血府逐瘀汤对股骨颈骨折患者TGF-beta、VEGF及BMP-2 表达的影响

目的:探讨血府逐瘀汤对股骨颈骨折术后患者转化生长因子β(TGF-β)、血管内皮生长因子(VEGF)、骨形成蛋白-2(BMP-2)表达的影响。方法:选择2014年2月至2014年8月于我院接受治疗的股骨颈骨折患者80例,随机分为实验组和对照组。对照组行常规治疗方案,实验组在常规治疗基础上加用血府逐瘀汤。观察并比较两组患者治疗前后自觉疼痛程度及骨折处骨组织TGF-β、VEGF及BMP-2表达的变化。结果:治疗后,两组患者harris评分均高于治疗前,实验组显著高于对照组(P0.05)。两组患者的骨折处骨组织TGF-β、VEGF、BMP-2水平均高于治疗前,实验组高于对照组,差异均有统计学意义(P0.05)。结论:血府逐瘀汤能有效提高股骨颈骨折患者骨折处骨组织TGF-β、VEGF、BMP-2的表达,促进股骨颈骨折的恢复,值得临床应用和推广。     

HGF调控β-catenin信号通路对家兔股骨颈骨折修复的影响

摘要 目的：探究HGF调控β-catenin信号通路对家兔股骨颈骨折修复的作用和影响机制。方法：15只股骨颈骨折家兔动物模型随机分为半合成细胞外基质样水凝胶组（sECM组）、sECmM+HGF组和脱钙骨基质组（DBM组）,自体右侧作为实验侧,左侧作为对照侧,对比各组家兔一般情况、骨折愈合质量评分骨痂最大载荷、挠度和刚度、BMSC细胞中BMP-2、TGF-β1、PDGF、bFGF mRNA表达水平和COL-I、Wnt5a、β-catenin和Lef-1蛋白表达水平。结果：术后各周sECM+HGF组和DBM组实验侧骨折愈合质量评分高于对照侧（P<0.05）,且高于同期sECM组实验侧（P<0.05）。术后8周,sECM+HGF组和DBM组实验侧骨痂最大荷载、挠度和刚度均优于对照侧（P<0.05）,且优于sECM组实验侧（P<0.05）。术后2周及4周,sECM+HGF组和DBM组实验侧BMP-2、TGF-β1、PDGF和bFGF表达显著高于对照侧（P<0.05）。且高于同期sECM组实验侧（P<0.05）,术后8周sECM+HGF组和DBM组实验侧BMP-2表达高于sECM组实验侧（P<0.05）。术后2周,sECM+HGF组和DBM组实验侧COL-I表达高于对照侧（P<0.05）。术后2周、4周sECM+HGF组和DBM组实验侧COL-I表达均显著高于同期sECM组实验侧（P<0.05）。术后8周,sECM+HGF组和DBM组实验侧wnt5a表达低于对照侧（P<0.05）且低于sECM组实验侧,β-catenin、Left-1表达显著高于对照侧（P<0.05）,且高于sECM组实验侧（P<0.05）。结论：HGF通过激活Wnt/β-catenin信号通路,上调BMP-2、TGF-β1、PDGF、bFGF和COL-1的表达,显著促进股骨颈骨折家兔的骨折修复过程。     

创伤性骨折血清ALP、OPG表达与Th1/Th2平衡的相关性分析

摘要 目的：探讨创伤性骨折血清碱性磷酸酶（ALP）、骨保护素（OPG）表达与辅助性T细胞1（Th1）/辅助性T细胞2（Th2）平衡的相关性。方法：选取我院2019年2月到2022年12月收治的80例创伤性骨折患者作为研究对象,将其分为观察组,另选取同期来我院体检的80名健康志愿者作为对照组。抽取观察组患者入院后第二天清晨空腹静脉血和对照组清晨空腹静脉血,检测ALP、OPG、Th1、Th2表达水平,并分析血清ALP、OPG表达与Th1/Th2平衡的相关性。术后12个月后对观察组80例患者进行随访,依照患者骨折愈合程度将其分为骨折愈合组（n=54）和延迟愈合组（n=26）,对比两组患者临床一般情况与ALP、OPG、Th1/Th2表达水平,并分析创伤性骨折患者骨折愈合情况影响的多因素。结果：观察组与对照组ALP、OPG表达与辅助性T细胞水平对比差异显著,观察组ALP、OPG、Th2水平明显高于对照组,Th1、Th1/Th2水平明显低于对照组（P＜0.05）;Spearman相关分析结果表明：血清ALP、OPG与Th1/Th2平衡呈负相关（P<0.05）;骨折愈合组和延迟愈合组患者性别、年龄、致伤原因、Th2对比无明显差异（P＞0.05）,两组患者BMI、合并感染ALP、OPG、Th1、Th1/Th2水平对比差异显著（P＜0.05）;对上述单因素分析具有统计学差异指标进行赋值,多因素分析结果表明：ALP、OPG、Th2、Th1/Th2为影响创伤性骨折患者骨折愈合情况的独立影响因素（P＜0.05）。结论：创伤性骨折的发生会导致ALP、OPG水平升高,Th1/Th2平衡改变,患者血清ALP、OPG水平与Th1/Th2平衡关系具有明显相关性。另外,ALP、OPG、Th1、Th1/Th2水平变化可影响创伤性骨折患者术后骨折愈合水平。因此,临床上对于ALP、OPG水平升高,且Th1/Th2失衡患者需警惕骨折愈合不良的发生。     

续骨丹外敷疗法对大鼠胫骨缺损模型血清BMP-2的影响

为观察续骨丹外敷疗法对大鼠胫骨缺损模型血清骨形态发生蛋白-2(BMP-2)表达的影响。给70只SD大鼠右侧胫骨制备1个4 mm缺损,用0.8 mm克氏针内固定。造模1个月后符合标准的大鼠随机分为实验组(药物治疗组)、对照组a(脉冲磁场治疗组)、对照组b(面粉干扰组)和空白组。在干预前、2周、4周后对大鼠右胫骨行X线检查,然后处死动物,收获骨样本,做苏木素-伊红(HE)染色和血清BMP-2检测。干预前,实验组、对照组a、对照组b和空白组,4组大鼠血清BMP-2的含量没有明显差异;干预至第2周时,4组大鼠血清BMP-2的含量与干预前比较均下降,但组间差异均无统计学意义(p0.05);干预4周后,实验组大鼠血清BMP-2的含量高于对照组a、b和空白组,差异均有统计学意义(p0.05),对照组a中BMP-2的含量高于对照组b和空白组,差异均有统计学意义(p0.05),对照组b与空白组比较,差异无统计学意义(p0.05)。4组大鼠血清BMP-2的含量在干预前、2周和4周后的变化趋势是:实验组和对照组a先降后升,对照组b和空白组一直下降。续骨丹外敷疗法和脉冲电磁场疗法在实验干预至第4周时均能上调骨缺损大鼠BMP-2的表达,有利于骨缺损的愈合,但续骨丹外敷疗法对BMP-2的调节作用上明显优于脉冲电磁场。     

强骨胶囊对老年股骨头近段骨折延迟愈合患者血清BMP-2 及IGF-1水平的影响

目的:探究强骨胶囊对老年股骨头近段骨折延迟愈合患者血清骨形态发生蛋白-2(BMP-2)及胰岛素生长因子-1(IGF-1)水平的影响。方法:选择我院收治的股骨近端骨折延迟愈合的老年患者41例,随机分为实验组及对照组。对照组19例予钙片;实验组22例予强骨胶囊。对比两组的临床疗效及治疗前后血清BMP-2及IGF-1水平的改变。结果:实验组总有效率(95.5%)高于对照组(78.9%),差异具备统计学意义(P0.05)。两组血清BMP-2及IGF-1水平均较治疗前显著升高(P0.05),且实验组血清BMP-2和IGF-1水平较对照组高(P0.05)。治疗后,两组血浆粘度均下降、骨密度值(BMD)均升高(P0.05);与对照组相较,实验组血浆粘度降低、BMD较高(P0.05)。结论:强骨胶囊能够有效改善老年股骨头近段骨折延迟愈合,促进骨折断端的愈合,推测其机制与增加患者血清BMP-2及IGF-1水平有关。     

熊果酸对酒精性骨质疏松大鼠骨形成、骨矿化的影响

目的：探讨熊果酸对酒精所致骨质疏松大鼠骨形成、骨矿化的影响。方法：雄性Wistar大鼠60只,按体重随机分为空白对照 组、熊果酸对照组、模型组、熊果酸低、中、高剂量组,同时分别给予生理盐水、150 mg/kg 熊果酸、50%酒精,50 mg/kg 熊果酸,100 mg/kg 熊果酸,150 mg/kg 熊果酸灌胃。熊果酸对照组生理盐水剂量同空白组,熊果酸低、中、高剂量组酒精剂量同模型组。灌胃共 持续8 周。磷钼酸法检测血清磷(P)含量,比色法检测血清钙(Ca)含量,酶联免疫吸附（ELISA）法检测血清骨钙素(BGP)、骨形成蛋 白-2(BMP-2)浓度;HE 染色法观察股骨结构的病理学变化。结果：与空白对照组相比较,模型组血清BGP、BMP-2 和Ca、P 均明显 降低,且有统计学差异(P < 0.05),但熊果酸对照与空白对照组各项指标结果相近。熊果酸中、高剂量组大鼠血清BGP、Ca 和P 水 平均较模型组有显著升高,差异具有统计学意义(P < 0.05),但仅熊果酸高剂量组血清BMP-2 显著升高(P < 0.05)。股骨组织HE 染色结果显示,空白对照组骨小梁致密、规则且较粗,粗细均匀;模型组骨小梁稀松、不规则、粗细不均匀,甚至可见骨小梁断裂; 熊果酸中、高剂量组骨小梁致密、规则、较厚、粗细均匀,未见骨小梁断裂。结论：熊果酸能够促进酒精性骨质疏松大鼠的骨形成, 抑制骨矿物质的流失,在改善酒精致骨质疏松方面有一定的保护作用。     

姜黄素通过激活Wnt/β-catenin信号通路促进骨折愈合

摘要 目的：探讨姜黄素治疗骨折的潜在应用价值及其对Wnt/β-catenin信号通路的可能影响。方法：本研究建立了胫骨骨折SD大鼠模型（模型组）,然后应用不同剂量的姜黄素（50、100和200 mg/kg/d）治疗胫骨骨折大鼠4周。治疗4周后,通过苏木精和伊红（HE）染色评价骨折区域的形态,通过ELISA法测定大鼠血清中TGF-β、BMP-2、OC和CTX-I水平。应用不同浓度的姜黄素（0、5、10、20、和50 μM）或Wnt/β-catenin信号通路抑制剂ICG-001（10 μM）处理成骨细胞3 d,然后检测细胞的ALP活性、PCNA和COL-1的含量及Wnt /β-catenin信号通路相关分子的表达水平。结果：不同剂量的姜黄素处理组大鼠的小梁状骨和胶原明显增多。与模型组相比,不同剂量的姜黄素处理组大鼠血清中的TGF-β、BMP-2和OC水平均升高,而CTX-I水平降低（P<0.05）;与模型组相比,不同剂量的姜黄素处理组大鼠骨折区域中的COL-1阳性率升高（P<0.05）,而COL-2水平未发生显著变化（P>0.05）。在药物干预3 d后,10和20 μM的姜黄素促进了细胞增殖,而100和200 μM的姜黄素抑制了细胞增殖（P<0.05）。与0 μM组比较,10 μM和20 μM的姜黄素组成骨细胞上清液中PCNA和COL-1水平及ALP活性水平均显著升高（P<0.05）。与模型组相比,不同剂量的姜黄素处理组大鼠骨折区域中的Wnt-3a和β-catenin mRNA和蛋白表达水平升高,而GSK-3β降低（P<0.05）。与姜黄素组相比,ICG-001处理后成骨细胞活力、ALP活性和β-catenin的表达水平均显著下降（P<0.05）。结论：姜黄素通过激活Wnt/β-catenin信号通路促进骨折愈合并刺激成骨细胞的增殖和分化。     

