Effect of Triptolide on Expression of Receptor Activator of Nuclear Factor-κB Ligand in Rat Adjuvant Induced Arthritis

The effect of triptolide （TP） on the expression of receptor activator of nuclear factor-κB ligand （RANKL） and osteoprotegerin （OPG） was explored in rat adjuvant induced arthritis （AA）. AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate （MTX） at the onset （day 9） of arthritis. On the peak of arthritis （day 24）, the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood mononuclear cells （PBMC） was detected. TNF-α and IL-1β levels in peripheral blood were determined. Bone erosion scores were also evaluated. The results showed that bone erosion scores in TP and MTX groups were lower than in AA group （.P〈0.01） ; The expression levels of RANKL in the synovium （P〈0.01） and bone （P〈0.05）, and OPG level in synovium （P〈0.05） were lower in TP group than in AA group （P〈0.05）. In TP group, the expression levels of RANKL mRNA and TNF-α, IL-1β in PBMC were lower than in AA group （all P〈0.01）. It was concluded that TP could inhibit rat adjuvant arthritis bone erosion by suppressing the expression of RANKL.

Influence of baicalin on the expression of receptor activator of nuclear factor-κB ligand and osteoprotegerin in human periodontal ligament cells

Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.

Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

Receptor activator of nuclear factorκB ligand/osteoprotegerin axis and vascular calcifications in patients with chronic kidney disease

Vascular calcifications are commonly observed in patients with chronic kidney disease （CKD） and contri-bute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifcations.

Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

Glycine Attenuates Myocardial Fibrosis in Myocardial Infarction in Rats Partly through Modulating Signal Transducer and Activator of Transcription 3/Nuclear Factor-κB/Transforming Growth Factor-β axis

Objective: Inflammation and fibrosis are strongly associated with each other. Glycine is present in various traditional Chinese medicines and exhibits anti-inflammatory activity. However, the effects of glycine on myocardial fibrosis(MF) in rats with myocardial infarction(MI) have not been reported. The purpose of this study is to investigate the effects of glycine therapy on MF and comprehend its underlying mechanisms. Materials and Methods: Left anterior descending artery ligation-induced MI in Sprague Dawley rats was leveraged to assess the therapeutic effects of Glycine. Rats received either normal saline or glycine(0.5 mg/g bodyweight) for 7 days. Results: Glycine upregulated cardiac ejection fraction and fractional shortening to improve cardiac function, as evaluated by echocardiography. Histological and immunohistochemical analyses demonstrated that glycine could decrease inflammatory cell infiltration and alleviate collagen deposition. Western blotting revealed that nuclear factor-κB(NF-κB)-mediated inflammatory signaling was also downregulated by glycine treatment. The expression of signal transducer and activator of transcription 3(STAT3), tumor necrosis factor-α, and transforming growth factor-β(TGF-β) was decreased significantly in the glycine-treated group compared to the model group. Thus, glycine plays a protective role against myocardial ischemia and subsequent MF. Conclusion: The protective effects of glycine were achieved partly through STAT3/NF-κB/TGF-β signaling pathway.

