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脐带间充质干细胞条件培养基恢复了暴露于高糖环境中的髓核间充质干细胞中Ⅱ型胶原和聚集蛋白聚糖的表达。

Umbilical cord mesenchymal stem cell conditioned medium restored the expression of collagen II and aggrecan in nucleus pulposus mesenchymal stem cells exposed to high glucose.

机构信息

Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

Cryomedicine Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, People's Republic of China.

出版信息

J Bone Miner Metab. 2019 May;37(3):455-466. doi: 10.1007/s00774-018-0953-9. Epub 2018 Sep 5.

DOI:10.1007/s00774-018-0953-9
PMID:30187277
Abstract

Diabetes can cause intervertebral disc degeneration by accelerating apoptosis and senescence of nucleus pulposus mesenchymal stem cells (NPMSCs). The aim of this study was to determine the effect of umbilical cord mesenchymal stem cells (UCMSCs) conditioned medium on high glucose (HG) induced degradation of NPMSCs produced extracellular matrix. NPMSCs were isolated from the inner intervertebral disc tissue using type XI collagenase digestion. According to Annexin V/propidium iodide (PI) flow cytometry analysis; HG leads to an increase in the rate of NPMSCs apoptosis. HG injury also resulted in a marked decrease in the percentage of cells in G0/G1 phase and an increase in cells in S and G2/M phases, indicating that HG induces cell cycle arrest of NPMSCs. Treatment with MSC-CM abolished the effect of HG on cell senescence. HG also significantly inhibited collagen II and aggrecan expression in NPMSCs. After MSC-CM treatment, the expression of these two extracellular matrix components was restored. Exposure to HG resulted in phosphorylation of p38 MAPK, while the levels of total p38 MAPK were not affected. When treated with MSC-CM, phosphorylated p38 MAPK levels of NPMSCs were lower than those without CM treatment. Our data also showed that p38 MAPK inhibitor SB203580 can attenuated phosphorylation of p38 MAPK and resumed the collagen II and aggrecan expression in NPMSCs. In summary, this study demonstrated that MSC-CM has the potential to alleviate HG induced extracellular matrix degradation via the p38 MAPK pathway.

摘要

糖尿病可通过加速髓核间充质干细胞(NPMSCs)凋亡和衰老导致椎间盘退变。本研究旨在确定脐带间充质干细胞(UCMSCs)条件培养基对高糖(HG)诱导 NPMSCs 产生细胞外基质降解的影响。NPMSCs 采用 XI 型胶原酶消化法从椎间盘内组织中分离得到。根据 Annexin V/碘化丙啶(PI)流式细胞术分析;HG 导致 NPMSCs 凋亡率增加。HG 损伤还导致 G0/G1 期细胞的百分比明显下降,S 和 G2/M 期细胞增加,表明 HG 诱导 NPMSCs 细胞周期停滞。MSC-CM 处理消除了 HG 对细胞衰老的影响。HG 还显著抑制 NPMSCs 中胶原 II 和聚集蛋白聚糖的表达。经 MSC-CM 处理后,这两种细胞外基质成分的表达得到恢复。HG 暴露导致 p38 MAPK 磷酸化,而总 p38 MAPK 水平不受影响。用 MSC-CM 处理后,NPMSCs 中磷酸化 p38 MAPK 的水平低于无 CM 处理组。我们的数据还表明,p38 MAPK 抑制剂 SB203580 可以减弱 p38 MAPK 的磷酸化,并恢复 NPMSCs 中胶原 II 和聚集蛋白聚糖的表达。综上所述,本研究表明,MSC-CM 通过 p38 MAPK 通路具有减轻 HG 诱导的细胞外基质降解的潜力。

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