Mechanobiology in CAM: Differential Effects of Amplitude

CAM 中的力学生物学：振幅的差异效应

基本信息

批准号：
8383666
负责人：
Robert Allen Hartman
金额：
$ 4.32万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8383666
关键词：
ADAMTS Accounting Affect American Anabolism Anterior Articular Range of Motion Back Back Pain Biological Biology Caring Cartilage Catabolism Cells Clinical Clinical Treatment Complementary and alternative medicine Complex Coupled Data Disease Environment Enzyme-Linked Immunosorbent Assay Equilibrium Extracellular Matrix Extracellular Matrix Degradation Facet joint structure Freedom Frequencies Gene Expression Gene Proteins Genes Goals Heterogeneity Homeostasis Immunohistochemistry In Situ Inflammation Inflammation Mediators Inflammatory Interleukin-1 Interleukin-6 Interstitial Collagenase Intervention Intervertebral disc structure Joints Kinetics Knowledge Low Back Pain Measures Mechanics Mediating Mediator of activation protein Modality Modeling Motion Movement Oryctolagus cuniculus Outcome PTGS2 gene Patients Pattern Physiological Process Proteins Relative (related person)Relaxation Research Research Proposals Reverse Transcriptase Polymerase Chain Reaction Robot Rotation Signal Transduction Simulate Spinal Spinal Manipulation Stimulus Stress Stromelysin 1 System Techniques Testing Time Tissue Inhibitor of Metalloproteinase-1 Tissues Translations Vertebral column Weight-Bearing state Yoga base chiropracty court cytokine experience flexibility improved in vivo inflammatory marker intervertebral disk degeneration novel protein expression repaired response transmission process

项目摘要

Degeneration of the intervertebral disc and facet cartilage are among the most common causes of back pain. Degradation of the extracellular matrix of these tissues results from an imbalance in matrix catabolism and anabolism. Multiple processes contribute to degradation of the matrix including increased inflammation, increased catabolism and decreased anti-catabolism. Mechanical loading in the spine has been shown to mediate these processes to accelerate degeneration or to promote repair; thresholds of biological response vary as a function of loading duration, frequency, and magnitude. This project aims to explore the effect of range-of- motion (ROM) in 6 degree-of-freedom (DOF) motion on inflammatory and catabolic markers in viable rabbit functional spinal units (FSUs). Using a novel ex-vivo mechanobiological system coupled with an existing robot-based spine testing system, amplitudes will be applied in DOF that reflect patterns of loading used in complementary and alternative medicine (CAM) motion- based therapies like chiropractic mobilization and yoga. Specifically, coupled axial rotation with posterior-anterior translation (simulating chiropractic mobilization loading patterns) and flexion- extension ROM (simulating yoga loading patterns) will be varied to elucidate the effect of amplitude on biological mediators. Biological outcomes following loading will include relative gene expression by real time RT-PCR of inflammatory, catabolic and anti-catabolic genes, protein expression and localization by immunohistochemistry of catabolic and anti-catabolic proteins, and media concentrations of released cytokines and matrix fragments by ELISA. Based on classical mobilization paradigms, it is hypothesized that repetitive (15 s at 1 Hz, 5x) complex low amplitude loading (2.50/0-0.25mm) will reduce inflammatory mediators and complex high amplitude loading (50/0.25-0.5mm) will improve the balance of matrix homeostasis by reducing catabolic or increasing anti-catabolic markers. In flexion-extension, it is hypothesized that increased ROM will similarly benefit matrix homeostasis by reducing catabolic or increasing anti-catabolic outcomes. A mechanistic understanding of the influence of mechanical loading patterns relevant to CAM motion-based therapies on load-bearing tissues in the spine will inform clinical strategies and studies that aim to rationally prescribe motion therapy for specific patient groups. Ultimately, th clinical impact of a mechanistic characterization of CAM approaches to back pain would allow for enhancement of current treatment by rational combinations of CAM therapies or integrating CAM approaches with conventional care for optimal, specific treatment.

椎间盘和小关节软骨的退变是背痛的最常见原因之一。这些组织的细胞外基质的降解是由于基质分解代谢和合成代谢的不平衡造成的。多种过程导致基质降解，包括炎症增加、分解代谢增加和抗分解代谢减少。脊柱中的机械负荷已被证明可以介导这些过程，从而加速退化或促进修复；生物反应的阈值随着负荷持续时间、频率和强度的变化而变化。该项目旨在探索 6 自由度 (DOF) 运动中的运动范围 (ROM) 对活兔功能性脊柱单位 (FSU) 中炎症和分解代谢标志物的影响。使用新颖的离体机械生物学系统与现有的基于机器人的脊柱测试系统相结合，将在自由度中应用振幅，以反映补充和替代医学（CAM）基于运动的疗法（如脊椎按摩疗法和瑜伽）中使用的负载模式。具体来说，将改变耦合轴向旋转与后前平移（模拟脊椎按摩疗法动员负载模式）和屈伸 ROM（模拟瑜伽负载模式），以阐明振幅对生物介质的影响。加载后的生物学结果包括通过实时 RT-PCR 检测炎症、分解代谢和抗分解代谢基因的相对基因表达，通过免疫组织化学检测分解代谢和抗分解代谢蛋白的蛋白质表达和定位，以及通过 ELISA 检测释放的细胞因子和基质片段的培养基浓度。基于经典动员范式，假设重复（1 Hz，5x 下 15 秒）复杂低振幅负载（2.50/0-0.25mm）将减少炎症介质，而复杂高振幅负载（50/0.25-0.5mm）将减少炎症介质。通过减少分解代谢或增加抗分解代谢标志物来改善基质稳态的平衡。在屈曲伸展过程中，假设增加的活动度同样会通过减少分解代谢或增加抗分解代谢结果而有利于基质稳态。从机械角度理解与 CAM 运动疗法相关的机械负荷模式对脊柱承重组织的影响，将为旨在为特定患者群体合理制定运动疗法的临床策略和研究提供信息。最终，CAM 方法对背痛的机制特征的临床影响将允许通过 CAM 疗法的合理组合或将 CAM 方法与传统护理相结合以实现最佳、具体的治疗来增强当前的治疗。