熊果酸对酒精性骨质疏松大鼠骨形成、骨矿化的影响（英文）

目的:探讨熊果酸对酒精所致骨质疏松大鼠骨形成、骨矿化的影响。方法:雄性Wistar大鼠60只,按体重随机分为空白对照组、熊果酸对照组、模型组、熊果酸低、中、高剂量组,同时分别给予生理盐水、150 mg/kg熊果酸、50%酒精,50 mg/kg熊果酸,100mg/kg熊果酸,150 mg/kg熊果酸灌胃。熊果酸对照组生理盐水剂量同空白组,熊果酸低、中、高剂量组酒精剂量同模型组。灌胃共持续8周。磷钼酸法检测血清磷(P)含量,比色法检测血清钙(Ca)含量,酶联免疫吸附(ELISA)法检测血清骨钙素(BGP)、骨形成蛋白-2(BMP-2)浓度;HE染色法观察股骨结构的病理学变化。结果:与空白对照组相比较,模型组血清BGP、BMP-2和Ca、P均明显降低,且有统计学差异(P0.05),但熊果酸对照与空白对照组各项指标结果相近。熊果酸中、高剂量组大鼠血清BGP、Ca和P水平均较模型组有显著升高,差异具有统计学意义(P0.05),但仅熊果酸高剂量组血清BMP-2显著升高(P0.05)。股骨组织HE染色结果显示,空白对照组骨小梁致密、规则且较粗,粗细均匀;模型组骨小梁稀松、不规则、粗细不均匀,甚至可见骨小梁断裂;熊果酸中、高剂量组骨小梁致密、规则、较厚、粗细均匀,未见骨小梁断裂。结论:熊果酸能够促进酒精性骨质疏松大鼠的骨形成,抑制骨矿物质的流失,在改善酒精致骨质疏松方面有一定的保护作用。     

Wnt5a对成骨前体细胞分泌和分化功能的影响

目的研究Wnt5a对成骨前体细胞分泌和分化功能的影响,并对其分子机制进行初步探讨。方法 Wnt5a刺激成骨前体细胞(MC3T3-E1)后,用双抗体夹心ELISA法检测细胞上清中骨保护素(Osteoprotegerin,OPG)、IL-6、IL-1β及TNF-α的表达水平;用碱性磷酸酶(Alkaline phosphatase,ALP)检测试剂盒及实时定量PCR法检测ALP的表达量及活性;通过实时定量PCR方法检测Ror2基因表达水平,应用Western blot检测细胞JNK蛋白表达变化。结果 Wnt5a抑制了OPG的表达,增加了IL-6的分泌,但并没有改变IL-1β和TNF-α的表达量;Wnt5a上调了ALP的表达量及活性,促进了Ror2基因水平的表达,并上调了细胞内JNK蛋白水平。结论 Wnt5a通过调节成骨前体细胞OPG、IL-6、ALP和JNK的表达和分泌,可加重骨破坏和关节炎症,Wnt5a与类风湿关节炎(Rheumatoid arthritis,RA)骨破坏和关节炎症进展有关。     

CGRP和NPY 在大鼠股骨闭合骨折愈合不同阶段的变化及意义

目的:探讨交感神经分泌的神经肽Y(NPY)和感觉神经分泌的钙基因相关肽(CGRP)在体内骨折愈合的不同阶段的变化及意义。方法:选择6-8月龄的雄性大鼠,建立大鼠的股骨闭合骨折模型,术后2、4、8、12周取材。进行扫描电镜,免疫组织荧光染色和血清Elisa检测。结果:1骨折愈合不同时期感觉神经肽类物质CGRP和交感神经肽类物质NPY都有表达,且其含量有先增加后减少的趋势,并在骨折后8周含量达到最高。2骨折愈合不同阶段的大鼠血清感觉神经肽类物质CGRP和交感神经肽类物质NPY均呈上升趋势,差异有统计学意义(P0.05),且NPY的含量比CGRP的含量高。骨折后2-4周,CGRP含量增加较快;骨折后4-8周NPY含量增加较快。结论:骨折愈合的不同阶段,感觉神经肽类物质CGRP和交感神经肽类物质NPY含量先升后降,对不同阶段的骨形成及骨吸收产生影响。     

