Alternative treatments for disc degeneration: Effects on matrix homeostasis

描述（由申请人提供）：椎间盘退变的特征是椎间盘高度进行性下降，与含水量和蛋白聚糖的损失有关。参与这一过程的关键机制包括炎症和机械应力。从生物学的角度来看，瑜伽或营养补充剂等辅助治疗可能通过这些途径对脊柱发挥有益作用。本研究的基本目标是通过体外和体内系统研究运动疗法（如瑜伽）和口服补充剂（包括葡萄糖胺、软骨素和omega-3脂肪酸）对椎间盘基质平衡的影响机制。这项工作的直接影响是通过细胞培养和动物模型系统证明了机械负荷和营养补充剂对椎间盘的生物效应。这将为我们提供一个强大的实验平台，通过该平台我们可以测试各种附加加载范式以及营养补充剂对椎间盘基质稳态的影响。在阐明受影响的生化途径后，未来的研究将把模型系统与基于CAM运动的治疗相关的人类脊柱运动学联系起来。这将导致将这些发现转化为更多机械指导的临床研究和合理靶向治疗的能力，这代表了候选人的长期目标。这项工作和通过拟议的培训计划获得的专业知识将作为一个研究项目的初步基石，在这个研究项目中，CAM问题可以在分子、组织和整个生物体水平上得到解决。相关性（见说明）：在2004年CDC的一份报告中，腰痛被确定为患者寻求瑜伽和口服补充剂等替代治疗的最常见疾病。为了最有效地利用这些干预措施，了解这些治疗方法如何促进其效果至关重要。这项研究的目的是了解以运动为基础的疗法，如瑜伽和口服补充剂，包括葡萄糖胺、软骨素和omega-3脂肪酸，对脊柱软骨的影响。

DESCRIPTION (provided by applicant): Intervertebral disc degeneration is characterized by progressive loss of disc height related to loss of water content and proteoglycans. Key mechanisms involved in this process include inflammatory and mechanical stress. It is biologically plausible that CAM therapies, such as yoga or nutritional supplements, may exert their beneficial actions on the spine through these pathways. The fundamental goals of this research are to investigate the mechanisms behind the effects of motion based therapies, such as yoga, and oral supplements, including glusosamine, chondroitin, and omega-3 fatty acids, on matrix balance in the intervertebral disc through use of both in vitro and in vivo systems. The immediate impact of this work is in demonstrating the biologic effects of mechanical loading and nutritional supplements on the intervertebral disc using cell culture and animal model systems. This will provide us with a powerful experimental platform with which we can test the effect of various additional loading paradigms as well as nutritional supplements on disc matrix homeostasis. Upon elucidation of the effected biochemical pathways, future studies will correlate the model systems to human spine kinematics relevant to CAM motion based therapies. This will result in the ability to translate these findings into more mechanistically directed clinical studies and rationally targeted therapeutics, which represents the long term goal of the candidate. This work and the expertise gained through the proposed training plan will serve as initial building blocks for a research program in which CAM questions can be addressed at the molecular, tissue, and whole organism level. RELEVANCE (See instructions): In a CDC report from 2004, low back pain was identified as the most common condition for which patients sought alternative treatments such as yoga and oral supplements. To utilize these interventions most effectively, it is critical to understand how these therapies are facilitating their effects. The goals of this research are to understand the effects of motion based therapies, such as yoga, and oral supplements, including glusosamine, chondroitin, and omega-3 fatty acids, on the cartilage of the spine. PUBLIC HEALTH RELEVANCE: In a CDC report from 2004, low back pain was identified as the most common condition for which patients sought alternative treatments such as yoga and oral supplements. To utilize these interventions most effectively, it is critical to understand how these therapies are facilitating their effects. The goals of this research are to understand the effects of motion based therapies, such as yoga, and oral supplements, including glusosamine, chondroitin, and omega-3 fatty acids, on the cartilage of the spine.