with DMD, we established a colony of PAR2-null-mdx mice. Limb and diaphragm muscles, tibiae and ser...

We have shown that genetic ablation of Cdh2 (N−cadherin gene) in osteolineage cells results in osteopenia and decreased osteoprogenitor number. Paradoxically, others have shown that mice overexpressing Cdh2 in osteoblasts are also osteopenic; an action linked to a negative effect of N−cadherin (Ncad) on Wnt signaling, via sequestration of low density lipoprotein receptor−related protein−...

Senile osteoporosis and age-related osteopenia are associated with decreased osteoblastogenesis and increased bone marrow adipogenesis. The mechanisms controlling the fate determination of osteoblast to adipocyte differentiation of bone marrow stromal cells (BMSC) during aging are not known. We and others previously showed that the cell-cell adhesion molecule N-cadherin (N-Cadh) expressed in osteoblasts controls bone formation, but little is known about its role in BMSC fate d...

The selective cathepsin K inhibitor odanacatib (ODN) is currently in development for the treatment of postmenopausal osteoporosis. Our goal was to evaluate the effects of ODN vs alendronate (ALN) on bone mass and strength of lumbar vertebrae (LV) in orchiectomized (ORX) rabbits, a model of male osteoporosis. Adult male rabbits (11 months old) were subjected to sham- (n=20) or ORX-surgery (n=24/group) for 7.5 months before dosing initiated. ORX animals were ra...

This study examined the anti-osteoclastogenic effect of n-butanol extracts of Panax notoginseng on the receptor activator of NF-kB ligand (RANKL) induced RAW264.7 cells. Panax notoginseng is commonly used to treat chronic liver disease. Notoginseng has many beneficial effects, such as the suppression of liver fibrosis and anti-cancer activities. Notoginseng contains several biologically active components, such as ginsenosides Rb1, Rg1...

Type 2 diabetes mellitus impairs bone quality and increases fracture risk. We showed that diabetic ZDF rats have low bone mass due to impaired osteoblastogenesis, which can be partially reversed with an intermittent parathyroid hormone 1–84 (PTH) therapy. It remains unclear, why PTH treatment does not fully restore osteoblast (OB) function in diabetic conditions. Here, we tested if high glucose (HG) conditions lead to a partial PTH resistance in osteoblasts. Pre-osteoblas...