腺病毒介导NELL1促进骨溶解后的高质量骨再生Adenovirus-mediated NELL1 promotes bone regeneration in calvarial osteolysis model
郭旭;彭江;王玉;赵斌;袁玫;孟昊业;张莉;张新立;许文静;汪爱媛;卢世璧;
摘要(Abstract)：
[目的]研究具有特异性成骨作用的NELL1因子对磨屑所致骨溶解的影响,为骨溶解病的治疗提供一种新方案。[方法]建立聚乙烯(Polyethylene,PE)颗粒诱导的颅骨骨溶解模型,68只Balb/c小鼠随机分成4组,即假手术组:术后1 d颅顶皮下注射0.1 ml生理盐水;颗粒对照组:植入10 mg PE颗粒,术后1 d注射0.1 ml生理盐水;实验组(Ad-GFP-NELL1组):植入10 mg PE颗粒,术后1 d注射0.1 ml(109 pfu)NELL1荧光重组腺病毒载体(Ad-GFP-NELL1);安慰剂组(Ad-GFP组):植入10 mg PE颗粒,术后1 d注射0.1 ml(109pfu)荧光重组腺病毒载体(Ad-GFP)。术后10 d采用活体荧光成像检测NELL1及GFP表达情况,并于处死后进行Micro-CT、组织学及生物力学的检测。[结果]活体荧光证实实验组与安慰剂组小鼠颅顶有NELL1及GFP的高度表达,Micro-CT 3D图像观察实验组小鼠的颅骨骨溶解所致骨量丢失明显减少,所选兴趣区(ROI)的骨体积(BV)、骨密度(BMD)、骨小梁厚度(Tb.Th.3D)、骨表面积体积比(BS/BV)均明显优于对照组及安慰剂组。组织学切片观察到实验组的骨再生明显增多。另外,实验组小鼠的颅骨弹性模量[(2.50±0.12)MPa]也明显优于对照组[(0.60±0.20)MPa]及安慰剂组[(0.82±0.09)MPa](OP<0.01)。[结论]腺病毒介导表达的成骨因子NELL1能通过促进高质量的骨再生平衡磨屑所致骨溶解的骨量丢失,是治疗骨溶解的一种潜在性解决方案。
关键词(KeyWords)： NELL1;骨溶解;磨屑;骨再生;Micro-CT
基金项目(Foundation): 国家自然科学基金资助项目(编号:30872621)国家自然科学基金项目(编号:30872633);; 国家863主题项目(编号:2012AA020502)
作者(Author): 郭旭;彭江;王玉;赵斌;袁玫;孟昊业;张莉;张新立;许文静;汪爱媛;卢世璧;
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