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首页> 外文期刊>Spine >Potential use of Sox9 gene therapy for intervertebral degenerative disc disease.
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Potential use of Sox9 gene therapy for intervertebral degenerative disc disease.

机译：Sox9基因疗法在椎间盘退变性疾病中的潜在用途。

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STUDY DESIGN: A new recombinant adenoviral vector expressing Sox9, a chondrocyte-specific transcription factor, was tested in a chondroblastic cell line and primary human intervertebral disc cells in vitro. Direct infection of intervertebral disc cells then was assessed in a rabbit model. OBJECTIVES: To deliver a potentially therapeutic viral vector expressing Sox9 to degenerative human and rabbit intervertebral discs cells, and to assess the effect of Sox9 expression on Type 2 collagen production. SUMMARY OF THE BACKGROUND DATA: The concentration of competent Type 2 collagen, an essential constituent of the healthy nucleus pulposus, declines with intervertebral disc degeneration. Recent studies suggest that Sox9 upregulates Type 2 collagen production. Interventions that augment Type 2 collagen production by intervertebral disc cells may represent a novel therapeutic method for patients with degenerative disc disease. METHODS: Adenoviral delivery vectors expressing Sox9 and green fluorescent protein were constructed using the AdEasy system. The chondroblastic cell line, HTB-94, and cultured human degenerated intervertebral disc cells were infected with the vectors. Reverse transcriptase-polymerase chain reaction and immunohistochemical analyses were performed to document increased Type 2 collagen expression. The AdSox9 virus then was injected directly into the intervertebral discs of three rabbits. After 5 weeks, the injected discs were evaluated histologically. RESULTS: The AdSox9 virus efficiently transduced HTB-94 cells and degenerated human disc cells. Western blot analysis confirmed increased Sox9 production. Increased Type 2 collagen production was demonstrated in infected HTB-94 and human disc cells using both reverse transcriptase-polymerase chain reaction and immunohistochemical staining. In the rabbit model, cells infected with AdSox9 maintained a chondrocytic phenotype, and the architecture of the nucleus pulposus was preserved over a 5-week study period compared to control discs. CONCLUSIONS:A novel adenoviral vector efficiently increased Sox9 and Type 2 collagen synthesis in cultured chondroblastic cells and human degenerated disc cells. In a rabbit model, sustained Sox9 production preserved the histologic appearance of the nucleus pulposus cells in vivo. These findings suggest a potential role for Sox9 gene therapy in the treatment of human degenerative disc disease.
机译：研究设计：在软骨细胞系和原代人椎间盘细胞中对表达Sox9（软骨细胞特异性转录因子）的新型重组腺病毒载体进行了体外测试。然后在兔模型中评估椎间盘细胞的直接感染。目的：将可能表达Sox9的治疗性病毒载体递送至退化的人和兔椎间盘细胞，并评估Sox9表达对2型胶原蛋白产生的影响。背景数据总结：2型胶原蛋白（健康的髓核的重要组成部分）的浓度随着椎间盘退变而降低。最近的研究表明，Sox9上调2型胶原蛋白的产生。椎间盘细胞增加2型胶原蛋白产生的干预措施可能代表了退行性椎间盘疾病患者的一种新型治疗方法。方法：使用AdEasy系统构建表达Sox9和绿色荧光蛋白的腺病毒载体。用该载体感染软骨母细胞系HTB-94和培养的人变性椎间盘细胞。进行逆转录酶-聚合酶链反应和免疫组化分析，以证明2型胶原蛋白表达增加。然后将AdSox9病毒直接注射到三只兔子的椎间盘中。 5周后，对注射的椎间盘进行组织学评估。结果：AdSox9病毒有效转导了HTB-94细胞和退化的人盘细胞。蛋白质印迹分析证实Sox9产量增加。使用逆转录酶-聚合酶链反应和免疫组织化学染色均证实在感染的HTB-94和人椎间盘细胞中2型胶原蛋白产生增加。在兔模型中，感染了AdSox9的细胞保持了软骨表型，与对照盘相比，髓核的结构在5周的研究期内得以保留。结论：一种新型腺病毒载体能有效地提高培养的软骨细胞和人变性椎间盘细胞中Sox9和2型胶原的合成。在兔模型中，持续的Sox9产生保留了体内髓核细胞的组织学外观。这些发现表明Sox9基因治疗在人类退行性椎间盘疾病的治疗中的潜在作用。

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