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
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
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。
