【摘 要】
：
Osteoporosis and associated fractures are important cause of mortality and morbidity.Heparanase (HPSE) was shown to be involved in fracture repair in mice.However,its presence and anabolic function in
【机 构】
：
Molecular Pharmacology University of Canberra Head,Trauma and Orhtopaedic Research Unit Laboratory A
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Osteoporosis and associated fractures are important cause of mortality and morbidity.Heparanase (HPSE) was shown to be involved in fracture repair in mice.However,its presence and anabolic function in human bone remodeling remain unclear.We report here HPSE protein expression and localization in human osteoblasts isolated from trabecular bone specimens of patients with rheumatoid arthritis (RA),osteoporosis (OP) and healthy subjects.The expression of HPSE was either not detectable or significantly low in osteoporotic osteoblasts,but was in high levels in RA osteoblasts.We observed that HPSE was co-localized within the nuclei and the gene encoding HPSE was associated with the bone turnover marker,alkaline phosphatase.We further profiled the expression of osteogenic genes in the cells and found that osteogenic genes are downregulated in the osteoporotic osteoblasts,however,striking differences are noted with regard to upregnlated osteogenic genes in RA osteoblasts.When we exposed osteoblasts to exogenous HPSE,we observed that HPSE markedly promoted mineralization in osteoporotic and healthy osteoblasts.Our mechanism studies showed that HPSE appeared to play a role in bone remodeling preceding BMP,VEGF and ALPL s steps during osteoblast cell growth via up-regulating osteogenic gene expression and activating histone H3 phosphorylation.These findings support a novel therapeutic use of heparanase in the prevention and treatment of OP.The findings also reveal exciting new information as to inhibition of HPSE contributes to the treatment of RA.
其他文献
The application of vaccines to cancer is nowadays an attractive possibility thanks to advances in molecular engineering and a better understanding of tumor immunology.Transgenic animal models have pla
Inhibition ofT-cell activation is the most efficient way to prevent transplant rejection.Among the immunosuppressants currently on the market,only calcineurin inhibitors (CNIs) inhibit specifically T-
Human lung cancer is the leading cause of cancer death worldwide.Bevacizumab,a mAb against vascular endothelial growth factor (VEGF),in combination with chemotherapy showed significant therapeutic eff
Description:This symposium is designed to help biotech company scientists understand strategies for dose selection and justification in early development.Methods used to perform pharmacokinetic and ph
Large number of pharmaceutical applications of Chitosan have been studied and reported during last two decades.However few of observations inspired us to study and explore the clinical applications of
Millions of dollars are spent yearly in experiments aimed at reducing the risks inherent in the prediction of toxicity and efficacy of compounds for human medical use.Nonetheless,the predictability of
Testing for the safety of a potential drug has been and maintains to be one major cornerstone and challenge in drug discovery and development.The emerging "new technologies" such as "omics" have incre
Swine share many anatomic and physiologic characteristics with humans which make them one of the primary translational research models.In particular swine display similar physiology to humans for the
With the economic downturn,the R&D budget for drug development had been under a lot of scrunity.Every player is trying to make the most out of their investment.On the other hand,increased awareness on
Many of the worlds problematic pathogens continue to lack effective vaccines against them despite vigorous vaccine development efforts.It appears that many of these "vaccine resistant" pathogens escap