Table_10_Mandibular Vertical Growth Deficiency After Botulinum-Induced Hypotrophy of Masticatory Closing Muscles in Juvenile Nonhuman Primates.docx

The purpose of this study was to investigate the relationship between masticatory muscular hypotrophy and mandibular growth in juvenile nonhuman primates (cynolmolgus monkeys, Macaca fasicularis). We hypothesized that botulinum toxin (BTX)-induced neuro-muscular junctional block and its resultant hypotrophy of masticatory muscles would produce mandibular growth disturbances in size and shape. Ten male cynomolgus monkeys were divided into three groups: group I (control; n = 3), group II (unilateral BTX; n = 4), and group III (bilateral BTX; n = 3). The unilateral or bilateral muscular hypotrophy of major masticatory closing muscles was induced by synchronous BTX application to masseter, medial pterygoid, and temporal muscle. Mandibular growth was tracked by linear, angular, area and volume measurements using three-dimensional (3D) computed tomography imaging before BTX treatment and after 3 and 6 months. After unilateral hypotrophy of masticatory muscles in group II, vertical growth deficiency was prominent on the BTX side, with compensatory overgrowth on the control side. The bilateral muscular hypotrophy in group III also showed smaller ramal height and width than that of control (group I) and control side (group II). Moreover, ramal sagittal angles (posterior tilt) increased on the BTX side of both groups II and III, but coronal angles (lateral tilt) did so on the BTX side of group II, resulting in asymmetry. The results confirmed our hypothesis that functional activity of masticatory closing muscles is closely related to mandibular growth in size and shape of juvenile nonhuman primates. In addition, the focused growth disturbances on the ramal height and posterior-lateral tilt suggested the possible role of masticatory closing muscles for ramal vertical and angular growth vector of the mandible.

本研究旨在探讨幼年非人灵长类动物（食蟹猴，Macaca fasicularis）的咀嚼肌萎缩与下颌骨生长之间的关联。我们提出假说：肉毒毒素（botulinum toxin, BTX）诱导的神经肌肉接头阻滞及其引发的咀嚼肌萎缩，会导致下颌骨在尺寸与形态上出现生长紊乱。本研究纳入10只雄性食蟹猴，将其分为3组：对照组（I组，n=3）、单侧BTX组（II组，n=4）以及双侧BTX组（III组，n=3）。通过向咬肌、翼内肌及颞肌同步注射BTX，诱导各组动物主要闭口咀嚼肌发生单侧或双侧萎缩。分别于BTX注射前、注射后3个月及6个月，采用三维计算机断层成像（3D computed tomography）进行线性、角度、面积及体积测量，以追踪下颌骨生长情况。II组单侧咀嚼肌萎缩后，BTX注射侧可见明显的垂直生长不足，对侧则出现代偿性过度生长。III组双侧咀嚼肌萎缩后，其下颌升支高度与宽度均显著低于对照组（I组）及II组的对侧对照侧。此外，II组与III组BTX注射侧的下颌升支矢状角（后倾角）均有所增大；而II组BTX注射侧的冠状角（侧倾角）亦出现增大，最终导致颌面部不对称。本研究结果证实了我们的假说：咀嚼闭口肌的功能活动与幼年非人灵长类动物下颌骨的尺寸及形态生长密切相关。此外，下颌升支高度与后外侧倾方向的特异性生长紊乱提示，咀嚼闭口肌可能参与调控下颌骨升支的垂直生长及角度生长矢量。