近中阻生牙邻牙龈沟液中RANKL/OPG变化的研究

目的探讨RANKL/OPG在近中阻生牙邻牙龈沟液中的变化。方法选择30名下颌单侧第三磨牙近中阻生的患者,无炎症,分为有近中阻生牙组和对照组,收集下颌双侧第二磨牙龈沟液,检测RANKL/OPG水平的变化,进行统计学分析。结果有近中阻生牙组与对照组RANKL/OPG差异有统计学意义（P〈0.05）。结论近中阻生牙在无炎症状态时影响邻牙的骨代谢,建议预防性拔除。     

RANKL/OPG比值变化在根尖肉芽肿骨质破坏中的意义

目的 检测核因子kappa B受体活化因子配体（RANKL）和骨保护素（OPG）的蛋白表达,探讨RANKL/OPG比值在根尖肉芽肿骨质破坏中的意义.方法 采用免疫组织化学技术检测30例慢性根尖肉芽肿和10例健康牙周膜组织中RANKL和OPG的表达.分析RANKL/OPG比值与炎症浸润、骨质破坏及临床症状之间的关系.结果 与正常对照组相比,根尖肉芽肿病损组织中的RANKL蛋白表达和RANKL/OPG比值显著升高（P＜0.05）.RANKL和OPG的蛋白表达无相关性（P＞0.05）.与小病损相比,RANKL/OPG比值在大病损中显著升高（P＜0.05）.RANKL/OPG比值与病损炎症浸润程度和有无临床症状均无关（P＞0.05）.结论 RANKL/OPG比值与根尖肉芽肿的病损大小密切相关,提示RANKL和OPG在根尖肉芽肿骨质破坏进程中发挥重要作用.     

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system.     

Plasma osteoprotegerin levels increase with the severity of cerebral artery atherosclerosis

Objectives

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. We investigated whether plasma OPG levels were associated with the presence and severity of cerebral atherosclerosis.

Design and methods

We used an enzyme-linked immunosorbent assay to measure the plasma OPG levels of 107 patients with acute cerebral infarction. We compared the plasma OPG levels according to the presence and number of arteries with cerebral atherosclerosis (≥ 50% stenosis).

Results

Of 107 patients, 73 (68.2%) had cerebral atherosclerosis. OPG levels were increased in patients with cerebral atherosclerosis (374.69 ± 206.48 vs 261.17 ± 166.91 pg/mL, p = 0.006). OPG levels showed positive correlation with the number of cerebral arteries with atherosclerosis (Spearman's rho = 0.342, p < 0.001). After adjustment for vascular risk factors, OPG > 229.9 pg/mL was independently associated with the presence [OR 4.61, 95% CI 1.57–13.55, p = 0.005, binary logistic regression] of cerebral atherosclerosis and number [OR 3.20, 95% CI 1.26–8.12, p = 0.014, ordinal logistic regression] of arteries with cerebral atherosclerosis.

Conclusions

Plasma OPG levels were significantly associated with the presence and severity of cerebral atherosclerosis. This finding suggests that plasma OPG might have a role in cerebral atherosclerosis.     

Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis

Bone metastases cause severe skeletal morbidity including fractures and hypercalcemia. Tumor cells in bone induce activation of osteoclasts, which mediate bone resorption and release of growth factors from bone matrix, resulting in a “vicious cycle” of bone breakdown and tumor proliferation. Receptor activator of NF-κB ligand (RANKL) is an essential mediator of osteoclast formation, function, and survival, and is blocked by a soluble decoy receptor, osteoprotegerin (OPG). In human malignancies that metastasize to bone, dysregulation of the RANK/RANKL/OPG pathway can increase the RANKL:OPG ratio, a condition which favors excessive osteolysis. In a mouse model of bone metastasis, RANKL protein levels in MDA-MB-231 (MDA-231) tumor-bearing bones were significantly higher than tumor-free bones. The resulting tumor-induced osteoclastogenesis and osteolysis was dose-dependently inhibited by recombinant OPG-Fc treatment, supporting the essential role for RANKL in this process. Using bioluminescence imaging in a mouse model of metastasis, we monitored the anti-tumor efficacy of RANKL inhibition on MDA-231 human breast cancer cells in a temporal manner. Treatment with OPG-Fc in vivo inhibited growth of MDA-231 tumor cells in bony sites when given both as a preventative (dosed day 0) and as a therapeutic agent for established bone metastases (dosed day 7). One mechanism by which RANKL inhibition reduced tumor burden appears to be indirect through inhibition of the “vicious cycle” and involved an increase in tumor cell apoptosis, as measured by active caspase-3. Here, we demonstrate for the first time that OPG-Fc treatment of mice with established bone metastases resulted in an overall improvement in survival.     

Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets

Although serum osteoprotegerin (OPG) is significantly increased in diabetic subjects, its potential role in beta cell dysfunction has not been investigated. This study aimed to assess the effect of full-length OPG administered in vivo in mice on pancreatic islet structure and function and its interaction with the renin–angiotensin system (RAS).     

低强度脉冲超声对兔下颌骨骨折愈合中OPG/OPGL及COX-2表达的影响

目的通过观察低强度脉冲超声(low intensity pulsed ultrasound,LIPUS)治疗新西兰大白兔下颌骨骨折后骨保护素(osteoprotegerin,OPG)、骨保护素配体(osteoprotegerin ligand,OPGL)、环氧合酶-2(cyclooxygenase-2,COX-2)蛋白及mRNA的动态变化,探讨LIPUS促进骨折愈合的作用机制。结论健康雄性新西兰大白兔84只,随机分为对照组(42只)和实验组(42只),建立下颌骨骨折模型,用LIPUS治疗,分别于术后1、3、14、21、28、56d各取相同例数动物(n=6)处死取样。采用免疫组织化学、RT-PCR技术检测OPG、OPGL、COX-2蛋白及mRNA动态变化。结果 LIPUS治疗兔下颌骨骨折后,OPG、OPGL、COX-2蛋白浓度和mRNA及OPGL/OPG比值在不同时间点均有不同程度上调(P<0.05),但各指标上调幅度最大(P<0.01)的时间点不同,且上调幅度无相关性,只有OPG的上调幅度与OPGL比较差异有统计学意义(P<0.05)。结论 LIPUS能促进兔下颌骨骨折部位OPG、OPGL、COX-2的表达,从而促进骨折愈合。     

健骨方对激素性股骨头坏死家兔血清OPG、RANKL的影响

目的研究中药组方健骨方对激素性股骨头坏死家兔血清OPG、RANKL的影响。方法将30只家兔分成4组:正常组(A组)6只、模型组(B组)8只、中药低剂量组(C组)8只、中药高剂量组(D组)8只。试验时间共6周,均予C组健骨方混悬液灌胃(含生药3.6 g/kg/d),D组健骨方混悬液灌胃(含生药7.19 g/kg/d);实验开始3周后予B组、C组、D组肌注甲基泼尼龙琥珀酸钠20 mg/kg/d造模一次。采用ELISA法检测血清OPG和RANKL,剖取右后侧股骨头行病理学检测。结果 B组股骨头坏死面积明显高于A组、C组、D组(p<0.01)。B组血清OPG低于C组、D组(p<0.05);B组OPG/RANKL明显低于C组、D组(p<0.01)。股骨头坏死面积与OPG、OPG/RANKL成负相关(p<0.01)。结论健骨方对激素性股骨头坏死家兔的血清OPG、OPG/RANKL下降有改善作用,有助于抑制破骨,促进成骨。     

骨免疫学对骨质疏松症的调控作用研究进展

骨质疏松症是慢性全身性骨病，主要表现为骨量丢失、骨微结构退化，最终导致骨骼的脆性升高，骨折风险增高。目前中国老龄化人数逐步增加，已经步入老龄社会，骨质疏松及其导致的脆性骨折发病率逐年上升，极大地影响了患者的生命安全和生活质量，已经成为亟待解决的难题。在骨免疫学这一概念出现之前，由于免疫细胞在骨髓中形成，所以皆认为骨骼对免疫系统至关重要。但是免疫系统对骨骼的调控功能尚不是很清楚。2000年，Arron在Nature杂志上提出“骨免疫学”这一概念，并指出骨骼与免疫系统之间存在复杂的相互调控作用。自此之后，骨免疫学逐渐成为代谢性骨关节疾病的研究热点。骨免疫学在骨重建过程中具有重要的调控作用，其主要研究内容是阐明免疫系统、骨骼，两者之间存在密切复杂的互相调控机制。骨质疏松症的发生发展过程中，OPG/RANK/RANKL信号系统、免疫细胞及其产生的细胞因子都具有决定性的作用。骨免疫学为抗骨质疏松新型药物的研发奠定了理论根基。     

破骨细胞骨吸收的分子机制

破骨细胞性骨吸收是在骨的微环境内进行的复杂分子生物学反应过程,涉及到众多蛋白质和调控因子的参与。有关破骨细胞的活化,骨基质的吸收,骨吸收的调控等方面,现有的数据还不够充分。本文综述了金属基质蛋白酶(M atrix m eta lloprote inases,MM P s)在破骨细胞移行和骨基质吸收方面的重要作用,以及破骨细胞分化因子(R eceptor activator of NF-κB-ligand,RANKL)和护骨素(O steoprotegerin,OPG)在骨吸收调控网络中的地位。