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持续拉伸牵张对椎体和椎间盘生长的影响:一项使用小鼠尾巴模型的体内研究

Effects of Sustained Tensile Distraction on Vertebrae and Intervertebral Disc Growth: An in Vivo Study Using a Mouse Tail Model.

作者信息

Salari Pooria, Easson Garrett W D, Broz Kaitlyn S, Kelly Michael P, Tang Simon Y

机构信息

Department of Orthopedics at Washington University in St. Louis, St. Louis, Missouri.

Kaiser Permanente, Sacramento, California.

出版信息

J Bone Joint Surg Am. 2025 May 21;107(10):1107-1115. doi: 10.2106/JBJS.24.00224. Epub 2025 Apr 3.

DOI:10.2106/JBJS.24.00224
PMID:40179155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12080362/
Abstract

BACKGROUND

Directed growth modulation is commonly utilized as a surgical treatment for early-onset scoliosis. Growing rods are instrumented on the spine and apply sustained tension on the immature spine for a substantial amount of time, with the clinical goal of accommodating axial expansion of the spine. Despite the use of growing rods in humans, the mechanobiology of the spinal tissues under tensile loading remains relatively unknown. To bridge this knowledge gap, we developed a preclinical mouse model that allows for mechanistic investigations of sustained tension on the spine.

METHODS

Using custom 3D-printed washers and tunable springs, we distracted across the seventh and ninth caudal vertebrae of adolescent and young adult C57BL/6 female mice with forces that were approximately 2 times the body mass of the animal. The springs were replaced weekly to maintain tension for the duration of the experiment. A set of 6-week-old animals were first instrumented for 10 weeks to evaluate the feasibility and tolerability. Subsequently, the 6- and 12-week-old experimental animals were instrumented until they were 20 weeks of age in order to evaluate the effects of tension until adulthood. The spines were monitored using digital radiography and micro-computed tomography (µCT), and the intervertebral discs (IVDs) were evaluated using mechanical testing and compositional assays.

RESULTS

The device was well tolerated and caused no notable complications. The tensile forces lengthened the vertebrae in the 6-week-old animals that were instrumented for 14 weeks and in the 12-week-old animals that were instrumented for 8 weeks. Increased IVD heights were observed in the 6-week-old animals but not in the 12-week-old animals. The porosity of the vertebral end plates increased following instrumentation in all groups but progressively recovered over time.

CONCLUSIONS

Distraction accelerated the lengthening of the vertebrae and the heightening of the IVD, with no observable degeneration or decline in the mechanical performance of the IVDs for these distraction conditions.

CLINICAL RELEVANCE

This model will be useful for investigating how spinal tissues adapt to directed growth modulation with maturation and aging.

摘要

背景

定向生长调节通常被用作早发性脊柱侧弯的外科治疗方法。生长棒被植入脊柱,并在相当长的一段时间内对未成熟的脊柱施加持续的张力,临床目标是适应脊柱的轴向生长。尽管生长棒已应用于人体,但拉伸载荷下脊柱组织的力学生物学仍相对未知。为了填补这一知识空白,我们开发了一种临床前小鼠模型,用于对脊柱持续张力进行机制研究。

方法

我们使用定制的3D打印垫圈和可调弹簧,以约为动物体重2倍的力牵张青春期和年轻成年C57BL/6雌性小鼠的第七和第九尾椎。每周更换弹簧以在实验期间维持张力。一组6周龄的动物先植入装置10周以评估可行性和耐受性。随后,对6周龄和12周龄的实验动物进行植入,直至它们20周龄,以评估张力对成年期的影响。使用数字X射线摄影和微计算机断层扫描(µCT)监测脊柱,并使用力学测试和成分分析评估椎间盘(IVD)。

结果

该装置耐受性良好,未引起明显并发症。拉伸力使植入14周的6周龄动物和植入8周的12周龄动物的椎骨延长。在6周龄动物中观察到IVD高度增加,但在12周龄动物中未观察到。所有组在植入后椎骨终板的孔隙率增加,但随时间逐渐恢复。

结论

牵张加速了椎骨的延长和IVD的增高,在这些牵张条件下,IVD没有明显的退变或力学性能下降。

临床意义

该模型将有助于研究脊柱组织如何随着成熟和衰老适应定向生长调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/e6a978ac1f28/jbjsam-107-1107-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/d3cf1f0778cb/jbjsam-107-1107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/6d196bae469e/jbjsam-107-1107-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/9ef6c18037e3/jbjsam-107-1107-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/e6a978ac1f28/jbjsam-107-1107-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/d3cf1f0778cb/jbjsam-107-1107-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/6d196bae469e/jbjsam-107-1107-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/7e5f99844dbd/jbjsam-107-1107-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/9ef6c18037e3/jbjsam-107-1107-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/12080362/e6a978ac1f28/jbjsam-107-1107-g005.jpg

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Autofusion in early-onset scoliosis growing constructs: occurrence, risk factors, and impacts.早发性脊柱侧凸生长矫形器中的自动融合:发生率、危险因素和影响。
Spine Deform. 2024 Jul;12(4):1155-1163. doi: 10.1007/s43390-024-00853-8. Epub 2024 Apr 4.
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TRPV4 differentially controls inflammatory cytokine networks during static and dynamic compression of the intervertebral disc.
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JOR Spine. 2023 Oct 27;6(4):e1282. doi: 10.1002/jsp2.1282. eCollection 2023 Dec.
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Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc.TRPV4 的调节可防止持续负荷引起的退变,并促进椎间盘基质合成。
FASEB J. 2023 Feb;37(2):e22714. doi: 10.1096/fj.202201388R.
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Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to the mouse lumbar intervertebral disc.对比增强微 CT 评价小鼠腰椎间盘部分和全宽损伤后的退变。
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