Endplate permeability and spinal disc degeneration

终板通透性和椎间盘退变

• 批准号: 7864146
• 负责人: JEFFREY C. LOTZ
• 金额: $ 31.93万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7864146
• 关键词: Adult; Affect; Age; Analysis of Variance; Architecture; Back Pain; Binding Sites; Biochemical; Biochemistry; Biomechanics; Blood Vessels; Blood capillaries; Bone remodeling; Caliber; Cartilage; Cell Count; Cell Death; Cell Density; Cell Nucleus; Cell Survival; Cell Transplantation; Cells; Cellularity; Characteristics; Chondroitin Sulfates; Collagen; Data; Dextrans; Diffusion; Equation; Etiology; Event; Fatigue; Filtration; Fluorescein; Fluoresceins; Fluorescence; Functional disorder; Future; Gender; Genes; Goals; Growth Factor; Harvest; Health; Height; Histology; Human; Human body; Hyaline Cartilage; Hyaluronan; Hydration status; Image; Intervertebral disc structure; Keratan Sulfate; Label; Length; Light; Liquid substance; MRI Scans; Magnetic Resonance Imaging; Malnutrition; Measures; Mechanics; Membrane; Metabolism; Modeling; Modification; Molecular Weight; Morphology; Nuclear; Nutrient; Pain; Pathologic Processes; Pathology; Patients; Permeability; Ploidies; Porosity; Precipitating Factors; Procedures; Process; Property; Proteoglycan; Relative (related person); Research Personnel; Role; Sampling; Secondary to; Signal Transduction; Solutions; Source; Specimen; Spectroscopy, Fourier Transform Infrared; Spinal; Staging; Structure; Swelling; Techniques; Testing; Time; Tissue Engineering; Tissues; To specify; Variant; Vertebral column; Water; age related; articular cartilage; base; bone; capillary; dextran; disability; disc regeneration; fluorophore; interest; intervertebral disk degeneration; nucleus pulposus; nutrition; physical property; pressure; programs; repaired; solute; spine bone structure; theories; vertebra body

DESCRIPTION (provided by applicant): Intervertebral disc degeneration is a significant source of pain and disability among US adults. While the etiology is varied and unknown in many patients, there is growing evidence that poor disc nutrition is an important precipitating factor. This is because the disc is the largest avascular tissue in the human body, and disc cell nutrition is critically dependent on diffusion from nearby tissues. Among the disc sub-tissues, the nucleus pulposus is the farthest from its nutrient supply (approximately 5 mm from capillaries in adjacent vertebra), and its dysfunction is implicated as an early common event in the overall degeneration cascade. The vertebral endplate is a hyaline cartilage layer that separates the nucleus from vertebral capillaries, and current theories state that decreasing endplate permeability (due to hypermineralization) causes decreasing nucleus cellularity and degradation in nuclear physical properties. Yet, there are no quantitative data that define how endplate permeability changes with age, degeneration, or spinal level. There is growing interest in tissue engineering approaches for disc repair that include rebuilding the nucleus pulposus by augmenting disc cell numbers (via cell transplantation) and signaling these cells to secrete vital matrix components (via gene or growth factor therapy). However, for this tactic to be successful, nutrient transport must keep up with the demands of increased cell numbers and metabolism. Yet, by definition this cannot happen if poor nutrition initiated degeneration in the first place. The goal of this proposal is to harvest endplates from 180 human discs, measure their permeability, and relate this to specimen specific variables that include subchondral bone porosity and hyaline cartilage biochemistry and structure. Endplate permeability will also be related to nucleus cellularity and overall disc degeneration to test the hypothesis that poor disc nutrition via decreased endplate permeability is an important etiologic factor for disc degeneration. We will also define the nucleus cellularity and endplate permeability compatible with healthy disc architecture. These data will be important to clarify the role of compromised nutrition in disc degeneration, and to specify whether endplate permeability modification is necessary to augment successful tissue engineering approaches for disc repair.

