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 osteocond...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.展开更多
二膦酸盐不仅特异性抑制破骨细胞,同时对成骨细胞也起一定的作用.用酶消化法取乳鼠颅盖骨进行成骨细胞培养,分为空白对照组、阿仑膦酸钠高、中、低剂量组.从BMP-2/Smads/Runx2/Osterix信号通路角度观察二膦酸盐对成骨细胞分化的作用.结...二膦酸盐不仅特异性抑制破骨细胞,同时对成骨细胞也起一定的作用.用酶消化法取乳鼠颅盖骨进行成骨细胞培养,分为空白对照组、阿仑膦酸钠高、中、低剂量组.从BMP-2/Smads/Runx2/Osterix信号通路角度观察二膦酸盐对成骨细胞分化的作用.结果显示:比色法结果显示干预2和4d后各剂量阿仑膦酸钠组的碱性膦酸酶(AKP)显著增加,其中中剂量组表达最高,各组明显高于空白对照组(p<0.05),第6天各剂量阿仑膦酸钠组AKP逐渐下降,与空白对照组比较,无统计学意义(p>0.05);ELISA结果显示随着天数增加各剂量阿仑膦酸钠组的BMP-2逐渐增加,其中中剂量组表达最高,各组明显高于空白对照组(p<0.05),干预2和4d后各剂量阿仑膦酸钠组的I型胶原(Collagen Type I)显著增加,其中中剂量组表达最高,各组明显高于空白对照组(p<0.05),第6天各剂量阿仑膦酸钠组Collagen Type I逐渐下降,空白对照组随着天数逐渐增加,但均低于同时期用药组(p<0.05);荧光定量PCR(qPCR)检测结果显示BMP-2、Smad1/5、Runx2和Osterix mRNA表达在干预后,随着时间的延长,逐渐上升;阿仑膦酸钠组的含量高于同期的空白对照组.提示阿伦膦酸钠能刺激成骨细胞增殖,增强BMP、AKP活性,通过BMP-2/Smads/Runx2/Osterix通路上调相关基因表达,促进成骨细胞分化.展开更多
目的观察家兔膝骨关节炎模型关节软骨BMP-2/gremlin的表达情况及补肾活血方的调节作用。方法 48只实验用家兔随机分为治疗组、阳性对照组和阴性对照组,每组16只。治疗组和阳性对照组行右膝关节前交叉韧带横断手术(ACLT)造模,阴性对照组...目的观察家兔膝骨关节炎模型关节软骨BMP-2/gremlin的表达情况及补肾活血方的调节作用。方法 48只实验用家兔随机分为治疗组、阳性对照组和阴性对照组,每组16只。治疗组和阳性对照组行右膝关节前交叉韧带横断手术(ACLT)造模,阴性对照组行右膝模拟造模手术。治疗组造模后给予补肾活血方灌胃治疗,阳性对照组造模后给予制动干预,阴性对照组行模拟手术后给予生理盐水灌胃。在术后第4、8周各组各处死8只家兔,观察膝关节损伤软骨肉眼改变,取组织标本经石蜡包埋切片后行常规苏木精-伊红染色观察软骨组织的病理变化,Real time PCR法及免疫组化法检测BMP-2、gremlin的表达。结果补肾活血方可减轻兔膝骨关节炎模型关节软骨形态学损害。治疗组和阳性对照组第4、8周软骨中BMP-2及gremlin表达量明显高于阴性对照组(P<0.05),且阳性对照组较治疗组gremlin同期表达增多(P<0.05);第8周阳性对照组标本中BMP-2表达持续稳定,但gremlin表达水平较第4周明显上升(P<0.05)。结论补肾活血方对兔ACLT模型关节软骨中修复保护性细胞因子BMP-2的表达有上调作用,同时抑制BMP-2拮抗因子gremlin过度表达,对骨关节炎修复有良好的调节作用。展开更多
基金supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),the Ministry of Health&Welfare,Republic of Korea(Grant Number:HI14C2143)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MIST)(NRF-2021R1A2C2009665)。
文摘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.
文摘二膦酸盐不仅特异性抑制破骨细胞,同时对成骨细胞也起一定的作用.用酶消化法取乳鼠颅盖骨进行成骨细胞培养,分为空白对照组、阿仑膦酸钠高、中、低剂量组.从BMP-2/Smads/Runx2/Osterix信号通路角度观察二膦酸盐对成骨细胞分化的作用.结果显示:比色法结果显示干预2和4d后各剂量阿仑膦酸钠组的碱性膦酸酶(AKP)显著增加,其中中剂量组表达最高,各组明显高于空白对照组(p<0.05),第6天各剂量阿仑膦酸钠组AKP逐渐下降,与空白对照组比较,无统计学意义(p>0.05);ELISA结果显示随着天数增加各剂量阿仑膦酸钠组的BMP-2逐渐增加,其中中剂量组表达最高,各组明显高于空白对照组(p<0.05),干预2和4d后各剂量阿仑膦酸钠组的I型胶原(Collagen Type I)显著增加,其中中剂量组表达最高,各组明显高于空白对照组(p<0.05),第6天各剂量阿仑膦酸钠组Collagen Type I逐渐下降,空白对照组随着天数逐渐增加,但均低于同时期用药组(p<0.05);荧光定量PCR(qPCR)检测结果显示BMP-2、Smad1/5、Runx2和Osterix mRNA表达在干预后,随着时间的延长,逐渐上升;阿仑膦酸钠组的含量高于同期的空白对照组.提示阿伦膦酸钠能刺激成骨细胞增殖,增强BMP、AKP活性,通过BMP-2/Smads/Runx2/Osterix通路上调相关基因表达,促进成骨细胞分化.
文摘目的观察家兔膝骨关节炎模型关节软骨BMP-2/gremlin的表达情况及补肾活血方的调节作用。方法 48只实验用家兔随机分为治疗组、阳性对照组和阴性对照组,每组16只。治疗组和阳性对照组行右膝关节前交叉韧带横断手术(ACLT)造模,阴性对照组行右膝模拟造模手术。治疗组造模后给予补肾活血方灌胃治疗,阳性对照组造模后给予制动干预,阴性对照组行模拟手术后给予生理盐水灌胃。在术后第4、8周各组各处死8只家兔,观察膝关节损伤软骨肉眼改变,取组织标本经石蜡包埋切片后行常规苏木精-伊红染色观察软骨组织的病理变化,Real time PCR法及免疫组化法检测BMP-2、gremlin的表达。结果补肾活血方可减轻兔膝骨关节炎模型关节软骨形态学损害。治疗组和阳性对照组第4、8周软骨中BMP-2及gremlin表达量明显高于阴性对照组(P<0.05),且阳性对照组较治疗组gremlin同期表达增多(P<0.05);第8周阳性对照组标本中BMP-2表达持续稳定,但gremlin表达水平较第4周明显上升(P<0.05)。结论补肾活血方对兔ACLT模型关节软骨中修复保护性细胞因子BMP-2的表达有上调作用,同时抑制BMP-2拮抗因子gremlin过度表达,对骨关节炎修复有良好的调节作用。
