绝经后女性骨密度及骨保护素与颈动脉粥样斑块形成的关系

目的 探讨绝经后女性骨密度及骨保护素与颈动脉粥样斑块形成的关系.方法 测定218例绝经后女性血清骨保护素(OPG)及血脂的浓度,并进行颈动脉彩超检查及腰椎骨矿密度(BMD)检查.根据颈动脉彩超及腰椎骨密度情况,将研究对象分为正常组,单纯颈动脉斑块形成组(CAP组),单纯骨密度下降组(BMD组).结果 3组血清OPG水平...     

RANKL-OPG在口腔中表达的研究进展

破骨细胞生成因子（RANKL）/骨保护素（OPG）系统是影响破骨细胞分化、发育、调节的重要信号通路,也是全身因子和局部因子调节骨代谢的共同通路[1]。在口腔医学领域中,RANKL/OPG系统也起到相当重要的作用,本文就RANKL/OPG系统在口腔中表达的研究进展作一综述。     

正畸保持期龈沟液骨保护素/核因子kappa B受体活化因子配体水平对牙槽骨改建状态的意义

目的:探讨正畸保持期牙周龈沟液中骨保护素(osteoprotegerin,OPG)和核因子kappa B受体活化因子配体水平(receptor activator of nuclear factor kappa B ligand,RANKL)的变化及相应牙周组织OPG和RANKL表达的变化,为预测保持期牙周骨组织状态是否稳定提供依据。方法:选择6周龄雄性Wista大鼠15只,按时间点(T1:基线,T2:加力14 d,T3:停止加力14 d)分为3组,每组5只。在每个时间点先采集龈沟液样本,应用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测OPG和sRANKL(soluble receptor activator of nuclear factor kappaB ligand)浓度,然后处死大鼠,采用免疫组织化学检测牙周组织中OPG和RANKL表达。结果:龈沟液中sRANKL浓度在T2期明显上升(P<0.05),T3期则显著下降(P<0.05),与T1期几乎相当。龈沟液中OPG浓度在3个时间点的变化差异均无统计学意义(P>0.05);龈沟液中sRANKL/OPG的比值和牙周组织RANKL/OPG的比值变化近似,均在T2期明显增大(P<0.05和P<0.01),在T3期显著减小(P<0.05)。结论:在正畸加力至保持期,龈沟液中sRANKL/OPG的比值可以在一定程度上反映牙周组织中骨改建的状态。     

骨保护素与冠状动脉钙化的相关性研究

目的:探讨血清骨保护素(OPG)水平与冠状动脉钙化(Coronary artery calcification,CAC)的相关性。方法:入选50例患者,所有入选患者均冠状动脉16层螺旋CT扫描,根据结果,CAC的患者30例作为实验组,冠脉无钙化者20例作为对照组,在入院24小时内记录各组患者的一般资料(包括性别、年龄、血脂、血糖、血压等),ELISA法检测各组患者血清OPG水平,计算CAC的积分,分析OPG与CAC的相关性。结果:(1)与对照组相比,CAC患者血清OPG均高于对照组,差异有统计学意义(P<0.01);(2)OPG水平与CAC的程度相关,且随着钙化积分的升高而升高,差异有统计学意义(P<0.01);(3)OPG与FPG及LDL水平正相关(P<0.01或P<0.05)。结论:血清OPG浓度与CAC程度密切相关,随着CAC的积分升高而升高,可能参与了CAC的发展,OPG水平与FPG、LDL水平正相关,提示其参与CAC的发展可能与血糖、血脂代谢有关,共同参与了CAC的发展。     

TNFRSF11B gene polymorphisms 1181G > C and 245T > G as well as haplotype CT influence bone mineral density in postmenopausal women

Objectives

Osteoprotegerin (OPG) inhibits osteoclast function by acting as a decoy receptor for receptor activator of nuclear factor-κB ligand (RANKL), thus being an important candidate gene for osteoporosis. Three recent genome-wide association studies also identified the TNFRSF11B gene, coding for OPG, as playing a key role in bone mineral density (BMD) regulation. As variations in the TNFRSF11B gene could alter the susceptibility to osteoporosis, the aim of study was to investigate association of two TNFRSF11B gene polymorphisms with BMD and serum OPG concentration in postmenopausal women.

Study design

478 postmenopausal women were genotyped for the presence of TNFRSF11B gene polymorphisms 245T > G (rs3134069) and 1181G > C (rs2073618). BMDs and serum OPG concentrations were measured.

Results

Two common haplotypes GT and CT occurred in 41.2% and 52.4% of subjects. In osteoporotic postmenopausal women, lumbar spine BMD was associated with polymorphisms 245T > G and 1181G > C, as well as with CT haplotype (p values 0.013, 0.006 and 0.006, respectively). Additionally, femoral neck BMD showed the association with 245T > G (p = 0.047). No other statistically significant associations with BMD were found for the studied SNPs and haplotypes. No association with serum OPG concentration was shown in any of the studied groups.

Conclusions

Our results suggest that, in postmenopausal osteoporosis, polymorphisms 245T > G and 1181G > C, as well as haplotype CT in TNFRSF11B gene influence BMD.     

各期慢性肾脏病患者骨代谢生化指标与骨密度的相关性

目的 观察各期慢性肾脏病（CKD）患者血清骨代谢生化指标与骨密度（BMD）的变化情况及其相关性,探讨这些指标在肾性骨营养不良（ROD）早期诊断中的意义。 方法 78例入选患者共分6组,其中Ccr≥15 ml/min者按CKD临床1~4期分期标准分为4组; Ccr <15 ml/min者按是否行规律血液透析而分为2组。ELISA法测定骨保护素(OPG)。放射免疫法测定血清骨钙素（OC）、降钙素(CT)。化学发光法测定甲状旁腺素(iPTH)。6组患者中共47例行腰椎及股骨不同部位BMD测定。分析各组患者以上指标的差异及其相关性。 结果 （1）血清OPG、iPTH及磷分别从CKD 3、4、5期开始显著上升（P < 0.01）,其中OPG在血液透析后达（5.10±1.34）ng/L,显著高于透析前的（3.35±0.76） ng/L,差异有统计学意义（P < 0.05）。各期CKD患者血清OC、CT、钙及碱性磷酸酶水平差异无统计学意义,而血液透析可使OC显著升高（P < 0.05）。股骨沃德三角BMD在 CKD 4期患者下降至0.77±0.09,显著低于CKD 1期患者的1.15±0.05,差异有统计学意义（P < 0.01）,而血液透析不影响其水平。（2）血清OPG与Ccr、磷、iPTH、OC呈负或正相关（r分别为-0.70、0.51、0.39、0.36,均P < 0.01）。股骨沃德三角BMD与血清iPTH、OC呈负相关（r分别为-0.59、-0.51,均P < 0.01）;与血清磷、OPG亦呈负相关（r分别为-0.45、-0.48,均P < 0.05）。 结论 CKD患者骨代谢生化指标与BMD均随Ccr下降而出现明显异常,这些变化之间存在一定的相关性。血清OPG改变早于iPTH及BMD,在ROD的早期诊断中意义最大。血液透析可使血清OPG、OC水平升高,但不影响BMD水平。     

Effects of coumestrol on expression of bone markers during primary osteoblastic cells differentiation

目的 观察植物雌激素香豆雌酚对成骨细胞增殖分化的作用并探讨其作用机制.方法 从小鼠颅盖骨获得成骨细胞并用0,10-9～10-5 M香豆雌酚孵育48 h,以17β雌二醇为阳性对照,用酶消化法测定碱性磷酸酶及Ⅰ型胶原含量,放免法测定骨钙素含量,RT-PCR法测定OPG及RANKL mRNA表达情况,Western Blot测定OPG蛋白含量.结果 干预48 h,不同浓度香豆雌酚呈剂量依赖性增加碱性磷酸酶及Ⅰ型胶原含量,10-6 M时达到最大效应(P<0.05),但10-5 M效应有所降低,香豆雌酚轻度增加成骨细胞骨钙素含量,各组间无统计学差异.香豆雌酚呈剂量依赖性增加OPG基因及蛋白的表达(P<0.05),轻度降低RANKL基因的表达.结论 香豆雌酚能增加成骨细胞增殖及分化,可能其部分通过OPG/RANKL发挥作用.     

The effect of risedronate treatment on serum cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study

There is much evidence suggesting that the decline in ovarian function after menopause is associated with spontaneous increases in proinflammatory cytokines. Treatment with risedronate is accompanied by significant changes in bone turnover and bone mineral density. The objective of this study was to determine the effects of risedronate treatment on the level of serum cytokines including receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin among postmenopausal women with osteoporosis. The study group consisted of 61 postmenopausal women with osteoporosis. Patients were randomly divided in two groups: In group 1 (n = 41) postmenopausal women received oral risedronate (35 mg/week), calcium (1,000 mg/day), and vitamin D (400 IU/day) for 12 months. In group 2 (control group; n = 20) patients received only oral calcium (1,000 mg/day) and vitamin D (400 IU/day). Bone mineral density (BMD) of lumbar spine (L1–L4) and proximal femur were determined using dual X-ray absorptiometry at baseline and after one year. Venous blood samples were obtained for determination of serum cytokines including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), RANKL, osteoprotegerin, and markers of bone formation and resorption. Levels of serum cytokines were measured before therapy and after three and 6 months. Markers of bone metabolism were studied before therapy and after 6 months. In group 1 (risedronate plus calcium/vitamin D-treated patients), serum levels of RANKL and IL-1β significantly decreased and the level of osteoprotegerin significantly increased after three and 6 months, but no significant difference was found in TNF-α level. In group 2, however, the level of serum cytokines did not change after three and 6 months. In cases of bone turnover, both markers of bone resorption and formation significantly decreased after 6 months in group 1. In conclusion risedronate could improve osteoporosis by increasing osteoprotegerin and reducing RANKL and IL-1β.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

IL-17 induces myocardial fibrosis and enhances RANKL/OPG and MMP/TIMP signaling in isoproterenol-induced heart failure

Objective

This study was designed to investigate whether IL-17 can regulate the expression of the MMP/TIMP system, the OPG/RANK/RANKL system, or type-I and type-III collagen fibers in a rat model of isoproterenol-induced heart failure (HF). We also investigated the effect of IL-17 on myocardial fibrosis in this model.

Methods

HF was induced in Wistar–Kyoto rats by hypodermic injection of isoproterenol (ISO) twice every 24 h. After 2 months, the surviving rats were divided into three groups: monoclonal Anti-IL-17 Ab (100 μg/day), IgG (100 μg/day) or PBS were injected five times every 48 h (i.p.). One day after the last injection, all of the rats were sacrificed. H&E and Masson staining were used to evaluate myocardial fibrosis, and immunohistochemistry was used to measure the levels of MMP-1, TIMP-1, TIMP-4, OPG, RANKL, type-I and type-III collagen fibers. We also treated adult rat cardiac fibroblasts with IL-17 (10 ng/ml), IL-17 (10 ng/ml) + OPG (10 ng/ml), IL-17 (10 ng/ml) + anti-RANKL Ab (100 ng/ml), or PBS for 24 h, realtime RT-PCR was used to measure the expressions of MMP-1.

Results

The expressions of MMP-1, RANKL, and type-I and -III collagen fibers decreased, and the expressions of TIMP-1, TIMP-4, and OPG increased in the Anti-IL-17 group compared to controls. H&E and Masson staining revealed that blockade of IL-17 can improve myocardial fibrosis in HF. IL-17 increased the expression of MMP-1 in cardiac fibroblasts, and OPG and anti-IL-17 Ab could inhibit this function partly. Thus, IL-17 was dependent on the RANKL/OPG system to induce MMP-1 partly.

Conclusion

Our study demonstrates the contribution of IL-17 to myocardial fibrosis in isoproterenol-induced HF. IL-17 can regulate the RANKL/OPG and MMP/TIMP systems in this model. The RANKL/OPG system is one of intermediaries between IL-17 and MMP-1 in cardiac fibroblasts. As a harmful cytokine, anti-IL-17 treatment is a potential therapeutic strategy in HF.