Bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium

AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)group.The cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell chamber.The EMT-related indexes and BMP-6 protein levels were detected by Western blotting.Furthermore,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression group.The EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were detected.RESULTS:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly enhanced.TGF-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in RPE.Similarly,the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced.BMP-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

基于BMP-2/BMP-7机制探讨生龙接骨胶囊预防老年骨质疏松性胸腰椎骨折术后再发性骨折的作用

目的探讨生龙接骨胶囊对老年骨质疏松性胸腰椎骨折(OTF)术后再发性骨折的作用,并基于骨形态发生蛋白-2/骨形态发生蛋白-7(BMP-2/BMP-7)机制初步分析其作用机制。方法选取2020年1月至2022年10月在南昌市洪都中医院收治的100例行经皮椎体成形术(PVP)的老年OTF患者为研究对象,按随机数字表法分为常规组(50例)和胶囊组(50例)。常规组采用常规的PVP治疗,胶囊组患者在常规组基础上服用生龙接骨胶囊治疗。比较两组患者椎体结构(Cobb角和伤椎椎体前缘高度比)、治疗前后血清BMP-2、BMP-7水平、骨代谢指标[骨特异性碱性磷酸酶(BALP)、Ⅰ型原胶原N端前肽(PⅠNP)、骨钙素(OST)]、骨密度(BMD)、康复情况[Oswestry腰椎功能障碍指数(ODI)]评估、疼痛等级[视觉模拟评分法(VAS)]评分、临床有效率、椎体再骨折发生率和不良反应发生情况。结果治疗后,两组患者Cobb角改善,伤椎椎体前缘高度比优于治疗前,胶囊组均优于常规组,差异有统计学意义(P<0.05);胶囊组的BMP-2、BMP-7表达量高于常规组,差异有统计学意义(P<0.05);患者术后再发性骨折情况均良好,胶囊组愈合速度快于常规组,差异有统计学意义(P<0.05);治疗后,胶囊组的BALP、PⅠNP、OST均高于常规组,差异有统计学意义(P<0.05);两组患者的BMD高于治疗前,且胶囊组高于常规组,ODI评分、VAS评分均低于治疗前,且胶囊组低于常规组,差异有统计学意义(P<0.05);胶囊组的临床总有效率(95.0%)高于常规组(80.0%),胶囊组的再骨折发生率(4%)低于常规组(18%),差异有统计学意义(P<0.05);两组患者均未见明显不良反应。结论生龙接骨胶囊能通过上调患者血清BMP-2、BMP-7水平,改善BMD从而预防老年OTF的术后再发性骨折,其机制可能与生龙接骨胶囊能刺激BMP信号通路,加速成骨细胞分化有关。

FGF2和BMP-2对Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后的预测价值

目的探讨成纤维细胞生长因子2(FGF2)和骨形态发生蛋白-2(BMP-2)对Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后的预测价值。方法前瞻性选取2020年1月—2021年12月在新疆医科大学第一附属医院住院治疗的105例Ⅲ、Ⅳ型慢性骨髓炎患者作为研究对象,均接受病灶清除联合封闭负压引流治疗,按不同治疗预后分为疗效好组75例(71.4%)和疗效差组30例(28.6%)。比较两组患者的临床资料、血清炎症因子、FGF2及BMP-2表达水平;采用多因素Logistic回归分析影响患者预后的独立危险因素,分析FGF2及BMP-2与预后的关系;构建相关列线图模型,绘制受试者工作特征(ROC)曲线和决策曲线,分析FGF2、BMP-2及联合预测模型的预测效能和净收益率。结果疗效差组Ⅳ型Cierny-Mader分型及窦道形成患者占比高于疗效好组(P<0.05)。疗效差组患者术前红细胞沉降率(ESR)、C反应蛋白(CRP)及肿瘤坏死因子-α(TNF-α)水平均高于疗效好组(P<0.05),疗效差组患者术前FGF2及BMP-2水平均低于疗效好组(P<0.05)。多因素Logistic回归分析结果显示,Cierny-Mader分型[O^R=5.036(95%CI:1.369,9.894)]、窦道形成[O^R=2.987(95%CI:1.156,7.247)]、FGF2[O^R=0.446(95%CI:0.129,0.735)]和BMP-2[O^R=0.485(95%CI:0.212,0.738)]为影响Ⅲ、Ⅳ型慢性骨髓炎患者预后的危险因素(P<0.05)。基于FGF2、BMP-2构建预测预后的列线图模型,校准曲线显示,Ⅲ、Ⅳ型慢性骨髓炎患者治疗疗效的预测值与实际观测值十分接近;ROC曲线分析结果显示,Cierny-Mader分型、窦道形成、FGF2及BMP-2预测预后的曲线下面积分别为0.783(95%CI:0.754,0.875)、0.752(95%CI:0.761,0.893)、0.823(95%CI:0.789,0.885)及0.811(95%CI:0.797,0.875),FGF2及BMP-2的最佳截断值分别为18.9 ng/L和113.5 ng/L,4者联合预测的曲线下面积为0.952(95%CI:0.896,0.991);决策曲线分析结果显示,Cierny-Mader分型、窦道形成、FGF2及BMP-2预测预后均具有良好的净收益率,并且联合预测的总体净收益率高于单一指标。结论基于Cierny-Mader分型、窦道形成、FGF2及BMP-24个指标构建的列线图模型能准确预测Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后。

