SPINAL CORD INJURY INDUCED OSTEOPOR0SIS

脊髓损伤引起的骨质疏松症

• 批准号: 3161748
• 负责人: VICKY HOLETS WHITTEMORE
• 金额: $ 17.97万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3161748
• 关键词: atomic absorption spectrometry; autoradiography; bone density; bone metabolism; calcification; calcitonin gene related peptide; calcium disorder; central nervous system; colorimetry; densitometry; enzyme linked immunosorbent assay; high performance liquid chromatography; histochemistry /cytochemistry; immunofluorescence technique; innervation; interleukin 1; laboratory rat; longitudinal animal study; medical complication; neuropeptide Y; neuropeptide receptor; neurotransmitter receptor; neurotransmitters; norepinephrine; northern blottings; osteoporosis; periosteums; radioimmunoassay; receptor binding; spinal cord injury; spinal cord surgery; spinal nerves; substance P; vasoactive intestinal peptide

The objective of the proposed research is to discover the neural mechanism(s) involved in osteoporosis following spinal cord injury. The results of these studies may be useful in understanding the mechanisms in osteoporosis of other etiologies (e.g., immobilization, post-menopausal osteoporosis, etc.). This research, using an animal model of spinal cord injury with some characteristics common to many spinal cord injured patients, represents a feasible way of investigating the causes of osteoporosis and for later developing possible treatments to prevent or replace this bone loss. The proposed research will determine if there are changes in neuropeptides, neurotransmitters and cytokines in nerves supplying bone and in their receptors on bone cells. Since both the central and peripheral nervous systems are altered after spinal trauma, we hypothesize that changes in these substances in nerves are involved in the osteoporosis which develops following spinal cord injury. This hypothesis can not be fully tested until we have fully characterized the osteoporosis and changes in neural factors after injury in this animal model. Therefore, the specific aims of this proposal are to: l. Define the alterations in bone metabolism and structure that occur following spinal cord injury (Phase 1); 2. Determine what, if any, changes in neural factors in nerve fibers supplying bone and periosteum occur following spinal cord injury (Phase 11); 3. Determine what, if any, changes in receptors for these neural factors occur in osteogenic tissue (Phase III); 4. Correlate the changes in neural factors and their receptors with changes in bone metabolism over time. Histomorphometry, mechanical testing, radioimmunoassays and molecular biology will be used to characterize bone loss over time following spinal cord injury (Phase I). In Phase II we will use immunohistochemistry, radioimmunoassays and molecular biology to determine changes in neuropeptide and catecholamine distribution and levels in bone and periosteum over time following spinal cord injury. Specifically, we will focus on two sensory neuropeptides [calcitonin gene-related peptide and substance P], two sympathetic neuropeptides [vasoactive intestinal polypeptide and neuropeptide Y), norepinephrine, and the cytokine interleukin-1. These substances are known to be contained in nerve fibers in bone and have been implicated as modulators of bone metabolism in vitro. Immunohistochemistry, homogenate receptor binding assays, and autoradiographic methods will be used to evaluate receptor changes (Phase III). The correlation of bone and nerve changes following spinal cord injury will provide a clearer understanding of the mechanisms underlying the development of osteoporosis following spinal cord injury. It will also provide a basis for future studies on the effects of specific neural factors on the development of osteoporosis using other in vivo techniques (e.g immunoneutralization and infusion.)

本研究的目的是发现神经元 脊髓损伤后骨质疏松症的机制。 这 这些研究的结果可能有助于理解其中的机制 其他病因引起的骨质疏松症（例如，不活动、绝经后 骨质疏松症等）。这项研究使用脊髓动物模型 损伤具有许多脊髓损伤所共有的一些特征 患者，代表了调查原因的可行方法 骨质疏松症以及以后开发可能的治疗方法来预防或 替代这种骨质流失。 拟议的研究将确定神经肽是否发生变化， 供应骨骼的神经及其骨骼中的神经递质和细胞因子 骨细胞上的受体。 由于中枢神经和周围神经 脊柱创伤后系统发生改变，我们假设 神经中的这些物质与骨质疏松症的发生有关 脊髓损伤后。 该假设无法得到充分检验 直到我们完全了解骨质疏松症和神经变化的特征 该动物模型中受伤后的因素。 因此，本提案的具体目标是： 湖定义骨代谢和结构发生的变化 脊髓损伤后（第一阶段）； 2. 确定神经纤维中神经因子的变化（如果有） 脊髓损伤后发生骨和骨膜的供应（阶段 11）； 3. 确定这些神经因子的受体发生了什么变化（如果有） 发生在成骨组织中（III期）； 4. 将神经因子及其受体的变化与变化联系起来 随着时间的推移骨代谢。 组织形态计量学、机械测试、放射免疫分析和分子 生物学将用于表征脊柱后随时间推移的骨质流失 脊髓损伤（第一阶段）。 在第二阶段我们将使用免疫组织化学， 放射免疫分析和分子生物学来确定变化 神经肽和儿茶酚胺在骨和骨中的分布和水平 脊髓损伤后骨膜随时间的推移。 具体来说，我们将 重点关注两种感觉神经肽【降钙素基因相关肽和 P物质]，两种交感神经肽[血管活性肠 多肽和神经肽 Y)、去甲肾上腺素和细胞因子 白细胞介素-1。 已知这些物质包含在神经纤维中 存在于骨骼中，并被认为是体外骨代谢的调节剂。 免疫组织化学、匀浆受体结合测定，以及 放射自显影方法将用于评估受体变化（阶段 三）。 脊髓后骨与神经变化的相关性 损伤将使人们更清楚地了解潜在的机制 脊髓损伤后骨质疏松症的发展。 它还将 为未来研究特定神经元的影响提供基础 使用其他体内技术影响骨质疏松症发展的因素 （例如免疫中和和输注。）