全球范围内有数亿人口患有骨质疏松和类风湿性关节炎等与骨相关的疾病。对骨代谢发生分子机制的理解对于开发、研制治疗这些疾病的新药十分必要。遗传实验显示:核因子-κB受体性活化因子(receptor activator of NF-κB,RANK)、其配体RA...全球范围内有数亿人口患有骨质疏松和类风湿性关节炎等与骨相关的疾病。对骨代谢发生分子机制的理解对于开发、研制治疗这些疾病的新药十分必要。遗传实验显示:核因子-κB受体性活化因子(receptor activator of NF-κB,RANK)、其配体RANKL和诱饵受体OPG是破骨细胞发育和功能活化的关键调节物,这些研究结果是我们理解骨性疾病的一个重要转折点。RANKL-RANK信号传导可以激活破骨细胞发育所需的一系列下游信号途径。再者,在正常生理和疾病过程中,RANKL-RANK和其他配体-受体系统间的分子交叉串扰(cross-talk)精确调节着骨的动态平衡(homeostasis)。设计靶向针对破骨细胞中RANKL-RANK和他们的信号传导途径的药物可以成为革新许多治疗与骨丢失相关疾病(诸如关节炎、牙齿脱落、癌症转移或骨质疏松等)的新方法。展开更多
In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast d...In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast development as the crucial signaling pathway.;However, accumulating evidence also implies that展开更多
目的:考察强直性脊柱炎(ankylosing spondylitis,AS)患者骨代谢生化指标变化,并分析其与RNAKL-RANK-OPG系统表达之间的相关性。方法:研究对象为40名强直性脊柱炎男性患者,40名健康男性为对照组,记录强直性脊柱炎AS患者的病程,体重指数(b...目的:考察强直性脊柱炎(ankylosing spondylitis,AS)患者骨代谢生化指标变化,并分析其与RNAKL-RANK-OPG系统表达之间的相关性。方法:研究对象为40名强直性脊柱炎男性患者,40名健康男性为对照组,记录强直性脊柱炎AS患者的病程,体重指数(body mass index,BMI),甲状旁腺素(parathyroid hormone,PTH),血钙,血磷,碱性磷酸酶(alkaline phosphatase,ALP)等临床指标,采用双能X线吸收法测定AS患者的骨密度(bone mineral density,BMD),利用免疫分析法检测血清中骨吸收指标骨钙素(bone glutamyl protein,BGP),I型强胶原羧基肽(carboxyterminal propeptide of type I procollagen,PICP),骨碱性磷酸酶(bone alkaline phosphatase,BALP),骨吸收指标抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)及sRANKL,OPG的表达。分析骨代谢指标,RANKL-RANK-OPG与各项临床指标的相关性。结果:AS患者PICP,BALP,TRAP及sRANKL、OPG的表达较正常对照组存在明显的差异,具有统计学意义。不同部位的骨密度发生不同程度的骨量减少和骨质疏松,股骨颈、大转子、转子间和股骨颈分别为28%、45%、40%和50%,与骨代谢指标存在一定的相关性,TRAP与大转子的骨密度成负相关(r=-0.369,P=0.019),PICP与大转子的骨密度成正相关(r=0.391,P=0.013),BGP与转子间的骨密度成负相关(r=-0.419,P=0.009),sRANKL/OPG与腰椎密度均呈现负相关(r=-0.134,P=0.011)。骨代谢指标之间以及与临床指标也存在不同程度的相关性,sRANKL与OPG存在正相关(r=0.369,P=0.019)sRANKL/OPG与sRANKL、OPG存在负相关(r=-0.334,P=0.035;r=-0.983,P=0.000)。结论:AS患者骨代谢发生异常,骨吸收增强。RANKL-RANK-OPG系统失衡可能是AS骨量减少和伴随发生骨质疏松的机制之一。展开更多
Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous ...Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous cytokines,but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis,respectively.The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1).RANKL,sclerostin and DKKs-1 are often up-regulated in bone diseases,and they are the target of new monoclonal antibodies.Data sources The authors performed a systematic literature search in PubMed and EMBASE to June 2018,reviewed and selected articles,based on pre-determined selection criteria.Results We re-evaluated the role of RANKL,osteoprotegerin,sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases,such as type 1 diabetes mellitus (T1DM),alkaptonuria (AKU),hemophilia A,osteogenesis imperfecta (OI),21-hydroxylase deficiency (21 OH-D) and Prader-Willi syndrome (PWS).To do so,we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways have been investigated,and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.Conclusions The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases.Furthermore,for some of them,bone damage began in childhood but only manifested with age.The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children,although further studies need to be carried out.展开更多
