Load-Driven Bone Lengthening

负载驱动的骨延长

• 批准号: 7513232
• 负责人: Ping Zhang
• 金额: $ 7.55万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-04 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7513232
• 关键词: Address; Age; Arthritis; Biological Models; Bone Lengthening; Buffers; C57BL/6 Mouse; Child; Chondrocytes; Condition; Contralateral; Control Animal; Cumulative Trauma Disorders; Custom; Dependence; Devices; Distal; Distraction Osteogenesis; Elderly; Epiphysial cartilage; Evaluation; Femur; Fetal Growth; Fracture; Frequencies; Gene Expression; Growth; Growth Factor; Height; Hindlimb; Hip region structure; Image; Infection; Injection of therapeutic agent; Insulin; Insulin-Like Growth Factor I; Invasive; Joints; Knee; Label; Lateral; Leg; Length; Lifting; Limb structure; Low Back Pain; Mechanics; Medical; Modality; Mus; Operative Surgical Procedures; Osteogenesis; Osteomyelitis; Patients; Physical therapy; Polymerase Chain Reaction; Procedures; Pump; Reaction; Risk; Series; Shoes; Signal Pathway; Solutions; Symptoms; Tendinitis; Testing; Time; Variant; Week; Youth; age effect; age group; bone; bone quality; fluorexon; joint stiffness; long bone; response; tibia

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.

描述（由申请人提供）： 该项目的长期目标是了解负载驱动的骨延长的机制。虽然牵引成骨对于治疗肢体不等长的患者是有效的，但这种侵入性手术有时会产生过早固结、延迟愈合和感染等问题。为了研究负载驱动的非侵入性治疗的可能性，我们将重点关注膝关节负载的一种关节负载方式。在这个R03项目中，我们解决了一系列问题：（1）膝关节负重是否会增强生长板中软骨细胞的增殖并延长股骨远端和胫骨近端的增殖和肥大区？ (2) 延长效果是否取决于年龄？ (3) 将胰岛素生长因子-2 (IGF-2) 注射到生长板中是否会增强负荷效应？我们假设：（a）在适当的负载条件下施加到膝盖的横向负载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) 负载驱动骨延长的功效在年轻人中比老年人更强； (c) 通过在生长板中注射 IGF-1 可以增强老年人的延长效果。为了检验上述假设，使用 C57BL/6 小鼠后肢作为模型系统提出了三个具体目标。 “不同机械条件下负载驱动骨延长的评估”不同年龄小鼠的负载效果比较“在有和没有膝关节负载的情况下将IGF-2局部施用到生长板中的效果。我们将使用定制的压电机械负载器，并使用不同的成像方式进行骨组织形态测量和基因表达分析。这项研究预计将有助于开发一种非侵入性的非侵入性骨延长器。” 物理治疗用于治疗肢体长度不等的患者。项目叙述 目前，侵入性外科手术（牵引成骨）通常用于延长长骨。然而，该手术存在一系列潜在风险，例如过早固结、延迟愈合、骨感染、关节僵硬和新形成的骨骨折。拟议的 R03 项目将有助于检查非侵入性物理治疗的可能性 用于治疗肢体长度不等的患者的疗法。