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首页> 外文期刊>Artificial Organs >Lovastatin promotes redifferentiation of human nucleus pulposus cells during expansion in monolayer culture.
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Lovastatin promotes redifferentiation of human nucleus pulposus cells during expansion in monolayer culture.

机译：洛伐他汀在单层培养的扩增过程中促进人髓核细胞的再分化。

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摘要

To acquire the capacities for matrix production and preservation of an expanded volume within a damaged intervertebral disc (IVD), cells isolated from human nucleus pulposus (NP) tissues must undergo several passages in monolayer culture. However, chondrocytes and IVD cells in monolayer culture undergo dedifferentiation, increased synthesis of type I collagen, thereby compromising the properties of regenerative tissues. The present study was undertaken to ascertain whether lovastatin reverses "dedifferentiation" of human NP cells during monolayer expansion. Expression of genes encoding type II collagen and transcription factor SOX9 in these cells was upregulated by lovastatin, with maximal stimulations observed at 5 microM, whereas type I collagen gene expression was suppressed by the drug, with maximal inhibitions observed at 5-10 microM. At lovastatin concentrations >/=1 microM, expression of genes encoding the bone morphogenetic proteins BMP-2 and BMP-7 was also significantly enhanced. Furthermore, the number of NP cells exhibiting a rounded shape and positive staining for S-100 protein and type II collagen protein increased during treatment with lovastatin. These findings strongly support the induction by lovastatin of "redifferentiation" of human NP cells during their expansion in monolayer culture.
机译：为了获得基质生产和受损椎间盘（IVD）内扩大体积保存的能力，从人髓核（NP）组织分离的细胞必须在单层培养中经历数次传代。然而，单层培养中的软骨细胞和IVD细胞经历去分化，增加了I型胶原蛋白的合成，从而损害了再生组织的特性。进行本研究以确定洛伐他汀是否在单层扩增过程中逆转人NP细胞的“去分化”。洛伐他汀上调这些细胞中编码II型胶原蛋白和转录因子SOX9的基因的表达，在5 microM处观察到最大的刺激，而在药物中抑制I型胶原蛋白基因的表达，在5-10 microM处观察到最大的抑制作用。在洛伐他汀浓度> / = 1 microM时，编码骨形态发生蛋白BMP-2和BMP-7的基因的表达也显着增强。此外，在用洛伐他汀治疗期间，表现出圆形形状且S-100蛋白和II型胶原蛋白呈阳性染色的NP细胞数量增加。这些发现强烈支持洛伐他汀诱导人NP细胞在单层培养中扩增过程中的“再分化”。

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