Organic Gallium Treatment Improves Osteoporotic Fracture Healing Through Affecting the OPG/RANKL Ratio and Expression of Serum Inflammatory Cytokines in Ovariectomized Rats

This study aimed to investigate the impact of organic gallium (OG) on osteoporotic fracture healing in ovariectomized female Sprague-Dawley rats, as well as study the mechanisms of OG on osteoporotic fracture healing. Forty-five female Sprague-Dawley rats were divided into three groups: sham operation group (Sxas control group), ovariectomized group (Ovx), and Ovx treated with OG group (Ovx + OG). Rat femoral fractures were studied using a standardized fracture-healing model utilizing bone fixation with an intramedullary pin. Six weeks later, analyses of micro-CT, histomorphometric, RNA extraction, RT-qPCR, and serum were performed following sacrifice of all mice. In comparison with Ovx group, OG can significantly increase bone volume (BV), tissue volume (TV), BV/TV radio, bone strength, callus bony area, and as similar to BMP-2 expression. OG treatment elevated OPG messenger RNA (mRNA) and inhibited RANKL mRNA, and showed an effect on OPG/RANKL ratio. OG treatment can inhibit the expression of TNF-α and IL-6. In conclusion, current study results indicate that organic OG can positively affect the OPG/RANKL ratio and inhibit the expression of serum inflammatory cytokines; thus, it can improve osteoporotic fracture healing.     

Effects of culture conditions on osteogenic differentiation in human mesenchymal stem cells

Human bone marrow-derived mesenchymal stem cells (hBMMSCs) must differentiate into osteogenic cells to allow for successful bone regeneration. In this study, we investigated the effects of different combinations of three soluble osteogenic differentiation-inducing factors [L-ascorbic acid (AC), beta-glycerophosphate (betaG), and bone morphogenic protein-2 (BMP-2)] and the presence of a hydroxyapatite (HA) substrate on hBMMSC osteogenic differentiation in vitro. hBMMSCs were cultured in medium containing various combinations of the soluble factors on culture plates with or without HA coating. After 7 days of culture, alkaline phosphatase (ALP) activity, calcium deposition, and osteoprotegerin (OPG) and osteopontin (OPN) expression were measured. The effects of individual and combined factors were evaluated using a factorial analysis method. BMP-2 predominantly affected expression of early markers of osteogenic differentiation (ALP and OPG). HA had the highest positive effect on OPN expression and calcium deposition. The interaction between AC, betaG, and HA had the second highest positive effect on ALP activity.     

Modulation of the effects of osteoprotegerin (OPG) ligand in a human leukemic cell line by OPG and calcitonin

The discovery of osteoprotegerin (OPG), osteoprotegerin ligand (OPGL), and RANK has elucidated the mechanism by which osteoblasts and stromal cells regulate osteoclastic differentiation and function and mediate the effects exerted by other hormones and cytokines. We have investigated the effects of these novel cytokines on the preosteoclastic cell line FLG 29.1. We show that OPGL alone and in combination with macrophage colony-stimulating factor (CSF-1) dramatically reduced replication and increased tartrate-resistant acid phosphatase activity. However, although FLG29.1 cells appear to adhere to the bone surface, they are not able to form resorption lacunae. OPG and calcitonin completely abolished the differentiation induced by OPGL. RANK was detectable in FLG 29.1 and the number of positive cells was increased by OPGL/CSF-1 treatment while reduced by calcitonin. We propose that calcitonin could interact with the OPG/OPGL, and its effects on RANK may explain in part the action of this hormone in suppressing bone resorption.     

