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: 10252759
• 负责人: Rebecca Chung
• 金额: $ 1.49万
• 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 2021-05-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252759
• 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.

项目摘要/摘要 哺乳和更年期是物理事件 代谢是由雌激素快速下降的共享内分泌信号触发的，导致骨质流失。 因此，腰痛，尤其是在生育和更年期期间，通常是相关的 椎间盘变性（IVDD）和椎骨骨质疏松症。临床研究 提出，均等对自我报告的LBP没有或负面影响，而最近的一项病例对照研究报告了 母乳喂养是基本女性临床诊断IVDD的保护因素。结果，存在一个 关于繁殖和泌乳对FSU的影响的批判知识差距，独立于FSU 育儿的非生物影响。由于功能性脊柱单元（FSU）由椎骨（VB）组成， 软骨端板（CEP）和椎间盘（IVD），了解繁殖的互动效应 在CEP和IVD稳态上的更年期对于发现FSU的可能机制至关重要 更改以适应苛刻的代谢条件。 我们的研究小组以前已经报道了怀孕期间明显的椎骨骨质流失和 哺乳后，断奶后快速恢复。此外，泌乳历史行使受保护的效果 在VB上针对绝经后骨质疏松症。尤其是围层 - 核酸（PLC）重塑活动 在生殖历史的大鼠中显着增加了ovx，这可能会导致增加 在lacunar-analicular系统内的可溶性运输，随后的营养递送改变和 VB和CEP之间的运输可能会影响IVD健康。因此，我们假设一个类似的先天 繁殖的补偿机制可以通过增强来预防绝经后IVDD PLC重塑增加而导致的FSU内局部营养递送和运输。 该提案的目的是建立和监视椎间盘的变化 FSU响应雌激素缺乏症的变性，并确定可能的机制 可能会区分有或没有繁殖史的大鼠的反应。我们将（1）建立一个 动物模型确定生殖和泌乳对IVD组织的生物学作用，并建立 通过研究其对IVD健康的互动影响，繁殖与更年期之间的直接联系； （2）专注于骨骼和CEP界面处的局部可溶性运输； （3）揭示骨细胞的新功能 PLC重塑跨IVD-CEP-VB功能单元调节营养转运； （4）开发和利用 成像模态（体内µCT和定量MRI T1和T2映射）以跟踪结构变化 IVD-CEP-VB功能单元和IVD的固体难度。阐明 FSU的再现和泌乳将提供有关是否需要采取预防措施的临床见解 通过考虑繁殖和泌乳的地位和史，被带到绝经后妇女。