Comparison of transforming growth factor-beta1 and lovastatin on differentiating mesenchymal stem cells toward nucleus pulposus-like phenotype: An in vitro cell culture study

Shu Hua Yang, Kai Chiang Yang, Chih Wei Chen, Ting Chun Huang, Yuan Hui Sun, Ming Hsiao Hu

研究成果: 雜誌貢獻文章

摘要

Study Design: In vitro cell culture study. Purpose: This study aims to investigate the impact of transforming growth factor-beta1 (TGF-ß1) and lovastatin on differentiating human mesenchymal stem cells (MSCs) toward nucleus pulposus (NP)-like phenotype. Overview of Literature: MSCs offer a cell source to the cell-based therapy for intervertebral disc degeneration. TGF-ß1 is used to induce MSCs to differentiate into NP-like cells; however, an undesired expression of collagen type I has been reported. Statins reportedly stimulate expression of bone morphogenetic protein-2 (BMP-2) and promote the chondrogenic phenotype to NP cells. However, the effects of statins with or without TGF-ß1 on the differentiation of MSCs into NP-like cells remain unclear. Methods: Human MSCs were treated with TGF-ß1 alone, lovastatin alone, and simultaneous or sequential treatment with TGF-ß1 and lovastatin. After the proposed stimulation, the total RNA was extracted to assess the expression profile of NP cells-specific genes. Hematoxylin-eosin staining was used for examining the microscopic morphology. Furthermore, we detected the syntheses of S-100 protein, aggrecan, and collagen type II in the extracellular matrix using immunohistochemical staining. Results: Simultaneous or sequential treatment of TGF-ß1 and lovastatin could further augment the BMP-2 overexpression compared with lovastatin-alone treatment. However, the mRNA expression of aggrecan and collagen type II was not compatible with the expression level of BMP-2. Immunohistochemical studies revealed compatible production of aggrecan, collagen type II, and S-100 protein in all three groups treated with lovastatin. Cells in groups treated with lovastatin were less populated than that in the group treated with TGF-ß1 alone. Conclusions: This study demonstrates a promising role of lovastatin in inducing human MSCs into NP-like cells. However, further optimization of cell density before lovastatin treatment, treatment duration, and combination with TGF-ß1 are warranted to attain better stimulatory effects.
原文英語
頁(從 - 到)705-712
頁數8
期刊Asian Spine Journal
13
發行號5
DOIs
出版狀態已發佈 - 一月 1 2019

指紋

Transforming Growth Factor beta1
Lovastatin
Cell Nucleus
Mesenchymal Stromal Cells
Cell Culture Techniques
Phenotype
Aggrecans
Bone Morphogenetic Protein 2
Collagen Type II
Hydroxymethylglutaryl-CoA Reductase Inhibitors
S100 Proteins
Staining and Labeling
Nucleus Pulposus
In Vitro Techniques
Intervertebral Disc Degeneration
Hematoxylin
Eosine Yellowish-(YS)
Cell- and Tissue-Based Therapy
Collagen Type I
Extracellular Matrix

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

引用此文

Comparison of transforming growth factor-beta1 and lovastatin on differentiating mesenchymal stem cells toward nucleus pulposus-like phenotype : An in vitro cell culture study. / Yang, Shu Hua; Yang, Kai Chiang; Chen, Chih Wei; Huang, Ting Chun; Sun, Yuan Hui; Hu, Ming Hsiao.

於: Asian Spine Journal, 卷 13, 編號 5, 01.01.2019, p. 705-712.

研究成果: 雜誌貢獻文章

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title = "Comparison of transforming growth factor-beta1 and lovastatin on differentiating mesenchymal stem cells toward nucleus pulposus-like phenotype: An in vitro cell culture study",
abstract = "Study Design: In vitro cell culture study. Purpose: This study aims to investigate the impact of transforming growth factor-beta1 (TGF-{\ss}1) and lovastatin on differentiating human mesenchymal stem cells (MSCs) toward nucleus pulposus (NP)-like phenotype. Overview of Literature: MSCs offer a cell source to the cell-based therapy for intervertebral disc degeneration. TGF-{\ss}1 is used to induce MSCs to differentiate into NP-like cells; however, an undesired expression of collagen type I has been reported. Statins reportedly stimulate expression of bone morphogenetic protein-2 (BMP-2) and promote the chondrogenic phenotype to NP cells. However, the effects of statins with or without TGF-{\ss}1 on the differentiation of MSCs into NP-like cells remain unclear. Methods: Human MSCs were treated with TGF-{\ss}1 alone, lovastatin alone, and simultaneous or sequential treatment with TGF-{\ss}1 and lovastatin. After the proposed stimulation, the total RNA was extracted to assess the expression profile of NP cells-specific genes. Hematoxylin-eosin staining was used for examining the microscopic morphology. Furthermore, we detected the syntheses of S-100 protein, aggrecan, and collagen type II in the extracellular matrix using immunohistochemical staining. Results: Simultaneous or sequential treatment of TGF-{\ss}1 and lovastatin could further augment the BMP-2 overexpression compared with lovastatin-alone treatment. However, the mRNA expression of aggrecan and collagen type II was not compatible with the expression level of BMP-2. Immunohistochemical studies revealed compatible production of aggrecan, collagen type II, and S-100 protein in all three groups treated with lovastatin. Cells in groups treated with lovastatin were less populated than that in the group treated with TGF-{\ss}1 alone. Conclusions: This study demonstrates a promising role of lovastatin in inducing human MSCs into NP-like cells. However, further optimization of cell density before lovastatin treatment, treatment duration, and combination with TGF-{\ss}1 are warranted to attain better stimulatory effects.",
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T1 - Comparison of transforming growth factor-beta1 and lovastatin on differentiating mesenchymal stem cells toward nucleus pulposus-like phenotype