骨质疏松症患者PINP、25-(OH)VitD_(3)、BMP-2与中医辨证分型的相关性研究

目的:分析骨质疏松症患者血清总I型胶原氨基末端前肽(PINP)、25-羟维生素D3[25-(OH)VitD_(3)]及骨形态发生蛋白2(BMP-2)与其中医辨证分型的相关性。方法:收集我院2020年8月~2023年8月医院收治的157例骨质疏松症患者的一般资料及中医四诊资料进行回顾性分析,并统计骨质疏松症患者中医辨证分型结果,对不同症型患者基本资料、PINP、25-(OH)VitD_(3)、BMP-2水平进行比较。结果:157例骨质疏松症患者中医辨证分型属肾阳虚证34例,脾肾阳虚证43例,肝肾阴虚证49例,血瘀气滞证31例。不同中医辨证分型的骨质疏松患者血清PINP、25-(OH)VitD_(3)及BMP-2水平整体相比,差异有统计学意义(P<0.05);其中,血瘀气滞组PINP水平显著高于肾阳虚组、脾肾阳虚组及肝肾阴虚组患者(P<0.05),而其余3组两两间相比,差异无统计学意义(P>0.05);脾肾阳虚证患者25-(OH)VitD_(3)水平明显低于肾阳虚组、肝肾阴虚组及血瘀气滞组(P<0.05),且肾阳虚组低于肝肾阴虚组及血瘀气滞组(P<0.05),而其余两组相比差异无统计学意义(P>0.05);血瘀气滞组BMP-2水平显著低于肾阳虚组、脾肾阳虚组及肝肾阴虚组患者(P<0.05),而其余3组两两间相比,差异无统计学意义(P>0.05);二分类logistics回归分析结果显示,血瘀气滞与PINP呈正相关(P<0.05),与BMP-2呈负相关(P<0.05);脾肾阳虚与25-(OH)VitD_(3)呈负相关(P<0.05)。结论:骨质疏松症患者的血清PINP、25-(OH)VitD_(3)、BMP-2水平与其中医辨证分型具有一定相关性,可作为评估患者中医辨证分型的参考指标。

DSPP与BMP-2在牙髓干细胞修复再生牙髓牙本质复合体中的表达及意义

目的 探讨牙本质涎磷蛋白(dentin sialophosphoprotein,DSPP)与骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)在第三代同质异体牙髓干细胞(dental pulp stem cell,DPSCs)再生修复牙髓牙本质复合体后的表达和意义,为年轻恒牙牙髓根尖周疾病提供新的诊疗思路。方法 18只SD大鼠随机分为实验组和对照组,两组均在全麻下摘除大鼠上颌双侧第一磨牙冠髓,实验组同期髓腔定植体外培养的同质异体大鼠牙髓干细胞,对照组冠髓摘除后不进行任何处理,术后均使用玻璃离子充填封闭髓腔。两组动物均于术后2、4、6周处死,取其上颌骨进行免疫组织化学方法检测DSPP和BMP-2的表达。结果 术后2、4、6周时,实验组牙髓牙本质复合体处的DSPP、BMP-2的表达水平均高于对照组,差异有统计学意义(P<0.05)。结论 同质异体牙髓干细胞再植后会增加牙髓牙本质复合体处的DSPP和BMP-2的表达,有助于修复再生牙髓牙本质复合体。

TGF-β、BMP-2、VEGF和PDGF在骨折愈合过程中的作用

骨折延迟愈合及不愈合是临床需要解决的一大难题,骨愈合过程被证实与生长因子紧密联系。本文对骨愈合过程中活跃的生长因子,如转化生长因子-β、骨形态发生蛋白-2、血管内皮生长因子和血小板源性生长因子可能的作用机制、影响因素和治疗应用进行综述,以期为临床应用提供参考依据。

The Effect of Simvastatin on mRNA Expression of Transforming Growth Factor-β1,Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor in Tooth Extraction Socket

Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.

