Load-Driven Bone Lengthening

描述(由申请人提供)： 拟议项目的长期目标是了解负荷驱动的骨延长的机制。虽然牵引成骨是治疗肢体长度不一致患者的有效方法，但这种侵入性手术偶尔会产生过早愈合、延迟愈合和感染等问题。为了研究负荷驱动非侵入性治疗的可能性，我们将重点研究膝关节负荷一种形式的关节负荷模式。在这个R03项目中，我们解决了一组问题：(1)膝关节负荷是否促进了生长板中软骨细胞的增殖，并延长了股骨远端和胫骨近端的增殖带和肥大区？(2)延长效应是否依赖于年龄？(3)生长板内注射胰岛素生长因子-2(IGF-2)是否增强了负荷效应？我们假设：(A)在适当的载荷条件下，施加在膝关节上的侧向载荷，可以通过刺激生长板中软骨细胞的增殖来延长股骨和胫骨；(B)载荷驱动的骨延长术在年轻人中的效果比老年人更强；以及(C)在老年人中通过在生长板中注射IGF-1可以增强这种延长效果。为了验证上述假设，以C57BL/6小鼠后肢为模型系统，提出了三个具体的研究目标。《不同力学条件下负荷驱动的骨延长的评估》《不同年龄小鼠负荷效果的比较》在生长板中局部注射IGF-2，在有和没有膝关节负荷的情况下的效果。我们将使用定制的压电式机械加载器，并使用不同的成像方式进行骨组织形态计量学和基因表达分析。这项拟议的研究有望有助于开发一种非侵入性物理疗法来治疗肢体长度不一致的患者。项目简介目前，侵入性外科手术(牵张成骨)通常用于延长长骨。然而，这一过程存在一系列潜在的风险，如过早愈合、延迟愈合、骨感染、关节僵硬和新骨形成的骨折。拟议的R03项目将有助于研究非侵入性物理疗法治疗肢体长度不一致患者的可能性。

DESCRIPTION (provided by applicant): The long-term objective of the proposed project is to understand the mechanism of load-driven bone lengthening. Although distraction osteogenesis is effective to treat the patients with limb length discrepancy, this invasive procedure occasionally generates problems such as premature consolidation, delayed union, and infection. In order to investigate a possibility of load-driven non-invasive therapy, we will focus on knee loading a form of joint loading modalities. In this R03 project, we address a set of questions: (1) Does knee loading enhance proliferation of chondrocytes in the growth plate and lengthen the proliferative and hypertrophic zones in the distal femur and the proximal tibia? (2) Is the lengthening effect dependent on ages? (3) Does injection of insulin growth factor-2 (IGF-2) into the growth plate enhance the loading effects? We hypothesize: (a) Lateral loads, applied to the knee with appropriate loading conditions, can lengthen both the femur and the tibia through stimulating proliferation of chondrocytes in the growth plate; (b) Efficacy of load-driven bone lengthening is stronger in the youth than the elderly; and (c) The lengthening effect can be augmented in the elderly by injecting IGF-1 in the growth plate. In order to examine the above hypotheses, three specific aims are proposed using a hindlimb of C57BL/6 mice as a model system. " Evaluation of load-driven bone lengthening under varying mechanical conditions " Comparison of the loading effects among mice with varying ages " Effects of local administration of IGF-2 into the growth plate with and without knee loading. We will use a custom-made piezoelectric mechanical loader, and conduct bone histomorphometric and gene expression analyses using varying imaging modalities. The proposed study is expected to contribute to developing a non-invasive physical therapy for treatment of patients with limb length discrepancy. PROJECT NARRATIVE Currently the invasive surgical procedure (distraction osteogenesis) is commonly employed to lengthen long bones. However, this procedure presents a series of potential risks such as premature consolidation, delayed union, bone infection, joint stiffness, and fracture of newly formed bone. The proposed R03 project will contribute to examining a possibility of non-invasive physical therapy for treatment of patients with limb length discrepancy.