Cargando…

Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor

The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraper...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Du-Hwan, Noh, Sun-Up, Chae, Seoung-Wan, Kim, Sang-Jun, Lee, Yong-Taek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396498/
https://www.ncbi.nlm.nih.gov/pubmed/34445689
http://dx.doi.org/10.3390/ijms22168983
_version_ 1783744386611281920
author Kim, Du-Hwan
Noh, Sun-Up
Chae, Seoung-Wan
Kim, Sang-Jun
Lee, Yong-Taek
author_facet Kim, Du-Hwan
Noh, Sun-Up
Chae, Seoung-Wan
Kim, Sang-Jun
Lee, Yong-Taek
author_sort Kim, Du-Hwan
collection PubMed
description The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study.
format Online
Article
Text
id pubmed-8396498
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83964982021-08-28 Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor Kim, Du-Hwan Noh, Sun-Up Chae, Seoung-Wan Kim, Sang-Jun Lee, Yong-Taek Int J Mol Sci Article The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study. MDPI 2021-08-20 /pmc/articles/PMC8396498/ /pubmed/34445689 http://dx.doi.org/10.3390/ijms22168983 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Du-Hwan
Noh, Sun-Up
Chae, Seoung-Wan
Kim, Sang-Jun
Lee, Yong-Taek
Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
title Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
title_full Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
title_fullStr Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
title_full_unstemmed Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
title_short Altered Differentiation of Tendon-Derived Stem Cells in Diabetic Conditions Mediated by Macrophage Migration Inhibitory Factor
title_sort altered differentiation of tendon-derived stem cells in diabetic conditions mediated by macrophage migration inhibitory factor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396498/
https://www.ncbi.nlm.nih.gov/pubmed/34445689
http://dx.doi.org/10.3390/ijms22168983
work_keys_str_mv AT kimduhwan altereddifferentiationoftendonderivedstemcellsindiabeticconditionsmediatedbymacrophagemigrationinhibitoryfactor
AT nohsunup altereddifferentiationoftendonderivedstemcellsindiabeticconditionsmediatedbymacrophagemigrationinhibitoryfactor
AT chaeseoungwan altereddifferentiationoftendonderivedstemcellsindiabeticconditionsmediatedbymacrophagemigrationinhibitoryfactor
AT kimsangjun altereddifferentiationoftendonderivedstemcellsindiabeticconditionsmediatedbymacrophagemigrationinhibitoryfactor
AT leeyongtaek altereddifferentiationoftendonderivedstemcellsindiabeticconditionsmediatedbymacrophagemigrationinhibitoryfactor