Experimental study of the synergistic effect and network regulation mechanisms of an applied combination of BMP-2, VEGF,and TGF-β1 on osteogenic differentiation

The study aimed to explore the osteogenic effect induced by the combined use of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1), attain the best combination for osteogenic quality and efficiency, and explore the network regulation mechanisms of induced osteogenesis. MC3T3-E1 cells were cultured in vitro, and BMP-2, VEGF, and TGF β1 were added to osteogenic induction mediums in different combinations to conduct experiments. At 7 and 14 days, the alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining of the applied BMP-2 and VEGF combination were deeper and the quantitative analysis were higher than those of the other groups. After optimizing the time–effect relationship of the combined application, with BMP-2, VEGF, and TGF-β1 adding in the early stage and BMP-2 and VEGF adding in the late, the ALP and ARS staining of these groups were deeper and the quantitative analyses were meaningfully higher than the BMP-2 and VEGF combination group at 7 and 14 days. The expression of the RUNX2 gene and the Smad1 signaling pathway in the optimized combination group was also significantly higher. The results demonstrate that the combination of BMP-2, VEGF, and TGF-β1 applied according to the time–effect relationship can significantly promote osteogenic differentiation mainly through the classical BMP-receptor-Smad signal pathway.     

Bisphosphonates induce the osteogenic gene expression in co‐cultured human endothelial and mesenchymal stem cells

Bisphosphonates (BPs) are known to affect bone homeostasis and also to have anti-angiogenic properties. Because of the intimate relationship between angiogenesis and osteogenesis, this study analysed the effects of Alendronate (AL) and Zoledronate (ZL) in the expression of endothelial and osteogenic genes on interacting endothelial and mesenchymal stem cells, an issue that was not previously addressed. Alendronate and ZL, 10⁻¹²–10⁻⁶ M, were evaluated in a direct co-culture system of human dermal microvascular endothelial cells (HDMEC) and human bone marrow mesenchymal stem cells (HMSC), over a period of 14 days. Experiments with the respective monocultures were run in parallel. Alendronate and ZL caused an initial dose-dependent stimulation in the cell proliferation in the monocultures and co-cultures, and did not interfere with their cellular organization. In HDMEC monocultures, the expression of the endothelial genes CD31, VE-cadherin and VEGFR2 was down-regulated by AL and ZL. In HMSC monocultures, the BPs inhibited VEGF expression, but up-regulated the expression of the osteogenic genes alkaline phosphatase (ALP), bone morphogenic protein-2 (BMP-2) and osteocalcin (OC) and, to a greater extent, osteoprotegerin (OPG), a negative regulator of the osteoclastic differentiation, and increased ALP activity. In co-cultured HDMEC/HMSC, AL and ZL decreased the expression of endothelial genes but elicited an earlier and sustained overexpression of ALP, BMP-2, OC and OPG, compared with the monocultured cells; they also induced ALP activity. This study showed for the first time that AL and ZL greatly induced the osteogenic gene expression on interacting endothelial and mesenchymal stem cells.     

The effects of type I collagen on bone defects and gene expression changes for osteogenesis: In a rat model

The aim of this study is to investigate the effects of type I collagen on bone defects and on genes specifically for osteogenesis in a rat model. Two millimeter drill hole bone defect was created in the femur of rats. In the experimental group, type I collagen was applied in bone defects whereas in control group defects were left empty. Inflammation, development of connective tissue, osteogenesis, and foreign body reaction parameters evaluated with histologically and genes evaluated by blood samples. In the experimental group, the histopathologically significant change was found in favor of bone healing only at the first week. A significant increase was found in genetic expressions of BMP-1, 2, 3, 4, 5, 6, 7, TGF-βRII, Smad-1, IL-6, BMPR-IA, BMPR-IB, Eng, BMPR-II, c-fos, Cdkn1a, Chrd, Gdf-5, Id-1, PDGF-β, IGF-1, Serpine-1, and TGF-βRI at the first hour. At the first, third, and sixth week, no significant increase was found in any of the gene expressions. Type I collagen is found to be effective in favor of bone healing through increased inflammatory cytokines and expression of BMP genes in the early stages of fracture healing.     

