Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear ...Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.展开更多
目的:探讨低强度激光(LILT)对正畸牙齿移动的疗效及龈沟液白细胞介素-1β(IL-1β),核因子κB受体激活剂配体(RANKL)和骨保护素(OPG)水平的影响。方法:纳入正畸治疗患者60例,随机分为试验组和对照组各30例,对照组使用牙齿正畸治疗,实验...目的:探讨低强度激光(LILT)对正畸牙齿移动的疗效及龈沟液白细胞介素-1β(IL-1β),核因子κB受体激活剂配体(RANKL)和骨保护素(OPG)水平的影响。方法:纳入正畸治疗患者60例,随机分为试验组和对照组各30例,对照组使用牙齿正畸治疗,实验组加用LILT治疗。比较治疗后牙齿累积移动距离(CMD)和平均回缩速度(ARS),以及不同时间段疼痛VAS评分和龈沟液IL-1β,RANKL和OPG水平。结果:试验组7、14、21 d,28 d牙齿CMD均大于对照组(P<0.05),7、14和21 d ARS均高于对照组(P<0.05),治疗后4、24 h,7、14、21 d VAS评分均低于对照组(P<0.05),7 d OPG低于对照组,7、14和21 d RANKL高于对照组,21 d和28 d IL-1β高于对照组,7 d RANKL/OPG比率高于对照组(均P<0.05)。结论:LILT可通过影响骨代谢加速正畸牙齿的移动,并缓解治疗过程中的牙齿疼痛与牙周炎症。展开更多
核因子-κB受体活化因子配体(receptor activator of Nuclear factor-kappa B Ligand,RANKL)、核因子-κB受体活化因子(receptor activator of nuclear factor-kappa B,RANK)、骨保护素(osteoprotegerin,OPG)作为肿瘤坏死因子家族的成员...核因子-κB受体活化因子配体(receptor activator of Nuclear factor-kappa B Ligand,RANKL)、核因子-κB受体活化因子(receptor activator of nuclear factor-kappa B,RANK)、骨保护素(osteoprotegerin,OPG)作为肿瘤坏死因子家族的成员,通过RANKL/RANK/OPG信号通路调节破骨细胞发生及成熟,调控骨代谢,其表达水平直接影响骨质代谢与重塑,现被广泛研究。RANKL/RANK/OPG通路在口腔颌面部形成及改建过程中发挥了关键作用,直接或间接反映出口腔骨破坏类疾病的发生与发展状态。该通路的失衡往往伴随RANKL的增加和(或)OPG的减少,RANKL/OPG的比值影响破骨细胞的成熟及功能,但部分疾病中相关因子的表达水平存在争议,且尚无能应用于临床疾病诊疗的阈值。本文就RANKL/RANK/OPG信号通路调节机制及其在牙周炎、种植、牙齿发育、正畸、颌面部骨缺损修复与再生等口腔相关领域的研究现状进行综述,以进一步探讨口腔中骨代谢及骨破坏类疾病的调节机制,并评价相关因子作为生物标志物的诊断和预后潜力,以期指导临床诊疗及探寻可能的免疫调节靶点。展开更多
目的:探讨骨保护素(osteoprotegerin, OPG)基因rs2073618、rs3102735位点多态性及突变与绝经后2型糖尿病(Type 2 diabetes mellitus, T2DM)女性骨代谢的关系,为后续治疗提供依据。方法:1) 选取石河子地区研究对象200例,所有研究对象均...目的:探讨骨保护素(osteoprotegerin, OPG)基因rs2073618、rs3102735位点多态性及突变与绝经后2型糖尿病(Type 2 diabetes mellitus, T2DM)女性骨代谢的关系,为后续治疗提供依据。方法:1) 选取石河子地区研究对象200例,所有研究对象均为绝经后女性,根据骨密度(Bone mineral density, BMD)分为:正常对照组(A组)、单纯骨量异常组(B组),根据不同的糖耐量水平分为:单纯T2DM (C组)、T2DM伴骨量异常组(D组)。2) 测定骨、糖、脂、糖化血红蛋白(Glycated hemoglobin, HbA1c)、BMD (L1-4) 及BMD (股骨颈)等相关指标。3) 运用Mass ARRAY质谱仪检测OPG基因位点多态性。4) 多组间计量资料采用方差分析;BMD影响因素采用多元线性回归分析。结果:1) 与A组相比,C组、D组的空腹血糖(FPG)及HbAlc水平升高;D组、B组BMD (L1-4)及BMD (股骨颈)水平降低,(P Objective: To investigate the relationship between rs2073618 and rs3102735 polymorphism and mutation of osteoprotegerin (OPG) gene and bone metabolism in postmenopausal women with Type 2 diabetes mellitus (T2DM), so as to provide evidence for follow-up treatment. Methods: 1) A total of 200 subjects were selected from Shihezi area, all of which were postmenopausal women. According to Bone mineral density (BMD), the subjects were divided into normal control group (group A) and simple abnormal bone mass group (group B), and according to different glucose tolerance levels, they were divided into: simple T2DM (group C) and T2DM with abnormal bone mass (group D). 