Effects of reproduction and lactation on the functional spinal unit post menopause

绝经后生殖和哺乳对功能性脊柱单位的影响

• 批准号: 9910829
• 负责人: Rebecca Chung
• 金额: $ 6.53万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-05 至 2023-03-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9910829
• 关键词: Address; Age; Animal Model; Biological; Breast Feeding; Cartilage; Case-Control Studies; Clinical; Development; Diagnosis; Diffuse; Elderly woman; Endocrine; Estrogens; Event; Female; Functional disorder; Health; Histologic; Histology; Homeostasis; Image; Intervertebral disc structure; Knowledge; Lactation; Lead; Length; Life; Low Back Pain; Magnetic Resonance Imaging; Mechanics; Menopause; Metabolic; Metabolism; Minerals; Modeling; Monitor; Motivation; Needles; Nutrient; Operative Surgical Procedures; Osteocytes; Osteoporosis; Ovariectomy; Patient Self-Report; Physiological; Postmenopausal Osteoporosis; Postmenopause; Pregnancy; Prevention; Preventive measure; Puncture procedure; Rattus; Recording of previous events; Recovery; Reporting; Reproduction; Reproductive History; Research; Risk; Role; STEM research; Scanning; Signal Transduction; Spinal; Structure; System; Testing; Tissues; Vertebral Bone; Vertebral column; Weaning; Woman; Work; bone; bone loss; child bearing; clinical Diagnosis; clinical investigation; clinically relevant; cohort; contrast enhanced; density; imaging modality; in vivo; in vivo monitoring; insight; intervertebral disk degeneration; mechanical properties; microCT; microscopic imaging; novel; nutrition; parity; protective effect; protective factors; reproductive; response; skeletal; solute; substantia spongiosa; trend

Project Summary/Abstract Lactation and menopause are physiological events where substantial changes in mineral and skeletal metabolism are triggered by a shared endocrine signal of rapid estrogen decline, resulting in bone loss. Consequently, low back pain, particularly during childbearing and post menopause is commonly associated with intervertebral disc degeneration (IVDD) and osteoporosis of vertebral bone. Clinical investigations suggested that no or negative effect of parity on self-reported LBP while a recent case-control study reported breastfeeding as a protective factor for clinically diagnosed IVDD in elderly women. As a result, there exists a critical knowledge gap regarding the effects of reproduction and lactation on the FSU that are independent of non-biological effects of parenthood. As the functional spinal unit (FSU) consists of vertebral bone (VB), cartilage end plate (CEP), and intervertebral disc (IVD), understanding the interactive effects of reproduction and menopause on CEP and IVD homeostasis is essential to uncover possible mechanisms of how the FSU changes to accommodate demanding metabolic conditions. Our research group has previously reported significant vertebral bone loss during pregnancy and lactation followed by a rapid recovery post-weaning. Moreover, a history of lactation exerts a protective effect on VB against post-menopausal osteoporosis. In particular, perilacunar-canalicular (PLC) remodeling activities are significantly increased in rats with reproductive history post-OVX, which would likely lead to increased solute transport within the lacunar-canalicular system, and the subsequent altered nutrition delivery and transport between VB and CEP may impact IVD health. Therefore, we hypothesize that a similar innate compensatory mechanism from reproduction may protect against post-menopausal IVDD by enhancing the local nutrient delivery and transport within the FSU resulting from increased PLC remodeling. The objective of this proposal is to establish and monitor changes of intervertebral disc degeneration in the FSU in response to estrogen deficiency and identify possible mechanisms that may differentiate responses in rats with and without a reproduction history. We will (1) establish an animal model to determine the biological effect of reproduction and lactation on IVD tissue and establish a direct connection between reproduction and menopause by investigating their interactive effects on IVD health; (2) Focus on local solute transport at the bone and CEP interface; (3) Reveal novel functions of the osteocyte PLC remodeling in modulating nutrient transport across IVD-CEP-VB functional unit; (4) Develop and utilize imaging modalities (in vivo µCT and quantitative MRI T1 and T2 mapping) to track the structural changes of IVD-CEP-VB functional unit and examine solute diffusivity of the IVD. Elucidating the biological effects of reproduction and lactation on the FSU will provide clinical insight on whether preventative measures need to be taken for postmenopausal women by considering their status and history of reproduction and lactation.

项目概要/摘要 哺乳期和更年期是生理事件，矿物质和骨骼发生显着变化 新陈代谢是由雌激素快速下降的共同内分泌信号触发的，导致骨质流失。 经测试，腰痛，特别是在生育期间和绝经后通常与腰痛有关 椎间盘退变（IVDD）和椎骨骨质疏松症的临床研究。 表明胎次对自我报告的腰痛没有影响或有负面影响，而最近的一项病例对照研究报告 母乳喂养是老年女性临床诊断的 IVDD 的保护因素。 关于生殖和哺乳对 FSU 的影响的关键知识差距，这些影响独立于 由于功能性脊柱单位 (FSU) 由椎骨 (VB) 组成， 软骨终板 (CEP) 和椎间盘 (IVD)，了解生殖的相互作用 更年期对 CEP 和 IVD 稳态的影响对于揭示 FSU 的可能机制至关重要 改变以适应苛刻的代谢条件。 我们的研究小组之前曾报告过怀孕期间和 哺乳期断奶后迅速恢复此外，哺乳史也具有保护作用。 VB 对抗绝经后骨质疏松症，特别是腔管周围 (PLC) 重塑活动。 在具有 OVX 后生殖史的大鼠中显着增加，这可能导致增加 腔隙-小管系统内的溶质运输，以及随后改变的营养输送和 VB 和 CEP 之间的运输可能会影响 IVD 健康，因此，我们追求类似的先天性。 生殖补偿机制可以通过增强 由于 PLC 重塑的增加，导致 FSU 内的局部营养物输送和运输。 该提案的目的是确定和监测椎间盘的变化 FSU 因雌激素缺乏而退化，并确定可能的机制 可以区分有和没有繁殖史的大鼠的反应。我们将 (1) 建立一个模型。 动物模型以确定生殖和哺乳对 IVD 组织的生物学影响并建立 通过调查生殖与更年期对 IVD 健康的相互作用影响，了解生殖与更年期之间的直接联系； (2) 关注骨与CEP界面的局部溶质转运； (3) 揭示骨细胞的新功能； PLC重构调节IVD-CEP-VB功能单元的营养物质运输（4）开发和利用； 成像模式（体内 µCT 和定量 MRI T1 和 T2 映射）来跟踪结构变化 IVD-CEP-VB 功能单元并检查 IVD 的溶质扩散性，阐明其生物学效应。 FSU 上的生殖和哺乳将为预防是否需要采取措施提供临床见解 对于绝经后妇女，应考虑她们的状况以及生殖和哺乳史。