描述（由申请人提供）：椎间盘退变是美国成年人疼痛和残疾的重要来源。虽然病因是多种多样的，在许多患者中是未知的，但越来越多的证据表明，椎间盘营养不良是一个重要的诱发因素。这是因为椎间盘是人体内最大的无血管组织，椎间盘细胞营养严重依赖于附近组织的扩散。在椎间盘亚组织中，髓核距离其营养供应最远（距离相邻椎骨中的毛细血管约5 mm），并且其功能障碍被认为是整体退变级联中的早期常见事件。椎体终板是将细胞核与椎体毛细血管分开的透明软骨层，目前的理论认为，终板渗透性降低（由于过度矿化）会导致细胞核细胞数减少和细胞核物理性质退化。然而，没有定量数据来定义终板渗透性如何随年龄、退变或脊柱水平而变化。人们对椎间盘修复的组织工程方法越来越感兴趣，包括通过增加椎间盘细胞数量（通过细胞移植）重建髓核，并向这些细胞发出信号以分泌重要的基质成分（通过基因或生长因子治疗）。然而，为了使这种策略成功，营养运输必须跟上增加的细胞数量和新陈代谢的需求。然而，根据定义，如果营养不良首先导致退化，这种情况就不会发生。本提案的目标是从180个人类椎间盘中收获终板，测量其渗透性，并将其与标本特定变量（包括软骨下骨孔隙度和透明软骨生物化学和结构）相关。终板渗透性也将与核细胞构成和整体椎间盘退变相关，以检验终板渗透性降低导致的椎间盘营养不良是椎间盘退变的重要病因这一假设。我们还将确定与健康椎间盘结构相容的核细胞结构和终板渗透性。这些数据对于阐明营养不良在椎间盘退变中的作用，以及明确终板渗透性改变是否是成功的椎间盘修复组织工程方法所必需的将是重要的。

项目成果

Innervation patterns of PGP 9.5-positive nerve fibers within the human lumbar vertebra.

PGP 9.5阳性神经纤维的神经纤维神经模式。

• DOI: 10.1111/j.1469-7580.2010.01332.x
• 发表时间: 2011-03
• 期刊: Journal of anatomy
• 影响因子: 2.4
• 作者: Bailey JF;Liebenberg E;Degmetich S;Lotz JC
• 通讯作者: Lotz JC

Disk degeneration and low back pain: are they fat-related conditions?

• DOI: 10.1055/s-0033-1350054
• 发表时间: 2013-06
• 期刊: Global spine journal
• 影响因子: 2.4
• 作者: Samartzis D;Karppinen J;Cheung JP;Lotz J
• 通讯作者: Lotz J

The role of the vertebral end plate in low back pain.

• DOI: 10.1055/s-0033-1347298
• 发表时间: 2013-06
• 期刊: Global spine journal
• 影响因子: 2.4
• 作者: Lotz JC;Fields AJ;Liebenberg EC
• 通讯作者: Liebenberg EC

Morphology of the human vertebral endplate.

• DOI: 10.1002/jor.21513
• 发表时间: 2012-02
• 期刊: JOURNAL OF ORTHOPAEDIC RESEARCH
• 影响因子: 2.8
• 作者: Rodriguez, Azucena G.;Rodriguez-Soto, Ana E.;Burghardt, Andrew J.;Berven, Sigurd;Majumdar, Sharmila;Lotz, Jeffrey C.
• 通讯作者: Lotz, Jeffrey C.

Innervation of pathologies in the lumbar vertebral end plate and intervertebral disc.

腰椎端板和椎间盘的病理神经。

• DOI: 10.1016/j.spinee.2013.06.075
• 发表时间: 2014-03-01
• 期刊: SPINE JOURNAL
• 影响因子: 4.5
• 作者: Fields, Aaron J.;Liebenberg, Ellen C.;Lotz, Jeffrey C.
• 通讯作者: Lotz, Jeffrey C.