King G N, Hughes F J
Department of Periodontics, Dental School University of Texas, San Antonio 78229-3900, USA.
J Clin Periodontol. 2001 May;28(5):465-75. doi: 10.1034/j.1600-051x.2001.028005465.x.
The unique action of bone morphogenetic proteins (BMPs) on mineralised tissue formation indicates that BMPs are good candidates for use in stimulating periodontal regeneration. Relatively little is known about the mechanisms of actions of BMPs during periodontal regeneration, although recent evidence from our laboratory suggests that the effects of BMPs may be profoundly influenced by various factors including root surface conditioning, delivery systems and masticatory forces.
The aim of this study was to investigate the effect of rhBMP-2 on cell recruitment during periodontal regeneration using a pulse-chase technique where cells are labelled with a thymidine analogue (BrdU) (pulse) and the migration of their progeny is followed (chase) during early wound healing. The relationship between the rhBMP-2 influence on cell recruitment from the periodontal ligament (PDL) and its ability to stimulate cementogenesis was also evaluated.
The buccal aspect of the distal root of the first molar was denuded of its PDL, cementum and superficial dentine through a bony window created in the mandible of 64 Wistar rats under general anaesthesia. Test animals were treated with 10 microL of 500 microg/ml rhBMP-2 in a collagen membrane sponge (n=32) and control defects received 10 microl of saline in a collagen sponge (n=32). All animals received an intraperitoneal single pulse injection of 40 mg/kg BrdU label 2 days postoperatively. Groups of test and control animals (n=8) were killed 2 hours later on day 2 and at 4, 7 and 10 days postoperatively. Mandibles were processed for histological examination.
The results show that rhBMP-2 had a profound effect on proliferation and migration of cells in the adjacent and deeper aspects of the PDL at 7 and 10 days post periodontal wounding (p<0.05). Significantly greater new cementum formation occurred in the test group at 10 days (p=0.03).
This study shows that following periodontal wounding rhBMP-2 stimulates cell recruitment by increasing proliferation and migration of cells from the adjacent unwounded PDL into the wounded area, thus promoting periodontal regeneration by increasing new cementum formation.
骨形态发生蛋白（BMPs）对矿化组织形成具有独特作用，这表明BMPs是刺激牙周组织再生的良好候选物。尽管我们实验室最近的证据表明，BMPs的作用可能受到多种因素的深刻影响，包括根面处理、递送系统和咀嚼力，但关于BMPs在牙周组织再生过程中的作用机制仍知之甚少。
本研究旨在使用脉冲追踪技术，研究重组人骨形态发生蛋白-2（rhBMP-2）对牙周组织再生过程中细胞募集的影响，即在早期伤口愈合过程中，用胸苷类似物（BrdU）标记细胞（脉冲），然后追踪其后代的迁移情况（追踪）。同时评估rhBMP-2对牙周韧带（PDL）细胞募集的影响与其刺激牙骨质形成能力之间的关系。
在全身麻醉下，通过在64只Wistar大鼠下颌骨上创建的骨窗，去除第一磨牙远中根颊侧的牙周韧带、牙骨质和表层牙本质。将10μl浓度为500μg/ml的rhBMP-2置于胶原膜海绵中处理试验动物（n = 32），对照缺损在胶原海绵中注入10μl生理盐水（n = 32）。所有动物在术后第2天腹腔内单次注射40mg/kg BrdU标记物。术后第2天2小时以及术后第4、7和10天，处死试验组和对照组动物（n = 8）。对下颌骨进行组织学检查。
结果显示，在牙周创伤后7天和10天，rhBMP-2对PDL相邻及更深层的细胞增殖和迁移有显著影响（p < 0.05）。试验组在第10天有明显更多的新牙骨质形成（p = 0.03）。
本研究表明，牙周创伤后，rhBMP-2通过增加相邻未损伤PDL细胞的增殖和迁移，使其进入损伤区域，从而刺激细胞募集，进而通过增加新牙骨质形成促进牙周组织再生。
