Yates K E, Troulis M J, Kaban L B, Glowacki J
Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Boston, USA.
Int J Oral Maxillofac Surg. 2002 Apr;31(2):173-8. doi: 10.1054/ijom.2001.0204.
The mechanisms that regulate bone formation during distraction osteogenesis (DO) are not completely understood. Our hypothesis is that local cytokines that stimulate osteoblast activity are potential regulators of this process. The purpose of this study was to determine gene expression of insulin-like growth factor I (IGF-I), transforming growth factor-beta (TGF-beta), and bone morphogenetic protein 4 (BMP-4) in distracted wounds. A semiburied, rigid distraction device was placed across an osteotomy at the right mandibular angle in 9 Yucatan minipigs. Distraction was begun immediately at a rate of 1 mm/day. The animals were sacrificed after 4 and 7 days of distraction, and after 7 days of distraction plus 4 days of neutral fixation. Excised wound tissues were processed for histologic and gene expression analyses. Competitive reverse-transcription polymerase chain reaction (RT-PCR) assays were developed and validated for porcine genes. Histologic analysis showed membranous ossification within the DO wound. Gene expression of IGF-I, TGF-beta and BMP-4 was detected during distraction and neutral fixation. These results show that gene expression analyses can be performed in a large animal model of mandibular DO. As the pig mandible closely resembles that of the human in morphology and physiology, this is an important step toward characterization of the early molecular events in the DO wound.
牵张成骨（DO）过程中调节骨形成的机制尚未完全明确。我们的假说是，刺激成骨细胞活性的局部细胞因子是这一过程的潜在调节因子。本研究的目的是确定牵张伤口中胰岛素样生长因子I（IGF-I）、转化生长因子-β（TGF-β）和骨形态发生蛋白4（BMP-4）的基因表达。在9只尤卡坦小型猪的右下颌角截骨处放置一个半埋入式刚性牵张装置。牵张立即以每天1毫米的速度开始。在牵张4天和7天后，以及牵张7天加4天中立固定后处死动物。对切除的伤口组织进行组织学和基因表达分析。针对猪基因开发并验证了竞争性逆转录聚合酶链反应（RT-PCR）检测方法。组织学分析显示DO伤口内有膜内成骨。在牵张和中立固定期间检测到IGF-I、TGF-β和BMP-4的基因表达。这些结果表明，基因表达分析可在大型下颌DO动物模型中进行。由于猪下颌骨在形态和生理上与人的下颌骨非常相似，这是朝着表征DO伤口早期分子事件迈出的重要一步。
