Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 20520-20532 |
| Journal | Journal of Cellular Physiology |
| Volume | 234 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2019 |
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IL-6 counteracts the inhibitory effect of IL-4 on osteogenic differentiation of human adipose stem cells. / Bastidas-Coral, Angela P.; Hogervorst, Jolanda M. A.; Forouzanfar, Tymour; Kleverlaan, Cornelis J.; Koolwijk, Pieter; Klein-Nulend, Jenneke; Bakker, Astrid D.
In: Journal of Cellular Physiology, Vol. 234, No. 11, 2019, p. 20520-20532.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - IL-6 counteracts the inhibitory effect of IL-4 on osteogenic differentiation of human adipose stem cells
AU - Bastidas-Coral, Angela P.
AU - Hogervorst, Jolanda M. A.
AU - Forouzanfar, Tymour
AU - Kleverlaan, Cornelis J.
AU - Koolwijk, Pieter
AU - Klein-Nulend, Jenneke
AU - Bakker, Astrid D.
PY - 2019
Y1 - 2019
N2 - Fracture repair is characterized by cytokine production and hypoxia. To better predict cytokine modulation of mesenchymal stem cell (MSC)-aided bone healing, we investigated whether interleukin 4 (IL-4), IL-6, and their combination, affect osteogenic differentiation, vascular endothelial growth factor (VEGF) production, and/or mammalian target of rapamycin complex 1 (mTORC1) activation by MSCs under normoxia or hypoxia. Human adipose stem cells (hASCs) were cultured with IL-4, IL-6, or their combination for 3 days under normoxia (20% O 2) or hypoxia (1% O 2), followed by 11 days without cytokines under normoxia or hypoxia. Hypoxia did not alter IL-4 or IL-6-modulated gene or protein expression by hASCs. IL-4 alone decreased runt-related transcription factor 2 (RUNX2) and collagen type 1 (COL1) gene expression, alkaline phosphatase (ALP) activity, and VEGF protein production by hASCs under normoxia and hypoxia, and decreased mineralization of hASCs under hypoxia. In contrast, IL-6 increased mineralization of hASCs under normoxia, and enhanced RUNX2 gene expression under normoxia and hypoxia. Neither IL-4 nor IL-6 affected phosphorylation of the mTORC1 effector protein P70S6K. IL-4 combined with IL-6 diminished the inhibitory effect of IL-4 on ALP activity, bone nodule formation, and VEGF production, and decreased RUNX2 and COL1 expression, similar to IL-4 alone, under normoxia and hypoxia. In conclusion, IL-4 alone, but not in combination with IL-6, inhibits osteogenic differentiation and angiogenic stimulation potential of hASCs under normoxia and hypoxia, likely through pathways other than mTORC1. These results indicate that cytokines may differentially affect bone healing and regeneration when applied in isolation or in combination.
AB - Fracture repair is characterized by cytokine production and hypoxia. To better predict cytokine modulation of mesenchymal stem cell (MSC)-aided bone healing, we investigated whether interleukin 4 (IL-4), IL-6, and their combination, affect osteogenic differentiation, vascular endothelial growth factor (VEGF) production, and/or mammalian target of rapamycin complex 1 (mTORC1) activation by MSCs under normoxia or hypoxia. Human adipose stem cells (hASCs) were cultured with IL-4, IL-6, or their combination for 3 days under normoxia (20% O 2) or hypoxia (1% O 2), followed by 11 days without cytokines under normoxia or hypoxia. Hypoxia did not alter IL-4 or IL-6-modulated gene or protein expression by hASCs. IL-4 alone decreased runt-related transcription factor 2 (RUNX2) and collagen type 1 (COL1) gene expression, alkaline phosphatase (ALP) activity, and VEGF protein production by hASCs under normoxia and hypoxia, and decreased mineralization of hASCs under hypoxia. In contrast, IL-6 increased mineralization of hASCs under normoxia, and enhanced RUNX2 gene expression under normoxia and hypoxia. Neither IL-4 nor IL-6 affected phosphorylation of the mTORC1 effector protein P70S6K. IL-4 combined with IL-6 diminished the inhibitory effect of IL-4 on ALP activity, bone nodule formation, and VEGF production, and decreased RUNX2 and COL1 expression, similar to IL-4 alone, under normoxia and hypoxia. In conclusion, IL-4 alone, but not in combination with IL-6, inhibits osteogenic differentiation and angiogenic stimulation potential of hASCs under normoxia and hypoxia, likely through pathways other than mTORC1. These results indicate that cytokines may differentially affect bone healing and regeneration when applied in isolation or in combination.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069724314&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31016754
U2 - 10.1002/jcp.28652
DO - 10.1002/jcp.28652
M3 - Article
VL - 234
SP - 20520
EP - 20532
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 11
ER -