2) Measurement of bone, sugar, lipid, Glycated hemoglobin (HbA1c), BMD (L1-4), and BMD (neck of femur), respectively. 3) The polymorphism of OPG gene locus was detected by Mass ARRAY mass spectrometer. 4) Analysis of variance was used for measurement data among multiple groups;the influencing factors of BMD were analyzed by multiple linear regression. Results: 1) Compared with group A, fasting blood glucose (FPG) and HbAlc levels in groups C and D were increased. BMD (L1-4) and BMD (neck of femur) levels in groups D and B were decreased (P < 0.05). 2) In group D, Ca of rs2073618 mutant (GG/GC) was higher than that of wild type (CC), and Ca of rs3102735 mutant (CC/TC) was lower than that of wild type (TT). In group C, BMD (1-4) of rs2073618 mutant (GG/GC type) was higher than that of wild type (CC type), P < 0.05. 3) Multiple linear regression analysis: the increase of body mass index (BMI) and triglyceride (TG) is the protective factor for the increase of L1-4 (BMD), and the increase of menopause years is the risk factor. Elevated high density lipopro-tein (HDL-C) is a protective factor for increased bone density of femoral neck, and the increase of menopause years is a risk factor. Conclusion: rs2073618 and rs3102735 polymorphisms of OPG gene are not associated with menopausal T2DM women with OP, but the mutations of these two sites are associated with OP in postmenopausal T2DM women in Shihezi.展开更多
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01C604)。
文摘Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.
文摘目的:探讨低强度激光(LILT)对正畸牙齿移动的疗效及龈沟液白细胞介素-1β(IL-1β),核因子κB受体激活剂配体(RANKL)和骨保护素(OPG)水平的影响。方法:纳入正畸治疗患者60例,随机分为试验组和对照组各30例,对照组使用牙齿正畸治疗,实验组加用LILT治疗。比较治疗后牙齿累积移动距离(CMD)和平均回缩速度(ARS),以及不同时间段疼痛VAS评分和龈沟液IL-1β,RANKL和OPG水平。结果:试验组7、14、21 d,28 d牙齿CMD均大于对照组(P<0.05),7、14和21 d ARS均高于对照组(P<0.05),治疗后4、24 h,7、14、21 d VAS评分均低于对照组(P<0.05),7 d OPG低于对照组,7、14和21 d RANKL高于对照组,21 d和28 d IL-1β高于对照组,7 d RANKL/OPG比率高于对照组(均P<0.05)。结论:LILT可通过影响骨代谢加速正畸牙齿的移动,并缓解治疗过程中的牙齿疼痛与牙周炎症。
文摘核因子-κB受体活化因子配体(receptor activator of Nuclear factor-kappa B Ligand,RANKL)、核因子-κB受体活化因子(receptor activator of nuclear factor-kappa B,RANK)、骨保护素(osteoprotegerin,OPG)作为肿瘤坏死因子家族的成员,通过RANKL/RANK/OPG信号通路调节破骨细胞发生及成熟,调控骨代谢,其表达水平直接影响骨质代谢与重塑,现被广泛研究。RANKL/RANK/OPG通路在口腔颌面部形成及改建过程中发挥了关键作用,直接或间接反映出口腔骨破坏类疾病的发生与发展状态。该通路的失衡往往伴随RANKL的增加和(或)OPG的减少,RANKL/OPG的比值影响破骨细胞的成熟及功能,但部分疾病中相关因子的表达水平存在争议,且尚无能应用于临床疾病诊疗的阈值。本文就RANKL/RANK/OPG信号通路调节机制及其在牙周炎、种植、牙齿发育、正畸、颌面部骨缺损修复与再生等口腔相关领域的研究现状进行综述,以进一步探讨口腔中骨代谢及骨破坏类疾病的调节机制,并评价相关因子作为生物标志物的诊断和预后潜力,以期指导临床诊疗及探寻可能的免疫调节靶点。