PTHrP促进RANKL诱导巨噬细胞分化为破骨细胞参与中耳胆脂瘤骨破坏

目的:骨质进行性吸收破坏是中耳胆脂瘤最重要的临床特征之一,可导致一系列颅内外并发症,而目前中耳胆脂瘤骨破坏的机制尚未明确。本研究旨在探究甲状旁腺激素相关蛋白(parathyroid hormone-related protein,PTHrP)参与中耳胆脂瘤骨破坏的机制。方法:收集后天性中耳胆脂瘤患者的25例胆脂瘤标本和13例外耳道正常皮肤组织标本。采用免疫组织化学染色方法检测PTHrP、核因子κB受体活化因子配体(receptor activator for nuclear factor-kappa B ligand,RANKL)和骨保护素(osteoprotegerin,OPG)在中耳胆脂瘤和外耳道正常皮肤组织中的表达,抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色法检测中耳胆脂瘤和外耳道正常皮肤组织中是否存在TRAP阳性多核巨噬细胞。选取小鼠单核巨噬细胞RAW264.7细胞进行干预,分为RANKL干预组和PTHrP+RANKL共同干预组,采用TRAP染色法检测2组破骨细胞的生成情况,实时聚合酶链反应(real-time polymerase chain reaction,real-time PCR)检测干预后2组破骨细胞相关基因TRAP、组织蛋白酶K(cathepsin K,CTSK)和活化T细胞核因子1(nuclear factor of activated T cell cytoplasmic 1,NFATc1)的mRNA表达水平,骨吸收陷窝实验检测2组破骨细胞的骨吸收功能。结果:免疫组织化学染色结果显示,PTHrP和RANKL在中耳胆脂瘤组织中的表达均显著增高,OPG表达降低(均P<0.05),且PTHrP的表达与RANKL、RANKL/OPG比值均呈显著正相关,与OPG表达呈显著负相关(分别r=0.385、r=0.417、r=-0.316,均P<0.05)。同时,PTHrP、RANKL的表达水平与中耳胆脂瘤的骨破坏程度均呈显著正相关(分别r=0.413、r=0.505,均P<0.05)。TRAP染色结果显示中耳胆脂瘤上皮周围基质中有大量TRAP阳性细胞,并存在细胞核数量为3个或3个以上的TRAP阳性破骨细胞。RANKL或PTHrP+RANKL联合干预5 d后,与RANKL干预组相比,PTHrP+RANKL联合干预组的破骨细胞数量显著增加(P<0.05),且破骨细胞相关基因TRAP、CTSK和NFATc1的mRNA表达水平均升高(均P<0.05)。骨吸收陷窝扫描电镜结果显示RANKL干预组、PTHrP+RANKL联合干预组的骨片表面均形成骨吸收陷窝;与RANKL干预组相比,PTHrP+RANKL联合干预组的骨片表面骨吸收陷窝数量显著增加(P<0.05),面积也更大。结论:PTHrP可能通过促进RANKL诱导胆脂瘤组织周围基质中的巨噬细胞分化为破骨细胞,参与中耳胆脂瘤骨破坏。

Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes

Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.

基于核因子κB受体活化因子配体信号通路激活破骨细胞治疗骨结核的研究进展

骨结核是一种严重危害人体健康的骨科感染性疾病,其病灶组织破坏的最大特点是骨质的吸收及破坏,其中破骨细胞是骨吸收的主要细胞。破骨细胞是由造血干细胞分化而来的多核细胞,通常是由核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)与核因子κB受体活化因子(receptor activator for nuclear factor-κB,RANK)调控产生。结核分枝杆菌可以通过RANKL信号通路激活破骨细胞生成转录因子,以增强破骨细胞对骨质的吸收。笔者通过综述RANKL信号通路的结构及破骨细胞的研究进展,以及它们在骨结核临床治疗中可能发挥的潜在作用,为该领域的研究提供新的思路。

龈沟液RANKL、音猬因子水平对牙缺失Nobel种植体早期稳定性评估价值

目的探讨龈沟液核因子-κB受体活化因子配体(RANKL)、音猬因子水平对牙缺失Nobel种植体早期稳定性评估价值。方法选取2020年6月至2021年12月邯郸市第一医院牙缺失患者128例作为观察组,均为Nobel种植体修复,选取同期体检健康者64例作为对照组。对比两组及观察组术后即刻、术后3个月龈沟液RANKL、音猬因子水平、种植体稳定系数(ISQ)值,多重线性回归模型分析Nobel种植体早期稳定性影响因素,并分析龈沟液RANKL、音猬因子水平对早期稳定性评估价值。结果观察组术后3个月龈沟液RANKL、音猬因子水平低于术后即刻,差异有统计学意义(P<0.05);观察组术后3个月ISQ值高于术后即刻,差异有统计学意义(P<0.05)。术后即刻龈沟液RANKL、音猬因子水平与术后3个月ISQ值呈负相关(P<0.05)。术后即刻及术后3个月龈沟液RANKL、音猬因子水平对应的线性系数差异有统计学意义(P<0.05);建立多重线性回归模型:术后3个月ISQ值=100.968-4.607×术后咬(牙合)痛-2.886×常食坚果-0.254×术后即刻龈沟液RANKL-0.280×术后即刻龈沟液音猬因子,回归模型具有统计学意义(P<0.05),自变量可解释术后3个月ISQ值74.59%的变异量。结论牙缺失患者进行Nobel种植后龈沟液RANKL、音猬因子呈低表达,术后通过检测二者水平可有效判断种植体早期稳定性。