文摘全球范围内有数亿人口患有骨质疏松和类风湿性关节炎等与骨相关的疾病。对骨代谢发生分子机制的理解对于开发、研制治疗这些疾病的新药十分必要。遗传实验显示:核因子-κB受体性活化因子(receptor activator of NF-κB,RANK)、其配体RANKL和诱饵受体OPG是破骨细胞发育和功能活化的关键调节物,这些研究结果是我们理解骨性疾病的一个重要转折点。RANKL-RANK信号传导可以激活破骨细胞发育所需的一系列下游信号途径。再者,在正常生理和疾病过程中,RANKL-RANK和其他配体-受体系统间的分子交叉串扰(cross-talk)精确调节着骨的动态平衡(homeostasis)。设计靶向针对破骨细胞中RANKL-RANK和他们的信号传导途径的药物可以成为革新许多治疗与骨丢失相关疾病(诸如关节炎、牙齿脱落、癌症转移或骨质疏松等)的新方法。
文摘In the recent two decades, it has been well elucidated that receptor activator of nuclear factor-κB ligand （RANKL; also known as TNFSF11） binding to its receptor RANK （also known as TNFRSF11A） drives osteoclast development as the crucial signaling pathway.;However, accumulating evidence also implies that
文摘目的:考察强直性脊柱炎(ankylosing spondylitis,AS)患者骨代谢生化指标变化,并分析其与RNAKL-RANK-OPG系统表达之间的相关性。方法:研究对象为40名强直性脊柱炎男性患者,40名健康男性为对照组,记录强直性脊柱炎AS患者的病程,体重指数(body mass index,BMI),甲状旁腺素(parathyroid hormone,PTH),血钙,血磷,碱性磷酸酶(alkaline phosphatase,ALP)等临床指标,采用双能X线吸收法测定AS患者的骨密度(bone mineral density,BMD),利用免疫分析法检测血清中骨吸收指标骨钙素(bone glutamyl protein,BGP),I型强胶原羧基肽(carboxyterminal propeptide of type I procollagen,PICP),骨碱性磷酸酶(bone alkaline phosphatase,BALP),骨吸收指标抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)及sRANKL,OPG的表达。分析骨代谢指标,RANKL-RANK-OPG与各项临床指标的相关性。结果:AS患者PICP,BALP,TRAP及sRANKL、OPG的表达较正常对照组存在明显的差异,具有统计学意义。不同部位的骨密度发生不同程度的骨量减少和骨质疏松,股骨颈、大转子、转子间和股骨颈分别为28%、45%、40%和50%,与骨代谢指标存在一定的相关性,TRAP与大转子的骨密度成负相关(r=-0.369,P=0.019),PICP与大转子的骨密度成正相关(r=0.391,P=0.013),BGP与转子间的骨密度成负相关(r=-0.419,P=0.009),sRANKL/OPG与腰椎密度均呈现负相关(r=-0.134,P=0.011)。骨代谢指标之间以及与临床指标也存在不同程度的相关性,sRANKL与OPG存在正相关(r=0.369,P=0.019)sRANKL/OPG与sRANKL、OPG存在负相关(r=-0.334,P=0.035;r=-0.983,P=0.000)。结论:AS患者骨代谢发生异常,骨吸收增强。RANKL-RANK-OPG系统失衡可能是AS骨量减少和伴随发生骨质疏松的机制之一。
文摘Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous cytokines,but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis,respectively.The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1).RANKL,sclerostin and DKKs-1 are often up-regulated in bone diseases,and they are the target of new monoclonal antibodies.Data sources The authors performed a systematic literature search in PubMed and EMBASE to June 2018,reviewed and selected articles,based on pre-determined selection criteria.Results We re-evaluated the role of RANKL,osteoprotegerin,sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases,such as type 1 diabetes mellitus (T1DM),alkaptonuria (AKU),hemophilia A,osteogenesis imperfecta (OI),21-hydroxylase deficiency (21 OH-D) and Prader-Willi syndrome (PWS).To do so,we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways have been investigated,and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.Conclusions The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases.Furthermore,for some of them,bone damage began in childhood but only manifested with age.The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children,although further studies need to be carried out.