T2 - An in vitro cell culture study

AU - Yang, Shu Hua

AU - Yang, Kai Chiang

AU - Chen, Chih Wei

AU - Huang, Ting Chun

AU - Sun, Yuan Hui

AU - Hu, Ming Hsiao

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Study Design: In vitro cell culture study. Purpose: This study aims to investigate the impact of transforming growth factor-beta1 (TGF-ß1) and lovastatin on differentiating human mesenchymal stem cells (MSCs) toward nucleus pulposus (NP)-like phenotype. Overview of Literature: MSCs offer a cell source to the cell-based therapy for intervertebral disc degeneration. TGF-ß1 is used to induce MSCs to differentiate into NP-like cells; however, an undesired expression of collagen type I has been reported. Statins reportedly stimulate expression of bone morphogenetic protein-2 (BMP-2) and promote the chondrogenic phenotype to NP cells. However, the effects of statins with or without TGF-ß1 on the differentiation of MSCs into NP-like cells remain unclear. Methods: Human MSCs were treated with TGF-ß1 alone, lovastatin alone, and simultaneous or sequential treatment with TGF-ß1 and lovastatin. After the proposed stimulation, the total RNA was extracted to assess the expression profile of NP cells-specific genes. Hematoxylin-eosin staining was used for examining the microscopic morphology. Furthermore, we detected the syntheses of S-100 protein, aggrecan, and collagen type II in the extracellular matrix using immunohistochemical staining. Results: Simultaneous or sequential treatment of TGF-ß1 and lovastatin could further augment the BMP-2 overexpression compared with lovastatin-alone treatment. However, the mRNA expression of aggrecan and collagen type II was not compatible with the expression level of BMP-2. Immunohistochemical studies revealed compatible production of aggrecan, collagen type II, and S-100 protein in all three groups treated with lovastatin. Cells in groups treated with lovastatin were less populated than that in the group treated with TGF-ß1 alone. Conclusions: This study demonstrates a promising role of lovastatin in inducing human MSCs into NP-like cells. However, further optimization of cell density before lovastatin treatment, treatment duration, and combination with TGF-ß1 are warranted to attain better stimulatory effects.

AB - Study Design: In vitro cell culture study. Purpose: This study aims to investigate the impact of transforming growth factor-beta1 (TGF-ß1) and lovastatin on differentiating human mesenchymal stem cells (MSCs) toward nucleus pulposus (NP)-like phenotype. Overview of Literature: MSCs offer a cell source to the cell-based therapy for intervertebral disc degeneration. TGF-ß1 is used to induce MSCs to differentiate into NP-like cells; however, an undesired expression of collagen type I has been reported. Statins reportedly stimulate expression of bone morphogenetic protein-2 (BMP-2) and promote the chondrogenic phenotype to NP cells. However, the effects of statins with or without TGF-ß1 on the differentiation of MSCs into NP-like cells remain unclear. Methods: Human MSCs were treated with TGF-ß1 alone, lovastatin alone, and simultaneous or sequential treatment with TGF-ß1 and lovastatin. After the proposed stimulation, the total RNA was extracted to assess the expression profile of NP cells-specific genes. Hematoxylin-eosin staining was used for examining the microscopic morphology. Furthermore, we detected the syntheses of S-100 protein, aggrecan, and collagen type II in the extracellular matrix using immunohistochemical staining. Results: Simultaneous or sequential treatment of TGF-ß1 and lovastatin could further augment the BMP-2 overexpression compared with lovastatin-alone treatment. However, the mRNA expression of aggrecan and collagen type II was not compatible with the expression level of BMP-2. Immunohistochemical studies revealed compatible production of aggrecan, collagen type II, and S-100 protein in all three groups treated with lovastatin. Cells in groups treated with lovastatin were less populated than that in the group treated with TGF-ß1 alone. Conclusions: This study demonstrates a promising role of lovastatin in inducing human MSCs into NP-like cells. However, further optimization of cell density before lovastatin treatment, treatment duration, and combination with TGF-ß1 are warranted to attain better stimulatory effects.

KW - Intervertebral disc degeneration

KW - Lovastatin

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KW - Nucleus pulposus-like cells

KW - Spine

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