Effect of high glucose on stress-induced senescence of nucleus pulposus cells of adult rats.
Effect of high glucose on stress-induced senescence of nucleus pulposus cells of adult rats.
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DOI：
10.4184/asj.2015.9.2.155
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发表时间：
2015-04
影响因子：
2.3
通讯作者：
Park EY
中科院分区：
文献类型：
--
作者：
Kong JG;Park JB;Lee D;Park EY
体外细胞培养模型。观察糖尿病(DM)对成人髓核(NP)细胞衰老的影响。糖尿病是世界范围内的一个主要公共卫生问题，尤其是成人起病(2型)糖尿病。糖尿病也被认为是椎间盘退变的重要病因。高血糖被认为是糖尿病相关疾病通过衰老发展的一个主要原因。然而，DM对成年NP细胞衰老的影响知之甚少。从24周龄大鼠分离出成年NP细胞，培养后分别置于10%胎牛血清(FBS，正常对照组)和10%FBS+两种不同的高浓度葡萄糖(0.1M或0.2M；实验条件)中培养1天或3天。我们用衰老相关β-半乳糖苷酶(SA-β-GAL)染色对成年大鼠NP细胞衰老的发生进行了鉴定和定量。我们还研究了与复制衰老(p53-p21-pRB)和应激诱导的早衰(p16-pRB)途径相关的蛋白的表达。成年大鼠NP细胞经高糖处理后，SA-β-Gal平均阳性百分率增加，呈剂量和时间依赖关系。两种高糖水平均可增加成年大鼠NP细胞p16和pRb蛋白的表达。然而，在两种高糖浓度下，成年大鼠NP细胞的p53和p21蛋白水平均降低。目前的研究表明，高糖以剂量和时间依赖的方式加速应激诱导的成年大鼠NP细胞衰老。成人NP细胞加速应激诱导的衰老可能是老年DM患者椎间盘退变的一个新的危险因素。这些结果表明，严格的血糖控制对于预防或延缓老年糖尿病患者的腰椎间盘退变是重要的。
In vitro cell culture model. We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells. DM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells. Adult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-β-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways. The mean SA-β-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations. The current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM.