Osteoprotegerin in diabetic osteopathy

AimThe aim of this study is to evaluate the relationship between OPG and the degree of glycaemic control in a population of elderly subjects.Methods and resultsData presented included 172 elderly subjects, of whom 107 were hospitalized for a hip fracture and 65 were non fractured outpatients. All participants received a multidimensional geriatric evaluation and underwent blood sampling. HbA1c, OPG, CTX and OC were measured and DXA scans were performed. Carotid intima-media thickness (IMT) was measured in all outpatients. Diabetic patients had more comorbidities, higher mean values of lumbar spine and femoral neck BMD and T-score, lower circulating levels of OC and CTX, and higher circulating levels of OPG compared to non-diabetic subjects. OPG was directly correlated with HbA1c. This association was most evident in non-fractured elderly subjects. Moreover, diabetic patients with IMT>1.5 mm had greater mean values of OPG than non-diabetic subjects with high IMT and than elderly subjects with IMT < 1.5 mm, with and without T2DM.ConclusionsDiabetic patients have reduced circulating levels of OC and CTX, and elevated serum levels of OPG, suggesting a state of low bone turnover. Reduced bone turnover causes an increase of BMD and could lead to a poor bone quality. OPG and HbA1c were directly correlated and OPG mean values were higher in diabetic patients with poor glucose control. Diabetic osteopathy could be considered a late complication of T2DM, directly related with the degree of glucose control and the duration of the disease.     

血清骨特异性碱性磷酸酶、同型半胱氨酸、护骨素变化对多发性骨髓瘤患者的临床应用价值

目的探讨血清骨特异性碱性磷酸酶(BALP)、同型半胱氨酸(Hcy)、护骨素(OPG)水平变化对多发性骨髓瘤患者的临床应用价值。方法选取2015年1月至2018年12月我科就诊的多发性骨髓瘤患者106例(实验组),健康对照组58例(对照组),比较两组受试者血清BALP、Hcy、OPG水平差异,观察血清BALP、Hcy、OPG在不同分期多发性骨髓瘤患者中的变化;Pearson分析血清BALP、Hcy、OPG变化与多发性骨髓瘤的相关性,ROC曲线分析血清BALP、Hcy、OPG对多发性骨髓瘤患者预后的预测价值。结果实验组血清Hcy水平高于对照组(P<0.05),实验组血清BALP、OPG水平低于对照组(P<0.05)。实验组治疗后不同预后患者的血清BALP、Hcy、OPG水平相比,差异具有统计学意义(P<0.05)。多发性骨髓瘤患者血清Hcy水平分别与血清β2-MG、LDH水平呈正相关(P<0.05),血清BALP、OPG水平与血清β2-MG、LDH水平呈负相关(P<0.05)。ROC曲线结果示:血清BALP、Hcy、OPG联合检测的曲线下面积为0.889,灵敏度和特异性分别为0.892和0.857。结论血清BALP、Hcy、OPG变化对多发性骨髓瘤病情发生发展具有重要意义;血清BALP、Hcy、OPG对多发性骨髓瘤患者的预后具有预测价值。     

Molecular mechanisms for bone resorption by gingipains: Degradation of osteoprotegerin by lysine-specific gingipain is a key factor for enhanced osteoclastogenesis

BackgroundPeriodontitis is a chronic inflammatory disease accompanied by alveolar bone loss. Porphyromonas gingivalis, which plays a key role in the etiology of periodontitis, produces cysteine proteases called gingipains to promote proteolysis. Gingipains are classified into two groups based on their cleavage site specificity, specifically arginine-specific gingipains (Rgps) and lysine-specific gingipains (Kgps).HighlightWe found that osteoclast differentiation induced by active vitamin D₃, Toll-like receptor ligands including lipopolysaccharide, and inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β was enhanced by a secreted Kgp in co-cultures of mouse osteoblasts and bone marrow cells, whereas RgpB had no effect on osteoclast differentiation under the same experimental conditions. The effect of Kgp on osteoclast differentiation was completely blocked by an inhibitor of Kgp. Further, osteoprotegerin (OPG), a protein that regulates osteoclast differentiation, was degraded by Kgp. Kgp-mediated osteoclast differentiation was not observed in co-cultures of OPG-deficient osteoblasts and bone marrow cells.ConclusionOur data suggests that degradation of OPG by Kgp is a crucial event in the progression of osteolysis in periodontitis.     

