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腰椎管狭窄症中肥厚的黄韧带与富含半胱氨酸的酸性分泌蛋白表达增加有关。

Hypertrophic Ligamentum Flavum in Lumbar Spine Stenosis Is Associated With the Increased Expression of Secreted Protein Acidic and Rich in Cysteine.

作者信息

Lee Ching-Yu, Wu Meng-Huang, Huang Tsung-Jen, Wang Po-Yao, Wu Alexander T H

机构信息

Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan.

Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

出版信息

Global Spine J. 2024 May;14(4):1248-1256. doi: 10.1177/21925682221138766. Epub 2022 Nov 10.

DOI:10.1177/21925682221138766
PMID:36355427
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11289542/
Abstract

STUDY DESIGN

Basic research.

OBJECTIVES

Secreted protein acidic and rich in cysteine (SPARC) is a critical pro-fibrotic mediator. This study aims to characterize the role of SPARC in hypertrophic ligamentum flavum (LF) and fibrosis.

METHODS

Hypertrophic LF samples were obtained from 8 patients with L4/5 lumbar spinal stenosis (LSS) during the decompressive laminectomy. Non-hypertrophic LF from age- and sex-matched 8 patients with L4/5 lumbar disc herniation was selected as control. An in vitro model of fibrosis in human LF cells was established by interleukin 6 (IL-6) to assess SPARC expression.

RESULTS

Hypertrophic LF samples had higher fibrosis scores than control samples by Masson's trichrome staining (3.6 vs. 1.3, < .001). Hypertrophic LF samples had significantly more positive staining for collagen and SPARC. Collagen III (Col3), α smooth muscle actin (α-SMA), and SPARC mRNA expression levels were significantly higher in hypertrophic LF samples than in control samples by qPCR. SPARC expression and fibrotic and inflammatory makers (collagen I, Col3, IL-6, interleukin 1β) were significantly upregulated in IL-6 stimulation of normal LF in vitro.

CONCLUSION

SPARC was detected in human LF and significantly upregulated in the clinical samples of hypertrophic LF compared to their normal counterparts. We also demonstrated an increased level of SPARC in an in vitro fibrosis model of LF. Thus, SPARC could be a crucial biomarker for the pathogenesis of hypertrophic LF and a therapeutic target for LSS.

摘要

研究设计

基础研究。

目的

富含半胱氨酸的酸性分泌蛋白（SPARC）是一种关键的促纤维化介质。本研究旨在阐明SPARC在肥厚性黄韧带（LF）及纤维化中的作用。

方法

在减压性椎板切除术中从8例L4/5腰椎管狭窄症（LSS）患者获取肥厚性LF样本。选取8例年龄和性别匹配的L4/5腰椎间盘突出症患者的非肥厚性LF作为对照。通过白细胞介素6（IL-6）建立人LF细胞纤维化的体外模型，以评估SPARC表达。

结果

通过Masson三色染色法，肥厚性LF样本的纤维化评分高于对照样本（3.6对1.3，<0.001）。肥厚性LF样本中胶原蛋白和SPARC的阳性染色明显更多。通过定量聚合酶链反应（qPCR），肥厚性LF样本中III型胶原蛋白（Col3）、α平滑肌肌动蛋白（α-SMA）和SPARC信使核糖核酸（mRNA）表达水平显著高于对照样本。在体外IL-6刺激正常LF时，SPARC表达以及纤维化和炎症标志物（I型胶原蛋白、Col3、IL-6、白细胞介素1β）显著上调。

结论

在人LF中检测到SPARC，与正常对应物相比，其在肥厚性LF临床样本中显著上调。我们还在LF的体外纤维化模型中证明了SPARC水平升高。因此，SPARC可能是肥厚性LF发病机制的关键生物标志物以及LSS的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/3a8282318b32/10.1177_21925682221138766-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/e410379af29d/10.1177_21925682221138766-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/eb0a0c559011/10.1177_21925682221138766-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/924bd4810711/10.1177_21925682221138766-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/357655513c20/10.1177_21925682221138766-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/0f003adc3ce8/10.1177_21925682221138766-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/3a8282318b32/10.1177_21925682221138766-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/e410379af29d/10.1177_21925682221138766-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/eb0a0c559011/10.1177_21925682221138766-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/924bd4810711/10.1177_21925682221138766-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/357655513c20/10.1177_21925682221138766-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/0f003adc3ce8/10.1177_21925682221138766-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/478a/11289542/3a8282318b32/10.1177_21925682221138766-fig6.jpg

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本文引用的文献

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Sci Transl Med. 2021 Feb 24;13(582). doi: 10.1126/scitranslmed.abe5738.
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Macrophage Infiltration Is a Causative Factor for Ligamentum Flavum Hypertrophy through the Activation of Collagen Production in Fibroblasts.巨噬细胞浸润是通过激活成纤维细胞中胶原蛋白的产生而导致黄韧带肥厚的一个致病因素。
Am J Pathol. 2017 Dec;187(12):2831-2840. doi: 10.1016/j.ajpath.2017.08.020. Epub 2017 Sep 19.
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Myofibroblast in the ligamentum flavum hypertrophic activity.
黄韧带中的肌成纤维细胞肥大活性。
Eur Spine J. 2017 Aug;26(8):2021-2030. doi: 10.1007/s00586-017-4981-2. Epub 2017 Feb 8.
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The paradoxical relationship between ligamentum flavum hypertrophy and developmental lumbar spinal stenosis.黄韧带肥厚与发育性腰椎管狭窄之间的矛盾关系。
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Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing.细胞外基质蛋白 Sparc 在肌腱成熟和老化中的多效作用。
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Hypertrophy of ligamentum flavum in lumbar spine stenosis is associated with increased miR-155 level.腰椎管狭窄症中黄韧带肥厚与 miR-155 水平升高有关。
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