Er,Cr:YSGG激光治疗对高糖环境下微螺钉周围炎症及对RANK/RANKL信号通路的影响

目的:探讨铒铬铱钪镓石榴石(Er,Cr:YSGG)激光治疗对高糖环境下微螺钉周围炎症治疗的疗效,并分析与RANK/RANKL信号通路的关系。方法:20只正常健康雄性新西兰兔随机分为A组(微螺钉周健康组)、B组(微螺钉周围炎症组)、C组(微螺钉周围炎症激光治疗组),皮下注射2%四氧嘧啶建立糖尿病模型,下颌双侧无牙区植入微螺钉种植体,3个月后,A组进行菌斑控制,B组、C组用丝线拴结于微螺钉种植体颈部基台处引入炎症,C组予以Er,Cr:YSGG激光治疗。记录菌斑指数、探诊深度、牙龈指数和龈沟液量;ELISA检测龈沟液炎性细胞白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平;CBCT检查微螺钉种植体周围炎周围骨吸收状态;Western blot检测牙龈组织中核因子κB(NF-κB)/NF-κB受体性活化因子(RANK)/NF-κB受体活化因子配体(RANKL)通路相关蛋白表达。结果:CBCT检查显示与A组比较,B组微螺钉种植体周围牙槽骨有明显的炎性吸收,微螺钉种植体-骨界面愈合差,骨附着不足;与B组比较,C组一侧牙槽骨有少量新生纤维成骨。与A组比较,B组PI、PD、GI水平较高,龈沟液量较多,龈沟液中IL-1β、TNF-α和IL-6水平较高,牙龈中NF-κBp65、RANK、RANKL蛋白表达水平较高(P<0.05);与B组比较,C组PI、PD、GI水平较低,龈沟液量较少,龈沟液中IL-1β、TNF-α和IL-6水平较低,牙龈中NF-κBp65、RANK、RANKL蛋白表达水平较低(P<0.05)。结论:Er,Cr:YSGG激光治疗糖尿病兔颌骨微螺钉种植体周围炎的疗效显著,且在NF-κB/RANK/RANKL通路表达调控上可能发挥一定作用。

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

围绝经期女性外周血OSTF1、OPG/RANKL对骨质疏松症的预测价值

目的探讨围绝经期女性外周血破骨细胞刺激因子1(OSTF1)、护骨素(OPG)/核因子-κB受体活化因子配基(RANKL)对骨质疏松症的预测价值。方法选择2021年3月至2023年1月河北省妇幼保健中心收治的165例围绝经期骨质疏松症患者为疾病组,并纳入同期120例围绝经期骨密度正常的健康志愿者为对照组。采用Pearson相关分析外周血OSTF1、OPG/RANKL与骨密度的相关性,并收集基线资料,采用单因素分析和多因素Logistic回归分析骨质疏松症发生的影响因素,并使用受试者工作特征(ROC)曲线分析外周血OSTF1、OPG/RANKL对骨质疏松症的预测价值。结果疾病组患者血清OSTF1、RANKL水平明显高于对照组,血清OPG水平、OPG/RANKL明显低于对照组,差异均有统计学意义(P<0.05)。疾病组患者整体骨密度、腰椎骨密度和T值明显低于对照组(P<0.05)。多因素Logistic回归分析结果显示,OSTF1、OPG/RANKL、OPG、整体骨密度、腰椎骨密度、T值和RANKL是骨质疏松症发生的影响因素(P<0.05)。ROC曲线分析结果显示:血清OSTF1预测骨质疏松症发生的曲线下面积(AUC)为0.772(95%CI:0.705~0.843);OPG/RANKL的AUC为0.616(95%CI:0.531~0.699);2项联合的AUC为0.906(95%CI:0.864~0.952)。结论围绝经期女性外周血OSTF1、OPG/RANKL异常表达,OSTF1和OPG/RANKL可应用于骨质疏松症预测,值得临床进一步研究并推广。