全髋关节置换术用于股骨颈骨折患者的临床疗效评价及对血清OPG、BGP、ALP、CRP、IL-6的影响

目的:分析全髋关节置换术用于股骨颈骨折患者的临床效果及对血清骨保护素(OPG)、骨钙素(BGP)、碱性磷酸酶(ALP)、C反应蛋白(CRP)、白细胞介素-6(IL-6)的影响。方法:选择我院2014年3月~2016年3月收治的102例股骨颈骨折患者,按抽签法分为对照组与研究组,每组各51例。对照组采用半髋关节置换术治疗,研究组采用全髋关节置换术治疗。比较两组的临床疗效,治疗前后Harris评分、血清OPG、BGP、ALP、CRP、IL-6水平的变化及术后并发症的发生情况。结果:治疗后,研究组的优良率显著高于对照组(P0.05);两组Harris评分、血清OPG、BGP、ALP、CRP、IL-6水平均较治疗前显著上升,且研究组Harris评分显著高于对照组(P0.05),而两组OPG、BGP、ALP、CRP、IL-6水平比较差异无统计学意义(P0.05)。结论:全髋关节置换术用于股骨颈骨折的临床效果肯定,虽可引起血清OPG、BGP、ALP、CRP、IL-6水平上升,但未增加手术风险。     

Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria

The stimulators of bone resorption, prostaglandin E(2) (PGE(2)) and 1,25-dihydroxyvitamin D(3) (1,25D(3)), act through osteoblast-like cells to activate osteoclasts. One candidate for the intermediary produced by osteoblasts that subsequently stimulates the osteoclast is osteoprotegerin ligand (OPGL). OPGL has been shown to stimulate osteoclast differentiation and activation. The aim of the work reported here was to determine if soluble recombinant extracellular domain of human OPGL would bring about the change in osteoclast adhesion from the periosteum of mouse calvaria to the adjacent bone surface that occurs with the above-mentioned stimulators of resorption. This change in adherence or translocation of osteoclasts onto the bone surface required the expression and functioning of the integrin subunit, beta 3. We show that this soluble OPGL, like PGE(2) and 1,25D(3), stimulated the release of osteoclasts from the periosteum and their adherence to the bone surface accompanied by an increase in staining for immunolocalized integrin subunit beta 3. Recombinant human osteoprotegerin (OPG), which binds strongly to OPGL, inhibited this translocation of osteoclasts that occurred with PGE(2) and 1,25D(3), leaving integrin beta-3-negative osteoclasts on the periosteum. PGE(2) and 1,25D(3) increased the expression of messenger RNA for OPGL compared with indomethacin-treated controls after 6 h exposure. Evidence is presented that the change in the adhesion of osteoclasts from the periosteum to the bone surface, resulting in osteoclast activation, is mediated by OPGL.     

Mitogen limitation and bone morphogenetic protein-4 promote neurogenesis in SFME cells, an EGF-dependent neural stem cell line

Serum-free mouse embryo (SFME) cells are an epidermal growth factor (EGF)-dependent established line derived from brains of 16-d-old Balb/c mouse embryos. SFME cells grow indefinitely in serum-free medium without replicative senescence, chromosomal abnormalities, or malignant transformation. SFME cells express nestin, a neural stem cell marker, under serum-free conditions. Exposure to serum or transforming growth factor β (TGF-β) leads to a marked increase in differentiation toward the astrocytic lineage with expression of glial fibrillary acidic protein and other astrocyte markers. In this study, we show that treatment of SFME cells with bone morphogenetic protein-4 (BMP-4), another member of the TGF-β family, led to differentiation toward a neuronal lineage under conditions of low mitogenic stimulation (0.5 ng/mL) by EGF and fibroblast growth factor. Maximum mitogenic stimulation with 50 ng/mL EGF blocked the BMP-4 effect on neuronal differentiation, but did not block TGF-β-induced expression of markers of the astrocytic lineage. BMP-4 treatment also enhanced the activity of the neuron-specific enolase (NSE) promoter in SFME-NSE-lacZ cells that carry the gene for bacterial β-galactosidase under the control of the NSE promoter. Extended BMP-4 treatment caused SFME cells to express a neuronal phenotype synthesizing gamma-aminobutyric acid. These results indicate that SFME cells have the capacity to generate both neurons and astrocytes in vitro, which resemble the behavior of EGF-dependent multipotential stem cells in the central nervous system, and establish a relationship between effects of BMP-4 and degree of mitogenic stimulation by other peptide growth factors.