An in vivo model of ligamentum flavum hypertrophy from early-stage inflammation to fibrosis.

An in vivo model of ligamentum flavum hypertrophy from early-stage inflammation to fibrosis.
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DOI:
10.1002/jsp2.1260
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发表时间:
2023-09
期刊:
影响因子:
3.7
通讯作者:
Chahine, Nadeen O.
Chahine, Nadeen O.
中科院分区:
医学3区
文献类型:
--
作者:
Burt, Kevin G.;Viola, Dan C.;Lisiewski, Lauren E.;Lombardi, Joseph M.;Amorosa, Louis F.;Chahine, Nadeen O.

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腰椎中的多关节疾病病理,包括黄韧带(LF)肥大和椎间盘(IVD)膨出或突出导致腰椎管狭窄(LSS),这是一种以症状性椎管狭窄为特征的高度流行疾病。临床肥大性LF的特征在于弹性纤维的损失和胶原纤维的增加,导致纤维化增厚和瘢痕形成。在这项研究中,我们建立了一个损伤模型,以测试的假设,LF针刮伤在大鼠将导致肥大的LF改变组织的几何形状,基质组织,组成和炎症。进行了初步初步研究,以评价针头尺寸的影响。结果表明,使用22 G针的LF针刮伤在损伤后1周产生促炎细胞因子IL 6的上调,在损伤后8周增加Ctgf和Tgfb 1的表达,沿着在损伤后1、3和8周持续存在浸润性巨噬细胞。LF的完整性也发生了改变,表现为损伤后8周LF组织厚度增加和弹性组织丧失。持续性LF损伤还在腰椎IVD中产生多关节效应,包括损伤节段和邻近损伤节段的椎间盘高度损失,在邻近节段观察到退行性IVD变化。这些结果表明,LF刮伤在大鼠产生LF肥大和IVD高度和组织学变化的结构和分子特征,依赖于水平。该模型可用于检测与LF肥大相关的LSS和IVD变性的治疗干预。本研究表明,黄韧带(LF)在大鼠腰椎损伤产生炎症激活和LF肥大的功能。还观察到LF损伤后腰椎间盘的多关节变化。结果表明,在体内模型中,LF损伤导致LF肥大的结构和分子特征以及椎间盘高度和组织学变化,取决于水平。
Multi‐joint disease pathologies in the lumbar spine, including ligamentum flavum (LF) hypertrophy and intervertebral disc (IVD) bulging or herniation contribute to lumbar spinal stenosis (LSS), a highly prevalent condition characterized by symptomatic narrowing of the spinal canal. Clinical hypertrophic LF is characterized by a loss of elastic fibers and increase in collagen fibers, resulting in fibrotic thickening and scar formation. In this study, we created an injury model to test the hypothesis that LF needle scrape injury in the rat will result in hypertrophy of the LF characterized by altered tissue geometry, matrix organization, composition and inflammation. An initial pilot study was conducted to evaluate effect of needle size. Results indicate that LF needle scrape injury using a 22G needle produced upregulation of the pro‐inflammatory cytokine Il6 at 1 week post injury, and increased expression of Ctgf and Tgfb1 at 8 weeks post injury, along with persistent presence of infiltrating macrophages at 1, 3, and 8 weeks post injury. LF integrity was also altered, evidenced by increases in LF tissue thickness and loss of elastic tissue by 8 weeks post injury. Persistent LF injury also produced multi‐joint effects in the lumbar IVD, including disc height loss at the injury and adjacent to injury level, with degenerative IVD changes observed in the adjacent level. These results demonstrate that LF scrape injury in the rat produces structural and molecular features of LF hypertrophy and IVD height and histological changes, dependent on level. This model may be useful for testing of therapeutic interventions for treatment of LSS and IVD degeneration associated with LF hypertrophy. This study shows that ligamentum flavum (LF) injury in the rat lumbar spine produces features of inflammatory activation and LF hypertrophy. Multi‐joint changes in the lumbar intervertebral disc were also observed in response to LF injury. Results demonstrate that LF injury results in structural and molecular features of LF hypertrophy and intervertebral disc height and histological changes, dependent on level, in an in vivo model.
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