Elevated serum receptor activator of NFκB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP)3, and ProMMP1 in patients with juvenile idiopathic arthritis

We studied the serum levels of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), pro-matrix metalloproteinase (MMP) 1, MMP3, and tissue inhibitor of metalloproteinase (TIMP) 1 in patients with juvenile idiopathic arthritis (JIA) and correlated these with different disease variables. Sera of 70 patients with JIA (ILAR 2001 criteria) and 33 age- and sex-matched controls were assayed by enzyme-linked immunosorbent assay. Nonparametric tests were used for analysis of data. The subtype distribution of the JIA patients was: enthesitis-related arthritis (ERA) 24, polyarticular 22, systemic onset 13, oligoarticular 8, and others 3. The median level of RANKL, OPG, pro-MMP1, MMP3, and TIMP-1 were elevated in JIA patients as compared to controls (p < 0.001). There was no difference in levels among different types of JIA. RANKL/OPG ratio was elevated in all subtypes of JIA. MMP3/TIMP-1 ratio correlated with measures of disease activity including swollen and tender joint count, erythrocyte sedimentation rate, and disease activity score (rS 0.28, p < 0.05). Ours is the first study to show elevated RANKL in serum of patients with JIA. Further, our data suggest that patients with ERA have similar levels to other forms of JIA. Association of the MMP3/TIMP-1 ratio with disease activity suggests that it may be a useful biomarker for follow-up.     

骨保护素与代谢综合征

骨保护素(OPG)是一种分泌型糖蛋白,属于肿瘤坏死因子受体超家族成员,不仅在骨代谢过程中起重要作用,而且是重要的血管调节因子,能够保护血管内皮细胞,抑制血管钙化和动脉粥样硬化.代谢综合征(MS)包括腹型肥胖、胰岛素抵抗、血脂异常、高血糖、高血压等.MS各组分均为心血管疾病的危险因素,2型糖尿病患者血OPG水平明显升高,但是OPG与MS其他各组分之间的关系日前还存在争议.     

骨保护素和骨唾液蛋白在风湿钙化二尖瓣的表达及意义

目的观察骨保护素和骨唾液蛋白在风湿性心脏病(风心病)二尖瓣的表达。方法将手术切除的42枚二尖瓣分为风心病组24枚和非风心病组18枚,采用免疫组化染色观察骨保护素和骨唾液蛋白在两组的表达。结果风心病组的骨保护素(P<0.001)和骨唾液蛋白(P<0.001)均较非风心病组表达增高。结论在风心病瓣膜中,骨保护素和骨唾液蛋白均呈现高表达,表明风心病瓣膜钙化并非简单的钙盐沉积,很可能是成骨样骨形成。     

人白介素－1β水平与人牙周膜细胞OPG表达关系

目的：检测不同浓度重组人白介素－1β（recombinant human interleukin－1β,rhIL－1β）对体外培养人牙周膜细胞（human periodontal ligament cells,HPDLCs）表达骨保护因子（osteoprotegerin,OPG）的影响,研究rhIL－1β水平对牙周膜细胞骨向分化的作用。方法：正畸需要而拨除的健康前磨牙牙周膜,体外传代培养HPDLCs;ELISA法和RT－PCR法测定不同浓度rhIL－1β（0、5、10、15μg／L）下HPDLCs的OPG分泌量及mRNA表达。结果：ELISA和RT－PCR法检测结果显示,5、10、15μg／L rhIL－1β作用于HPDLCs均会下调其OPG蛋白分泌和mRNA表达。同一时间点与0μg／L对照组比较,5、10、15μg／L组OPG蛋白分泌和mRNA表达依此下调,差异有统计学意义（P＜0．05）。结论：rhIL－1β水平升高会增强对HPDLCs的OPG表达抑制,对牙槽骨健康产生不利影响。     