Drilling Combined with Adipose-derived Stem Cells and Bone Morphogenetic Protein-2 to Treat Femoral Head Epiphyseal Necrosis in Juvenile Rabbits

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells （ADSCs） and bone morphogenetic protein-2 （BMP-2） to treat femoral head epiphyseal ischemic necrosis, which can be done in juvenile rabbits. Passagefour bromodeoxyuridine （BrdU）-labeled ADSCs were cultured, assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability. Twomonth-old, healthy male rabbits （1.2 to 1.4 kg, n=45） underwent ischemic induction and were randomly divided into five groups （group A： animal model control; group B： drilling; group C： drilling ＆ ADSCs; group D： drilling ＆ BMP-2; and group E： drilling ＆ ADSCs ＆ BMP-2）. Magnetic resonance imaging （MRI）, X-ray imaging, hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4, 6 and 10 weeks after treatment. Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability. Similar results were observed in the rabbits in groups C and E at weeks 6 and 10. The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B （P〈0.01）. Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B （P〈0.05）. In summary, drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

Chondrogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells Induced by Cartilage-derived Morphogenetic Protein-2 In Vitro

To study the cartilage differentiation of mouse mesenchymal stem cells （MSCs） induced by cartilage-derived morphogenetic proteins-2 in vitro, the MSCs were isolated from mouse bone marrow and cultured in vitro. The cells in passage 3 were induced into chondrogenic differentiation with different concentrations of recombinant human cartilage-derived morphogenetic proteins-2 （0, 10, 20, 50 and 100 ng/mL）. After 14 days of induction, morphology of cells was observed under phase-contrast microscope. Collagen Ⅱ mRNA and protein were examined with RT-PCR, Western blotting and immunocytochemistry respectively and the sulfate glycosaminoglycan was measured by Alcian blue staining. RT-PCR showed that CDMP-2 could promote expression of collagen Ⅱ mRNA in an dose-dependant manner, especially at the concentration of 50 ng/mL and 100 ng/mL. Immunocytochemistry and Western blotting revealed a similar change. Alcian blue staining exhibited deposition of typical cartilage extracellular matrix. Our results suggest that mouse bone marrow mesencymal stem cells can differentiate into chondrogenic phonotype with the induction of CDMP-2 in vitro, which provides a basis for further research on the role of CDMP-2 in chondrogenesis.

Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

AIM: To characterize the expression and dynamic changes of bone morphogenetic protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS: Fifty-four adult male Wistar rats were randomly divided into three groups: A normal control (NC) group, a partial hepatectomized (PH) group and a sham operated (SO) group. To study the effect of liver regeneration on BMP-2 expression, rats were sacrificed before and at different time points after PH or the sham intervention (6, 12, 24 and 48 h). For each time point, six rats were used in parallel. Expression and distribution of BMP-2 protein were determined in regenerating liver tissue by Western blot analysis and immunohistochemistry. Effects of BMP-2 on cell proliferation of human Huh7 hepatoma cell line were assessed using an MTT assay.RESULTS: In the normal liver strong BMP-2 expression was observed around the central and portal veins. The expression of BMP-2 decreased rapidly as measured by both immunohistochemistry and Western blot analysis. This decrease was at a maximum of 3.22 fold after 12 h and returned to normal levels at 48 h after PH. No significant changes in BMP-2 immunoreactivity were observed in the SO group. BMP-2 inhibited serum induced Huh7 cell proliferation.CONCLUSION: BMP-2 is expressed in normal adult rat liver and negatively regulates hepatocyte proliferation. The observed down regulation of BMP-2 following partial hepatectomy suggests that such down regulation may be necessary for hepatocyte proliferation.

Use of recombinant human bone morphogenetic protein-2 in spine surgery

Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedicsurgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially approved by the United States Food and Drug Administration only for single level anterior lumbar interbody fusion, nevertheless it is widely used by many surgeons with off-label indications. Despite advantages in bone formation, its use still remains a controversial issue and several complications have been described by authors who oppose their wide use.

