Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we i...

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Main Authors: Angela P. Bastidas-Coral, Astrid D. Bakker, Behrouz Zandieh-Doulabi, Cornelis J. Kleverlaan, Nathalie Bravenboer, Tim Forouzanfar, Jenneke Klein-Nulend
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/1318256
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author Angela P. Bastidas-Coral
Astrid D. Bakker
Behrouz Zandieh-Doulabi
Cornelis J. Kleverlaan
Nathalie Bravenboer
Tim Forouzanfar
Jenneke Klein-Nulend
author_facet Angela P. Bastidas-Coral
Astrid D. Bakker
Behrouz Zandieh-Doulabi
Cornelis J. Kleverlaan
Nathalie Bravenboer
Tim Forouzanfar
Jenneke Klein-Nulend
author_sort Angela P. Bastidas-Coral
collection DOAJ
description During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs). hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL) for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold), as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair.
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spelling doaj-art-ad08bc2daa5b4aa4b3dcb6e693ed00c22025-02-03T01:30:34ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/13182561318256Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem CellsAngela P. Bastidas-Coral0Astrid D. Bakker1Behrouz Zandieh-Doulabi2Cornelis J. Kleverlaan3Nathalie Bravenboer4Tim Forouzanfar5Jenneke Klein-Nulend6Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDepartment of Dental Materials Science, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDepartment of Clinical Chemistry, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDepartment of Oral and Maxillofacial Surgery, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDepartment of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, NetherlandsDuring the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs). hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL) for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold), as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair.http://dx.doi.org/10.1155/2016/1318256
spellingShingle Angela P. Bastidas-Coral
Astrid D. Bakker
Behrouz Zandieh-Doulabi
Cornelis J. Kleverlaan
Nathalie Bravenboer
Tim Forouzanfar
Jenneke Klein-Nulend
Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells
Stem Cells International
title Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells
title_full Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells
title_fullStr Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells
title_full_unstemmed Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells
title_short Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells
title_sort cytokines tnf α il 6 il 17f and il 4 differentially affect osteogenic differentiation of human adipose stem cells
url http://dx.doi.org/10.1155/2016/1318256
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