Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc

Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc
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DOI:
10.1097/00007632-199705150-00006
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发表时间:
1997-05-15
期刊:
影响因子:
3
通讯作者:
Obata, K
Obata, K
中科院分区:
医学2区
文献类型:
--
作者:
Handa, T;Ishihara, H;Obata, K

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研究设计.这项研究是一个独特的在体外研究静水压力对人类椎间盘代谢的影响。研究静水压力对人腰椎间盘基质合成和基质金属蛋白酶产生的影响。机械应力和静水压力影响牛关节软骨和尾骨椎间盘中蛋白多糖和蛋白质的合成速率。然而,椎间盘在机械应力作用下基质合成调控的机制尚未阐明。使用了28个从手术和尸检尸体中获得的人腰椎间盘。在塑料注射器中向每个组织部分中加入培养基,并置于充满水的流体静压控制容器中。施加的流体静压为1(对照)、3和30 atm(atm =大气压),持续2小时。放射性同位素掺入法测定蛋白多糖和蛋白质合成速率。用单克隆抗体一步酶联免疫法测定基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶组织抑制剂-1(TIMP-1)的含量。三个大气压的压力刺激蛋白多糖的合成率在髓核和内环(n = 14,在每个组织)。与对照组相比,30 atm压力明显抑制髓核内纤维环蛋白多糖的合成(P = 0.011),髓核基质金属蛋白酶-3的合成在30 atm压力下比3atm压力下增加(P = 0.014,n = 16)。金属蛋白酶-1产生的最高组织抑制剂在3个大气压下在内环中显示出最高值(每个组织n = 16)。结论。结果表明,静水压力影响椎间盘细胞代谢。生理水平的静水压力(3个大气压)可以作为一个合成代谢因子,刺激蛋白聚糖合成和金属蛋白酶-1的组织抑制剂的生产。这对于维持椎间盘基质可能是必不可少的。如果压力为30个大气压或更小或1个大气压或更小,则分解代谢作用将占主导地位,蛋白聚糖合成速率降低,基质金属蛋白酶-3产量增加。因此,异常的静水压力可能加速椎间盘退变。
Study Design. This study is a unique in vitro study on the effects of hydrostatic pressure on human intervertebral disc metabolism.Objective. To investigate the effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc.Summary of Background Data. Mechanical stress and hydrostatic pressures influence proteoglycan and protein synthesis rates in bovine articular cartilage and coccygeal discs. However, the mechanism of matrix synthesis regulation of the intervertebral disc under mechanical stress has not been elucidated.Methods. Twenty-eight human lumbar intervertebral discs obtained from surgery and from cadavers at autopsy were used. Each tissue fraction was charged with medium in a plastic syringe and placed in a water-filled hydrostatic pressure-control vessel. The hydrostatic pressures applied were 1 (control), 3, and 30 atm (atm = atmospheres) for 2 hours. The proteoglycan and protein synthesis rates were determined by radioisotope incorporation. The production of matrix metallaproteinase-3 and tissue inhibitor of metalloproteinases-1 were measured by a one-step enzyme immunoassay method using monoclonal antibodies.Results. Three atm pressure stimulated proteoglycan synthesis rates in the nucleus pulposus and inner anulus (n = 14 in each tissue). Compared with the control group, 30 atm pressure significantly inhibited proteoglycan synthesis in the inner anulus (P = 0.011), In the nucleus pulposus, matrix metalloproteinase-3 production was stimulated at a pressure of 30 atm relative to 3 atm (P = 0.014, n = 16 in each tissue). The highest tissue inhibitor of metalloproteinases-1 production showed highest values at 3 atm pressure in the inner anulus (n = 16 in each tissue).Conclusion. The results suggest that hydrostatic pressure influences intervertebral disc cell metabolism. A physiologic level of hydrostatic pressure (3 atm) may act as an anabolic factor for stimulation of proteoglycan synthesis and tissue inhibitor of metalloproteinases-1 production. This may be essential for maintaining the matrix of the disc. if the pressure was 30 atm or mote or 1 atm or less, a catabolic effect will be predominant, with reduction of proteoglycan synthesis rate and increase of matrix metalloproteinase-3 production. Abnormal hydrostatic pressure, therefore, may accelerate disc degeneration.