Regulation of scleral fibroblast differentiation by bone morphogenetic protein-2

Bone morphogenesis proteins(BMPs) are multi-functional growth factors. They are expressed in retina,retinal pigment epithelium(RPE) and sclera and serve as a regulator in the growth and development of the eye. This article reviewed the chondrogenic potency of the sclera,biochemical and pathological changes of myopic scleral tissue and the differentiation of chondrogenesis by BMP-2. We proposed the hypothesis that BMP-2 can regulate differentiate of scleral fibroblasts and affect the development of myopia.

骨质疏松性椎体压缩性骨折患者血清BMP-2,Runx2水平对术后骨折延迟愈合的预测价值

目的探讨骨质疏松性椎体压缩性骨折(Osteoporotic vertebral compressibility fracture,OVCF)患者血清骨形态发生蛋白-2(Bone morphogenetic protein-2,BMP-2)、核心结合因子2(Runt-related transcription factor 2,Runx2)水平对术后骨折延迟愈合的预测价值。方法选取2020年1月-2023年4月徐州医科大学附属淮安医院骨科收治的260例OVCF患者为研究对象,均采用经皮椎体成形术(Percutaneous vertebroplasty,PVP)或椎体后凸成形术(Percutanous kyphoplasty,PKP)治疗,根据术后3个月骨折愈合情况分延迟愈合组、正常愈合组。分析OVCF患者术后骨折延迟愈合的影响因素及血清BMP-2,Runx2水平对术后骨折延迟愈合的预测价值。绘制决策曲线和临床影响曲线,评价血清BMP-2,Runx2水平对术后骨折延迟愈合的价值。结果260例患者术后无失访,22例出现骨折延迟愈合,发生率为8.46%(22/260)。延迟愈合组年龄、吸烟比率、合并糖尿病比率、合并甲状腺疾病比率、有椎体裂隙征比率大于正常愈合组,骨密度T值、术前和术后3个月血清BMP-2,Runx2水平小于正常愈合组,差异有统计学意义(P<0.05)。合并糖尿病、有椎体裂隙征是OVCF患者术后骨折延迟愈合的独立危险因素,骨密度T值、BMP-2,Runx2是OVCF患者术后骨折延迟愈合的独立保护因素(P<0.05)。BMP-2,Runx2联合预测OVCF患者术后骨折延迟愈合对应AUC值为0.856。阈值在0.10~0.63范围内,BMP-2,Runx2联合评估模型评估OVCF患者术后骨折延迟愈合的净受益率优于单独检测。在阈值概率为0.26时,被该模型划分入高风险的人数与真阳性人数基本达成一致。结论OVCF患者血清BMP-2,Runx2水平降低,二者联合检测对术后骨折延迟愈合具有较高的预测效能。

BMP-2联合雷奈酸锶对大鼠骨髓间充质干细胞成骨分化的影响

目的:研究骨形态发生蛋白2(bone morphogenetic protein-2,BMP-2)联合雷奈酸锶(strontium ranelate,Sr)对大鼠骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)成骨分化的影响,并探讨其相关机制。方法:取对数期大鼠BMSCs,随机分为对照组(不采用任何诱导液处理)、BMP-2组(0.1 mg/L BMP处理)、Sr组(5 mmol/L Sr处理)、BMP-2+Sr组(采用0.1 mg/L BMP处理6天后换液,再加入5 mmol/L Sr处理)。利用MTT实验检测BMSCs增殖情况,硝基苯磷酸盐法检测碱性磷酸酶(alkaline phosphatase,ALP)活性,茜素红染色观察矿化情况,Western免疫印迹法检测TGF-β1、Smad2、p-Smad2及Runx2蛋白表达。采用SPSS 24.0软件包对数据进行统计学分析。结果:与对照组相比,BMP-2组、Sr组、BMP-2+Sr组ALP活性增强,MTT实验吸光度值、矿化面积百分比及TGF-β1、Runx2蛋白表达量,p-Smad2/Smad2水平显著升高(P<0.05)。与BMP-2组、Sr组相比,BMP-2+Sr组ALP活性增强,MTT实验吸光度值、矿化面积百分比及TGF-β1、Runx2蛋白表达量,p-Smad2/Smad2水平显著升高(P<0.05)。结论:BMP-2联合Sr可促进大鼠BMSCs增殖及成骨分化,其作用机制可能与激活TGF-β1/Smad信号通路有关。