核因子κB受体活化因子信号转导机制与破骨细胞的活化

背景:破骨细胞是目前已知的唯一一种骨吸收细胞,其生命活动对骨骼的正常发育和骨骼损伤修复至关重要。在绝大多数骨病中,破骨细胞均显示出异常增殖分化和骨吸收活性增加,而核因子κB受体活化因子信号是调控破骨细胞生命过程的关键信号通路。目的:总结对破骨细胞核因子κB受体活化因子信号下游靶点及DNA转录因子的最新研究进展,为相关疾病的研究和治疗提供依据。方法:文献检索数据库包括中国知网、万方、维普数据库、PubMed、Embase及Web of Science数据库,中文检索词为“破骨细胞,破骨前体细胞,骨质疏松症,骨代谢,发病机制,表观遗传学,信号通路,信号传导,转录因子,组织工程”,英文检索词为“osteoclasts,osteoclast precursor cells,osteoporosis,bone metabolism,pathogenesis,epigenetics,signaling pathway,signal transduction,transcription factors,tissue engineering”,时间设置为2017-2021年,根据纳入和排除标准共筛选52篇文献。结果与结论:核因子κB受体活化因子的特殊结构决定了其信号传导需要与肿瘤坏死因子受体激活因子6结合来募集多种蛋白、活性酶以及细胞因子,形成具有内在酶活性的核因子κB受体活化因子复合物;该复合物通过激活核因子κB、丝裂原活化蛋白激酶等信号通路的传导,最终调控破骨细胞分化、增殖、骨吸收等生命过程。

辐射对RANKL诱导RAW264.7细胞向破骨细胞分化中CBFα1表达水平的影响

为了研究辐射对于破骨细胞中Notch通路的影响,进一步了解辐射诱发骨损伤的机理,本研究采用核因子κB受体活化因子配体(Receptor activator of nuclear Factor-B Ligand,RANKL)诱导RAW264.7细胞系生成的破骨细胞,经2 Gy 137Csγ射线照射后应用实时定量聚合酶链反应(Real-time polymerase chain reaction,Real-time PCR)方法,检测其Notch通路重要靶位启动子C结合因子α1(C Promoter-Binding Factorα1,CBFα1)表达的变化情况。实验结果表明,在2 Gy 137Csγ射线照射后,CBFα1在RANKL作用下生成的破骨细胞中表达明显增高。辐射诱发的Notch通路中CBFα1表达增高,可能是由于辐射增强了Notch通路对破骨细胞分化的促进作用,增加了破骨细胞的数量,增强了其活性,从而导致骨损伤、骨质疏松、甚至骨折的发病率增高。

