Mechanobiology in CAM: Differential Effects of Amplitude

CAM 中的力学生物学：振幅的差异效应

• 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
• 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

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.

椎间盘和小块软骨的变性是造成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失衡而导致的。多个过程导致基质降解，包括增加炎症，分解代谢增加和抗代谢降低。脊柱中的机械负荷已显示可介导这些过程以加速变性或促进修复。生物反应的阈值随载荷持续时间，频率和幅度而变化。该项目旨在探讨6个自由度（DOF）运动中运动范围（ROM）对可行兔功能性脊柱单元（FSU）中炎症和分解代谢标记的影响。使用新型的前机械生物学系统，加上现有的基于机器人的脊柱测试系统，将在DOF中应用振幅，以反映用于互补和替代医学（CAM）基于脊椎治疗的疗法（如脊骨疗法动员和瑜伽）的载荷模式。具体而言，将轴向旋转与后侧翻译（模拟脊骨疗法动员载荷模式）和屈曲 - 扩展ROM（模拟瑜伽载荷模式）将有所不同，以阐明幅度对生物学介体的影响。 加载后的生物学结果将包括通过炎症，分解代谢和抗代谢基因的实时RT-PCR相对基因表达，蛋白质表达和通过免疫组织化学和抗代谢蛋白的免疫组织化学以及ELISA释放的细胞因子和基质的培养基浓度的免疫组织化学。基于经典动员范例，假设重复（1 Hz，5倍）复杂的低振幅负载（2.50/0-0.25mm）将减少炎症介体和复杂的高振幅负载（50/0.25-0.5mm）将通过使Matrix Boustostasis的平衡或增加cattibial cattibial cattibip ant的平衡来改善。在屈伸性扩展中，假设ROM增加将通过减少分解代谢或增加抗代谢结果来使基质稳态受益。对与基于CAM运动的疗法相关的机械负载模式对脊柱负荷组织的影响的机械理解将为临床策略和研究提供依据，旨在为特定患者组合理规定运动疗法。最终，CAM方法的机理表征的临床影响将通过合理组合CAM疗法或将CAM方法与常规护理相结合，从而增强当前治疗，以进行最佳的特定治疗。