血清BMP-2、N-MID水平与老年股骨粗隆间骨折患者术后髋关节功能不良的关系研究

目的分析血清骨形态发生蛋白2(BMP-2)、骨钙素N端中分子片段(N-MID)水平与老年股骨粗隆间骨折患者术后髋关节功能不良的关系。方法选取2022年2月至2023年6月在该院治疗的96例老年股骨粗隆间骨折患者,根据患者术后髋关节功能的Harris评分结果分为术后良好组(n=67)和术后不良组(n=29)。收集所有患者的临床资料,检测血清BMP-2、N-MID水平并进行比较;采用多因素Spearman法分析血清BMP-2、N-MID水平与患者术后髋关节功能不良的关系;患者术后髋关节功能不良的影响因素采用多因素Logistic回归分析;血清BMP-2、N-MID水平对患者术后髋关节功能不良的预测价值用受试者工作特征(ROC)曲线进行分析。结果术后良好组与术后不良组患者的骨折Evans-Jensen分型、有无术后并发症、术后内固定方式、骨质疏松分级比较,差异有统计学意义(P<0.05);术后不良组血清BMP-2、N-MID水平显著低于术后良好组,差异有统计学意义(P<0.05);老年股骨粗隆间骨折患者血清BMP-2、N-MID水平与术后髋关节功能均呈负相关(r=-0.564、-0.638,P<0.05);骨折Evans-Jensen分型Ⅲ~Ⅴ型、有术后并发症、骨质疏松分级4~6级均是老年股骨粗隆间骨折患者术后髋关节功能不良的危险因素(P<0.05),血清BMP-2、N-MID水平升高是其保护因素(P<0.05);血清BMP-2、N-MID、两者联合预测患者术后髋关节功能不良的曲线下面积(AUC)分别为0.932、0.883、0.977,联合预测价值更高(Z_(两者联合-BMP-2)=2.220,P=0.026;Z_(两者联合-N-MID)=3.162,P=0.002)。结论老年股骨粗隆间骨折术后髋关节功能不良患者血清BMP-2、N-MID水平显著降低,与患者术后髋关节功能呈负相关,两者联合能更好地预测患者术后髋关节功能不良。

急慢性牙髓炎患者血清PGE2、BMP-2表达及其对病情转归的影响

目的分析急慢性牙髓炎患者血清前列腺素E2(PGE2)、骨形态发生蛋白-2(BMP-2)表达及其对病情转归的影响。方法选择2020年6月至2023年5月安徽寿县人民医院收治的110例牙髓炎患者作为研究对象,其中急性牙髓炎50例(急性组),慢性牙髓炎60例(慢性组),根据疾病治疗转归情况分为预后不良组(n=26)、预后良好组(n=84)。另选取同期体检健康者76名作为对照组。采用酶联免疫吸附法检测所有研究对象血清PGE2、BMP-2表达水平。采用受试者工作特征曲线(ROC)评估血清PGE2、BMP-2对急慢性牙髓炎患者疾病转归的诊断价值,采用多因素Logistic回归分析影响急慢性牙髓炎患者疾病转归的因素。结果血清PGE2水平:急性牙髓炎组>慢性牙髓炎组>对照组,BMP-2水平:急性牙髓炎组<慢性牙髓炎组<对照组,差异有统计学意义(P<0.05)。预后不良组血清CRP、TNF-α、PGE2水平均高于预后良好组,血清BMP-2低于预后良好组,差异有统计学意义(P<0.05)。ROC曲线分析显示,血清PGE2、BMP-2及二者联合评估急慢性牙髓炎患者疾病转归的AUC分别为0.833(95%CI:0.783~0.883)、0.866(95%CI:0.816~0.916)、0.914(95%CI:0.864~0.964)。多因素分析显示,血清CRP>644.42 mg/L(OR=2.675,95%CI:1.701~4.207)、TNF-α>57.73 ng/mL(OR=2.779,95%CI:1.689~4.571)、PGE2>133.45 pg/m(OR=4.154,95%CI:2.116~8.152)、BMP-2≤89.73 g/L(OR=3.501,95%CI:1.987~6.168)均为影响急慢性牙髓炎患者预后不良的危险因素(P<0.05)。结论急慢性牙髓炎患者血清PGE2水平升高,BMP-2水平降低,二指标水平与疾病转归密切相关,可作为评估急慢性牙髓炎患者疾病转归的生物学标志物。

