Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice.

Intervertebral disc degeneration and ectopic bone formation in apolipoprotein E knockout mice.
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DOI:
10.1002/jor.22216
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发表时间:
2013-02
影响因子:
2.8
通讯作者:
Li, Xudong
Li, Xudong
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Dawei;Jin, Li;Reames, Davis L.;Shen, Francis H.;Shimer, Adam L.;Li, Xudong

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已知心血管危险因素与椎间盘退变有关,但其潜在机制尚不清楚。ApoE敲除(KO)小鼠是一种成熟的关节硬化模型。我们假设ApoE可能参与维持椎间盘健康,ApoE KO小鼠发生早期椎间盘退变。采用组织学/免疫学、生化和实时RT-PCR检测ApoE KO和野生型(WT)小鼠的椎间盘。在椎间盘细胞中也进行了细胞外基质生产的比较。我们发现ApoE在WT型椎间盘终板中高表达,ApoE KO型椎间盘终板中形成异位骨。ApoE KO纤维环(AF)和髓核(NP)细胞中糖胺聚糖含量均降低。AF细胞中胶原蛋白水平升高,NP细胞中胶原蛋白水平降低。基质金属蛋白酶-3、9和13的表达增加,这可能部分解释了基质生成受损的原因。我们还发现AF细胞中胶原I、II、aggrecan和biglycan mRNA表达增加,而NP细胞中胶原I、II、aggrecan和biglycan mRNA表达减少。ApoE KO NP组细胞凋亡增加。这些结果提示ApoE KO小鼠早期椎间盘退变发生改变。ApoE,加上它对心血管疾病的重要性,可能在椎间盘完整性和功能中起关键作用。
Cardiovascular risk factors are known to be associated with intervertebral disc degeneration, but the underlying mechanism is still unclear. ApoE knockout (KO) mouse is a well-established model for arthrosclerosis. We hypothesize that ApoE may involve in maintaining disc health and ApoE KO mouse develops early disc degeneration. Discs of ApoE KO and wild-type (WT) mice were characterized with histological/immunological, biochemical, and real time RT-PCR assays. A comparison of the extracellular matrix production was also performed in disc cells. We demonstrated that ApoE was highly expressed in the endplates of WT discs and ectopic bone formed in the endplates of ApoE KO discs. Glycosaminoglycan content was decreased in both ApoE KO annulus fibrosus (AF) and nucleus pulpsous (NP) cells. Collagen levels were increased in AF and decreased in NP cells. Matrix metalloproteinases-3, 9, and 13 expression was increased which may partially explain the impaired matrix production. We also found increased collagen I, II, aggrecan and biglycan mRNA expressions in AF cells but decreased in NP cells. Apoptosis was increased in the ApoE KO NP tissue. These results suggest early disc degeneration changes in ApoE KO mice. ApoE, plus its importance to cardiovascular disease, may play a critical role in disc integrity and function.
DOI: 10.1002/jor.21206
发表时间: 2011-01
影响因子: 2.8
作者:
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发表时间: 2010-03-01
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DOI: 10.1016/j.spinee.2007.07.392
发表时间: 2008-09-01
期刊: SPINE JOURNAL
影响因子: 4.5
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DOI: 10.1161/01.atv.14.1.133
发表时间: 1994-01-01
期刊: ARTERIOSCLEROSIS AND THROMBOSIS
影响因子: --
作者:
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