骨保护素对去卵巢大鼠中种植体骨整合的影响

目的：探索去卵巢大鼠中骨保护素（osteoprotegerin,OPG）对种植体骨整合的影响。方法大鼠接受双侧卵巢摘除术后12周于胫骨近端植入2颗钛种植钉。将大鼠按每组10只随机分为OPG组与对照组。皮下注射OPG（10 mg/kg）或安慰剂每周3次。8周后收集实验标本进行μCT和组织学以及生物力学分析。结果μCT结果显示,与对照组比较,OPG组中增加了124%的骨体积,167%的骨结合,111%的平均骨小梁数目,92%的平均骨小梁厚度,95%的平均连接密度;降低了64%的平均骨小梁分离度。骨组织形态计量学评价显示OPG组增加160%的骨面积密度和234%骨?种植体接触。生物力学测试提示OPG组种植体的最大推力增加228%。结论全身应用OPG可以改善去卵巢大鼠骨内种植体骨整合和稳定性,其机制可能是通过增加种植体周围的骨量和改善骨小梁微结构。     

连接酶反应技术检测冠心病三个相关基因的单核苷酸多态性

目的 利用聚合酶链反应-连接酶反应（polymorphism chain reaction-ligase detection reaction,PCR-LDR）技术检测瘦素受体基因Lys109Arg （A/G）、Gln223Arg （A/G）,脂联素基因G276T、T45G,护骨素基因T950C、G1181C六个多态性位点的单核苷酸多态性（single nucleotide polymorphism,SNP）.方法 参照待测多态性位点所在DNA序列设计并合成一对引物及3条探针,先通过PCR反应获得含有待检测突变位点的基因片段,再进行LDR,根据测序电泳结果所显示的含荧光标记的LDR产物的片段长度来判断基因型别.结果 采用PCR技术成功扩增出包含瘦素受体基因（110 bp,130 bp）、脂联素基因（400 bp）、护骨素基因（118 bp,163 bp）多态性位点的基因片段.根据LDR产物片段长度不同进行基因分型,纯合子只有一种片段长度,杂合子包含两种纯合子的片段长度,如瘦素受体基因SNP Lys109Arg （A/G）的PCR产物长度为110 bp,LDR产物片段的长度为110 bp时则判断为AA基因型,112 bp则判断为GG基因型,AG基因型则具有110 bp、112 bp两种片段长度.PCR-LDR基因分型结果与DNA测序技术的检测结果一致（Kappa=1,P=0.00）.结论 PCR-LDR技术简单、快速、准确、成本低,适用于大批量SNP检测.     

实验性大鼠根尖周炎骨质破坏与RANKL／OPG关系的研究

[摘要]目的：观察核因子-κB受体活化因子配体（receptoractivatorfornuclearfactor-κB ligand,RANKL）、骨保护素（osteoprote—gerin,OPG）在大鼠根尖周炎发展各阶段表达的变化与根尖周病损发展之间的关系。方法：选取8周龄雄性Wistar大鼠,随机一侧下颌第一磨牙为实验组,对侧下颌第一磨牙作为对照组;术后1、3、7、14、21d处死动物,拍摄颌骨x线片,计算根尖周骨破坏面积;组织切片,免疫组织化学检测根尖周组织中RANKL、OPG的表达。结果：根尖周骨破坏面积自术后3d开始显著增大,21d达到峰值,呈时间依赖关系;RANKL的表达量在3d组明显增高,7d组表达量到达峰值,14d组开始下降;OPG的表达量在1d组即出现有显著性上升,3d组表达趋于平缓,21d组达峰值。RANKL、OPG的变化与根尖周病变发展的变化趋势有着显著相关性。结论：RANKL／OPG系统在根尖周炎炎症性骨质破坏机制中起重要调节作用。