三联疗法对膝骨关节炎疗效及对血清BMP-2、软骨寡聚体蛋白和炎症因子水平的影响

目的:探究左归丸、富血小板血浆(PRP)、间充质干细胞(MSCs)三联疗法对膝骨关节炎患者的治疗效果及对患者血清骨形态发生蛋白-2(BMP-2)、软骨寡聚基质蛋白(COMP)与血清炎症因子[白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、C反应蛋白(CRP)水平]的影响。方法:选取2022年4月—2023年1月在新余市人民医院接受治疗的98例膝骨关节炎患者,按照随机抽签法将患者分入对照组和观察组,各49例。对照组接受膝骨关节炎的常规治疗,观察组在此基础上加用左归丸、PRP、MSCs三联疗法。对两组治疗前后中医证候积分、奎森功能演算指数(Lequesne)、西安大略和麦克马斯特大学骨关节炎指数(WOMAC)评分、BMP-2、COMP、IL-6、IL-17、CRP水平、疗效进行对比。结果:治疗后,与对照组相比,观察组中医证候各项积分、Lequesne评分、WOMAC评分、COMP、IL-6、IL-17、CRP水平均较低(P<0.05),BMP-2水平较高(P<0.05),疗效更优(P<0.05)。结论:左归丸、PRP、MSCs三联疗法有良好的治疗效果,可更有效地改善患者膝关节功能,缓解疾病带来的不适,提高患者生活水平。

股骨近端防旋髓内钉内固定联合BMP-2植骨治疗老年股骨转子间粉碎型骨折的临床效果

目的探讨股骨近端防旋髓内钉内固定(Proximal Femoral Nail Antirotation,PFNA)联合骨形态发生蛋白-2(Bone Morphogenetic Protein-2,BMP-2)植骨治疗老年患者股骨转子间粉碎性骨折的临床效果。方法回顾性选取2015年8月—2020年3月莆田市第一医院骨科收治的80例股骨转子间骨折老年患者的临床资料,依据手术方法不同分为PFNA组(42例)和PFNA+BMP-2植骨组(38例)。比较两组手术时间、术中出血量、术后开始负重行走时间、骨折愈合时间以及两组术后2周、3个月、9个月髋关节功能评分。结果PFNA+BMP-2植骨组骨折愈合时间、开始下地负重行走时间分别为(12.47±1.88)周和(12.64±1.95)周,均明显短于PFNA组的(14.40±2.35)周、(13.36±2.37)周,差异有统计学意义(t=4.028、4.048,P均<0.05)。PFNA+BMP-2植骨组在术后3、9个月髋关节功能评分分别为(88.31±5.98)分和(91.38±4.66)分,均高于PFNA组的(82.86±7.17)分和(86.92±5.65)分,差异有统计学意义(t=3.670、3.828,P均<0.05)。结论PFNA联合BMP-2植骨治疗老年患者股骨转子间粉碎型骨折可以取得良好的疗效,特别适用于骨质疏松性老年患者股骨转子间骨折的治疗,是一种安全、有效的治疗方法。

Three-dimensional kagome structures in a PCL/HA-based hydrogel scaffold to lead slow BMP-2 release for effective bone regeneration

Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site,or if the bone tissue is in poor condition.Thus,an effective bone graft in terms of both osteoconductivity and osteoinductivity is required for clinical therapy.Recently,the three-dimensional(3D)kagome structure has been shown to be advantageous for bone tissue regeneration due to its mechanical properties.In this study,a polycaprolactone(PCL)kagome-structure scaffold containing a hyaluronic acid(HA)-based hydrogel was fabricated using a 3D printing technique.The retention capacity of the hydrogel in the scaffold was assessed in vivo with a rat calvaria subcutaneous model for 3 weeks,and the results were compared with those obtained with conventional 3D-printed PCL grid-structure scaffolds containing HA-based hydrogel and bulk-type HA-based hydrogel.The retained hydrogel in the kagome-structure scaffold was further evaluated by in vivo imaging system analysis.To further reinforce the osteoinductivity of the kagome-structure scaffold,a PCL kagome-structure scaffold with bone morphogenetic protein-2(BMP-2)containing HA hydrogel was fabricated and implanted in a calvarial defect model of rabbits for 16 weeks.The bone regeneration characteristics were evaluated with hematoxylin and eosin(H&E),Masson’s trichrome staining,and micro-CT image analysis.

Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate

BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.