文摘目的:探讨骨保护素(osteoprotegerin, OPG)基因rs2073618、rs3102735位点多态性及突变与绝经后2型糖尿病(Type 2 diabetes mellitus, T2DM)女性骨代谢的关系,为后续治疗提供依据。方法:1) 选取石河子地区研究对象200例,所有研究对象均为绝经后女性,根据骨密度(Bone mineral density, BMD)分为:正常对照组(A组)、单纯骨量异常组(B组),根据不同的糖耐量水平分为:单纯T2DM (C组)、T2DM伴骨量异常组(D组)。2) 测定骨、糖、脂、糖化血红蛋白(Glycated hemoglobin, HbA1c)、BMD (L1-4) 及BMD (股骨颈)等相关指标。3) 运用Mass ARRAY质谱仪检测OPG基因位点多态性。4) 多组间计量资料采用方差分析;BMD影响因素采用多元线性回归分析。结果:1) 与A组相比,C组、D组的空腹血糖(FPG)及HbAlc水平升高;D组、B组BMD (L1-4)及BMD (股骨颈)水平降低,(P Objective: To investigate the relationship between rs2073618 and rs3102735 polymorphism and mutation of osteoprotegerin (OPG) gene and bone metabolism in postmenopausal women with Type 2 diabetes mellitus (T2DM), so as to provide evidence for follow-up treatment. Methods: 1) A total of 200 subjects were selected from Shihezi area, all of which were postmenopausal women. According to Bone mineral density (BMD), the subjects were divided into normal control group (group A) and simple abnormal bone mass group (group B), and according to different glucose tolerance levels, they were divided into: simple T2DM (group C) and T2DM with abnormal bone mass (group D). 2) Measurement of bone, sugar, lipid, Glycated hemoglobin (HbA1c), BMD (L1-4), and BMD (neck of femur), respectively. 3) The polymorphism of OPG gene locus was detected by Mass ARRAY mass spectrometer. 4) Analysis of variance was used for measurement data among multiple groups;the influencing factors of BMD were analyzed by multiple linear regression. Results: 1) Compared with group A, fasting blood glucose (FPG) and HbAlc levels in groups C and D were increased. BMD (L1-4) and BMD (neck of femur) levels in groups D and B were decreased (P < 0.05). 2) In group D, Ca of rs2073618 mutant (GG/GC) was higher than that of wild type (CC), and Ca of rs3102735 mutant (CC/TC) was lower than that of wild type (TT). In group C, BMD (1-4) of rs2073618 mutant (GG/GC type) was higher than that of wild type (CC type), P < 0.05. 3) Multiple linear regression analysis: the increase of body mass index (BMI) and triglyceride (TG) is the protective factor for the increase of L1-4 (BMD), and the increase of menopause years is the risk factor. Elevated high density lipopro-tein (HDL-C) is a protective factor for increased bone density of femoral neck, and the increase of menopause years is a risk factor. Conclusion: rs2073618 and rs3102735 polymorphisms of OPG gene are not associated with menopausal T2DM women with OP, but the mutations of these two sites are associated with OP in postmenopausal T2DM women in Shihezi.