桥本甲状腺炎合并甲状腺乳头状癌患者中Toll样受体3和核转录因子-κB的表达及相关性分析

目的分析桥本甲状腺炎(Hashimoto thyroiditis,HT)合并甲状腺乳头状癌(PTC)患者Toll样受体3(toll-like receptor 3,TLR3)和核转录因子-κB(nuclear transcription factor-κB,NF-κB)表达及相关性。方法收取邯郸市中心医院2020年3月~2022年3月收治的130例行手术切除的甲状腺标本,其中正常甲状腺组织标本43例,HT标本47例,HT合并PTC标本40例,分析TLR3和NF-κB在正常甲状腺组织、HT组、HT合并PTC组中的表达,分析HT合并PTC组中TLR3和NF-κB表达与临床病理参数关系,Pearson相关性分析TLR3和NF-κB的关系。结果TLR3在正常甲状腺组织、HT组、HT合并PTC组中的阳性表达率分别为0(0/43)、80.85%(38/47)、90.00%(36/40);NF-κB在以上三组中的阳性表达率分别为0(0/43)、68.09%(32/47)、85.00%(34/40)。TLR3和NF-κB在HT组、HT合并PTC组中的阳性表达率均高于正常甲状腺组织(P<0.05),TLR3和NF-κB表达与性别、年龄、HT合并PTC病理学特征、病灶类型、淋巴结转移、甲状腺包膜侵犯差异比较均无统计学意义(P均>0.05)。TLR3和NF-κB呈显著正相关(r=0.589,P<0.05)。结论TLR3和NF-κB在HT合并PTC组织中的阳性率高于正常甲状腺组织,且二者表达呈正相关。

RANKL/RNAK/OPG信号通路影响小鼠膝关节假体无菌性松动的作用机制

目的研究RANKL/RANK/OPG信号通路在小鼠膝关节假体无菌性松动中的作用机制。方法28只小鼠以计算机随机数字表法分成正常组、实验组,最终均分别纳入12只。实验组通过在胫骨近端骨髓腔中注射钴铬颗粒悬液建立小鼠膝关节假体无菌性松动模型,正常组注射等量等渗盐水。采用实时荧光定量PCR(qRT-PCR)法检测界膜组织中RANKL、RNAK、OPG mRNA表达量;免疫组化染色法检测界膜组织中RANKL、RNAK、OPG、抗酒石酸酸性磷酸酶(TRAP)蛋白表达量。结果与正常组比较,实验组建模后6、12周界膜组织RANKL、RNAK mRNA及蛋白表达量,RANKL/OPG升高,OPG mRNA及蛋白表达量降低(P<0.05)。与建模后6周比较,正常组建模后12周界膜组织RANKL、RNAK mRNA及蛋白表达量及RANKL/OPG降低,OPG mRNA及蛋白表达量升高(P<0.05),实验组界膜组织RANKL、RNAK mRNA及蛋白表达量及RANKL/OPG升高,OPG mRNA及蛋白表达量降低(P<0.05)。与正常组比较,实验组建模后6、12周界膜组织TRAP蛋白表达量升高(P<0.05)。与建模后6周比较,正常组建模后12周界膜组织TRAP蛋白表达量降低(P<0.05),实验组界膜组织TRAP蛋白表达量升高(P<0.05)。结论小鼠膝关节假体无菌性松动的界膜组织中RANKL、RNAK表达量及RANKL/OPG升高,OPG表达量降低,RANKL/RNAK/OPG信号通路表达失衡与其发生、发展相关。

抗MCV抗体与RANKL、OPG、TRACP-5b及RA疾病活动度的相关性研究

目的探索类风湿关节炎(rheumatoid arthritis,RA)患者抗突变型瓜氨酸波形蛋白(mutant citrulline vimentin,MCV)抗体与骨代谢标志物及疾病活动度之间的关系。方法收集119例RA患者临床资料和血清,检测抗MCV抗体及RANKL、OPG和TRACP-5b等骨代谢标志物,分析抗MCV抗体与骨代谢标志物之间的相关性,并探索抗MCV抗体与疾病活动是否有关联。结果RA患者抗MCV抗体滴度与RANKL、TRACP-5b水平及RANKL/OPG均无显著相关性(P>0.05),与OPG呈正相关但相关系数低(r=0.183,P<0.05)。②抗MCV抗体与DAS28(r=0.376,P<0.01)、ESR(r=0.440,P<0.01)、RF-IgM(r=0.376,P<0.01)呈正相关。结论抗MCV抗体与血清中骨代谢相关标志物TRACP-5b、RANKL、OPG、RANKL/OPG均无显著相关性,提示抗MCV抗体可能不直接通过影响骨代谢参与RA骨侵蚀进展。抗MCV抗体与疾病活动度呈正相关,提示它对RA病情评估可能有一定的价值。