目的:观察补肾活血方通过调节骨保护素(OPG)/核因子κB活化因子受体(RANK)/核因子κB活化因子受体配体(RANKL)系统对慢性肾脏病(CKD)大鼠血管钙化(VC)的抑制作用,探讨补肾活血方抑制CKD大鼠VC的作用机制。方法:60只SD大鼠随机分为正常...目的:观察补肾活血方通过调节骨保护素(OPG)/核因子κB活化因子受体(RANK)/核因子κB活化因子受体配体(RANKL)系统对慢性肾脏病(CKD)大鼠血管钙化(VC)的抑制作用,探讨补肾活血方抑制CKD大鼠VC的作用机制。方法:60只SD大鼠随机分为正常组、模型组及中药组,每组20只,模型组与中药组大鼠实验第1-4周给予250mg·kg-1·d-1腺嘌呤混悬液灌胃及含1.8%高磷饲料喂养4周,第5-8周腺嘌呤改为隔日灌胃,中药组同时按55g·kg-1·d-1剂量补肾活血方灌胃治疗,正常组灌胃等量0.9%氯化钠溶液。给药8周后,HE染色观察肾组织变化,茜素红染色观察主动脉钙化结节情况,检测主动脉钙含量及碱性磷酸酶(ALP)活性,腹主动脉取血检测血清钙(Ca)、磷(P)、血肌酐(Scr)、尿素氮(BUN)、全段甲状旁腺激素(i PTH),Western blot法检测主动脉α-平滑肌蛋白(α-SMA)、ALP蛋白的表达,Real-time PCR法检测主动脉OPG、RANKL m RNA表达。结果:HE染色观察提示:中药组较模型组正常肾小球数目增多,肾小管扩张程度降低,炎性细胞数量下降,腺嘌呤结晶减少。茜素红染色观察提示:与正常组比较,模型组主动脉出现钙化结节,广泛红色颗粒物沉着;与模型组比较,中药组钙化结节减少。与正常组比较,模型组主动脉钙含量及ALP活性升高,血P、Scr、BUN、i PTH水平升高,血Ca水平下降(P<0.01),主动脉ALP蛋白表达明显升高、α-SMA蛋白表达明显下降(P<0.01),模型组主动脉OPG m RNA表达下调、RANKL m RNA表达上调(P<0.01);与模型组比较,中药组主动脉钙含量及ALP活性明显降低(P<0.05),血P、Scr、BUN、i PTH水平均下降(P<0.01,P<0.05),血Ca水平升高(P<0.01),中药组主动脉ALP蛋白表达降低、α-SMA蛋白表达升高(P<0.01),且中药组OPG m RNA表达上调(P<0.01),RANKL m RNA表达有下调趋势,但差异无统计学意义。结论:补肾活血方能够改善CKD大鼠肾脏组织学、肾功能、改善钙磷代谢,上调OPG/RANK/RAN展开更多
Osteoclasts are the bone resorbing cells essential for bone remodeling.Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage.Osteoclastogenesis is composed of several steps including...Osteoclasts are the bone resorbing cells essential for bone remodeling.Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage.Osteoclastogenesis is composed of several steps including progenitor survival,differentiation to mononuclear pre-osteoclasts,fusion to multi-nuclear mature osteoclasts,and activation to bone resorbing osteoclasts.The regulation of osteoclastogenesis has been extensively studied,in which the receptor activator of NF-κB ligand(RANKL)-mediated signaling pathway and downstream transcription factors play essential roles.However,less is known about osteoclast fusion,which is a property of mature osteoclasts and is required for osteoclasts to resorb bone.Several proteins that affect cell fusion have been identified.Among them,dritic cell-specific transmembrane protein(DC-STAMP)is directly associated to osteoclast fusion in vivo.Cytokines and factors influence osteoclast fusion through regula-tion of DC-STAMP.Here we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP.A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone resorption.Cell-cell fusion is essential for a variety of cellular biological processes.In mammals,there is a limited number of cell types that fuse to form multinucleated cells,such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant cells.In most cases,cellcell fusion is beneficial for cells by enhancing function.Myoblast fusion increases myofiber size and diameter and thereby increases contractile strength.Multinucleated osteoclasts have far more bone resorbing activity than their mono-nuclear counterparts.Multinucleated giant cells are much more efficient in the removal of implanted materials and bacteria due to chronic infection than macr展开更多
文摘目的:观察补肾活血方通过调节骨保护素(OPG)/核因子κB活化因子受体(RANK)/核因子κB活化因子受体配体(RANKL)系统对慢性肾脏病(CKD)大鼠血管钙化(VC)的抑制作用,探讨补肾活血方抑制CKD大鼠VC的作用机制。方法:60只SD大鼠随机分为正常组、模型组及中药组,每组20只,模型组与中药组大鼠实验第1-4周给予250mg·kg-1·d-1腺嘌呤混悬液灌胃及含1.8%高磷饲料喂养4周,第5-8周腺嘌呤改为隔日灌胃,中药组同时按55g·kg-1·d-1剂量补肾活血方灌胃治疗,正常组灌胃等量0.9%氯化钠溶液。给药8周后,HE染色观察肾组织变化,茜素红染色观察主动脉钙化结节情况,检测主动脉钙含量及碱性磷酸酶(ALP)活性,腹主动脉取血检测血清钙(Ca)、磷(P)、血肌酐(Scr)、尿素氮(BUN)、全段甲状旁腺激素(i PTH),Western blot法检测主动脉α-平滑肌蛋白(α-SMA)、ALP蛋白的表达,Real-time PCR法检测主动脉OPG、RANKL m RNA表达。结果:HE染色观察提示:中药组较模型组正常肾小球数目增多,肾小管扩张程度降低,炎性细胞数量下降,腺嘌呤结晶减少。茜素红染色观察提示:与正常组比较,模型组主动脉出现钙化结节,广泛红色颗粒物沉着;与模型组比较,中药组钙化结节减少。与正常组比较,模型组主动脉钙含量及ALP活性升高,血P、Scr、BUN、i PTH水平升高,血Ca水平下降(P<0.01),主动脉ALP蛋白表达明显升高、α-SMA蛋白表达明显下降(P<0.01),模型组主动脉OPG m RNA表达下调、RANKL m RNA表达上调(P<0.01);与模型组比较,中药组主动脉钙含量及ALP活性明显降低(P<0.05),血P、Scr、BUN、i PTH水平均下降(P<0.01,P<0.05),血Ca水平升高(P<0.01),中药组主动脉ALP蛋白表达降低、α-SMA蛋白表达升高(P<0.01),且中药组OPG m RNA表达上调(P<0.01),RANKL m RNA表达有下调趋势,但差异无统计学意义。结论:补肾活血方能够改善CKD大鼠肾脏组织学、肾功能、改善钙磷代谢,上调OPG/RANK/RAN
基金Supported by(in part)Grants R01-AR43510 to Boyce BF and R01-AR48697 to Xing L from the National Institute of Arthritis and Musculoskeletal and Skin Diseases,United States
文摘Osteoclasts are the bone resorbing cells essential for bone remodeling.Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage.Osteoclastogenesis is composed of several steps including progenitor survival,differentiation to mononuclear pre-osteoclasts,fusion to multi-nuclear mature osteoclasts,and activation to bone resorbing osteoclasts.The regulation of osteoclastogenesis has been extensively studied,in which the receptor activator of NF-κB ligand(RANKL)-mediated signaling pathway and downstream transcription factors play essential roles.However,less is known about osteoclast fusion,which is a property of mature osteoclasts and is required for osteoclasts to resorb bone.Several proteins that affect cell fusion have been identified.Among them,dritic cell-specific transmembrane protein(DC-STAMP)is directly associated to osteoclast fusion in vivo.Cytokines and factors influence osteoclast fusion through regula-tion of DC-STAMP.Here we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP.A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone resorption.Cell-cell fusion is essential for a variety of cellular biological processes.In mammals,there is a limited number of cell types that fuse to form multinucleated cells,such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant cells.In most cases,cellcell fusion is beneficial for cells by enhancing function.Myoblast fusion increases myofiber size and diameter and thereby increases contractile strength.Multinucleated osteoclasts have far more bone resorbing activity than their mono-nuclear counterparts.Multinucleated giant cells are much more efficient in the removal of implanted materials and bacteria due to chronic infection than macr
