Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women. Methods A total of 639 postmenopaus...Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women. Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose (70 mg per two weeks) or standard dose (70 mg weekly) of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density (BMD), serum cross-linked C-telopeptide of type I collagen (β-CTX), and total alkaline phosphatase (ALP) were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed. Results rs10925503 polymorphism of GGPPS gene was correlated to serumβ-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype (all P〈0.05). No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly (P〈0.01), and without obvious differences between the low dose and standard dose groups (all P〉0.05). However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels (all P〉0.05). Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.展开更多
The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone tumors.Here,we fabricated polyethylene glycol-conjugated alendronate-functionalized and...The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone tumors.Here,we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine(CQ)-loaded polydopamine nanoparticles(PPA/CQ)for efficient treatment of bone tumors via breaking the vicious cycle.The nanoparticles were efficiently accumulated to the bone tissues,especially the osteolytic lesions around tumors.CQ released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor(TNF)receptor-associated receptor 3 to attenuate the osteolysis in bone tumors.On the other hand,CQ blocked the autophagy in cancer cells,resulting in improved photothermal killing of cancer cells.Finally,the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and osteolysis.This work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors.展开更多
基金Supported by National Natural Science Foundation of China(81570802)National Key Program of Clinical Science(WBYZ2011-873)
文摘Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women. Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose (70 mg per two weeks) or standard dose (70 mg weekly) of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density (BMD), serum cross-linked C-telopeptide of type I collagen (β-CTX), and total alkaline phosphatase (ALP) were measured before and after treatment. GGPPS gene polymorphisms and the changes of BMD and bone turnover markers after treatment were analyzed. Results rs10925503 polymorphism of GGPPS gene was correlated to serumβ-CTX levels at baseline, and patients with TT genotype had significantly higher serum β-CTX level than those with TC or CC genotype (all P〈0.05). No correlation was found between polymorphisms of GGPPS gene and serum total ALP levels, as well as BMD at baseline. After 12 months of treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly (P〈0.01), and without obvious differences between the low dose and standard dose groups (all P〉0.05). However, GGPPS gene polymorphisms were uncorrelated to percentage changes of BMD, serum total ALP, and β-CTX levels (all P〉0.05). Conclusion GGPPS gene polymorphisms are correlated to osteoclasts activity, but all tag single nucleotide polymorphisms of GGPPS gene have no influence on the skeletal response to alendronate treatment.
基金the National Natural Science Foundation of China(21725402,31871010,81971735,81871470 and 81901867)Shanghai Municipal Science and Technology Commission(17XD1401600)+1 种基金the Fok Ying Tong Education Foundation(151036)Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06C322)。
文摘The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone tumors.Here,we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine(CQ)-loaded polydopamine nanoparticles(PPA/CQ)for efficient treatment of bone tumors via breaking the vicious cycle.The nanoparticles were efficiently accumulated to the bone tissues,especially the osteolytic lesions around tumors.CQ released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor(TNF)receptor-associated receptor 3 to attenuate the osteolysis in bone tumors.On the other hand,CQ blocked the autophagy in cancer cells,resulting in improved photothermal killing of cancer cells.Finally,the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and osteolysis.This work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors.