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SPARC 基因敲除小鼠诱导的椎间盘退变的力学后果。

Mechanical Consequence of Induced Intervertebral Disc Degeneration in the SPARC-Null Mouse.

机构信息

Department of Kinesiology and Physical Education, Wilfrid Laurier University, 75 University Avenue W, Waterloo, ON N2 L 3C5, Canada.

Faculty of Dentistry, McGill University, 845 Sherbrooke Street West, Montréal, QC H3A 0G4, Canada.

出版信息

J Biomech Eng. 2021 Feb 1;143(2). doi: 10.1115/1.4047995.

Abstract

Intervertebral disc (IVD) degeneration is associated with low back pain (LBP) and accompanied by mechanical changes to the spine. Secreted protein acidic and rich in cysteine (SPARC) is a protein that contributes to the functioning and maintenance of the extracellular matrix. SPARC-null mice display accelerated IVD degeneration and pain-associated behaviors. This study examined if SPARC-null mice also display altered spine mechanics as compared to wild-type (WT) mice. Lumbar spines from SPARC-null (n = 36) and WT (n = 18) mice aged 14-25 months were subjected to cyclic axial tension and compression to determine neutral zone (NZ) length and stiffness. Three separate mechanical tests were completed for each spine to determine the effect of the number of IVDs tested in series (one versus two versus three IVDs). SPARC-null spine NZs were both stiffer (p < 0.001) and smaller in length (p < 0.001) than WT spines. There was an effect of the number of IVDs tested in series for NZ length but not NZ stiffness when collapsed across condition (SPARC-null and WT). Correlation analysis revealed a weak negative correlation (r = -0.24) between age and NZ length in SPARC-null mice and a weak positive correlation (r = 0.30) between age and NZ stiffness in WT mice. In conclusion, SPARC-null mice had stiffer and smaller NZs than WT mice, regardless of the number of IVDs in series being tested. The increased stiffness of these IVDs likely influences mobility at these spinal joints thereby potentially contributing to low back pain.

摘要

椎间盘(IVD)退变与下腰痛(LBP)相关,并伴有脊柱的机械变化。富含半胱氨酸的酸性分泌蛋白(SPARC)是一种有助于细胞外基质功能和维持的蛋白质。SPARC 基因敲除小鼠表现出加速的 IVD 退变和与疼痛相关的行为。本研究旨在探讨 SPARC 基因敲除小鼠的脊柱力学是否也与野生型(WT)小鼠不同。14-25 月龄的 SPARC 基因敲除(n=36)和 WT(n=18)小鼠的腰椎接受周期性轴向张力和压缩,以确定中立区(NZ)长度和刚度。对每个脊柱进行了三次独立的机械测试,以确定串联测试的 IVD 数量的影响(一个、两个或三个 IVD)。与 WT 脊柱相比,SPARC 基因敲除脊柱的 NZ 更硬(p<0.001),长度更短(p<0.001)。当跨越条件(SPARC 基因敲除和 WT)对 NZ 长度进行折叠时,串联测试的 IVD 数量对 NZ 长度有影响,但对 NZ 刚度没有影响。相关性分析显示,SPARC 基因敲除小鼠的年龄与 NZ 长度呈弱负相关(r=-0.24),WT 小鼠的年龄与 NZ 刚度呈弱正相关(r=0.30)。总之,无论串联测试的 IVD 数量如何,SPARC 基因敲除小鼠的 NZ 都比 WT 小鼠更硬、更小。这些 IVD 的刚度增加可能会影响这些脊柱关节的活动性,从而可能导致下腰痛。

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