MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

Abstract Mesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs deriv...

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Main Authors: Kulisara Marupanthorn, Chairat Tantrawatpan, Pakpoom Kheolamai, Duangrat Tantikanlayaporn, Sirikul Manochantr
Format: Article
Language:English
Published: Nature Portfolio 2021-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-87298-5
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author Kulisara Marupanthorn
Chairat Tantrawatpan
Pakpoom Kheolamai
Duangrat Tantikanlayaporn
Sirikul Manochantr
author_facet Kulisara Marupanthorn
Chairat Tantrawatpan
Pakpoom Kheolamai
Duangrat Tantikanlayaporn
Sirikul Manochantr
author_sort Kulisara Marupanthorn
collection DOAJ
description Abstract Mesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.
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spelling doaj.art-2653dcde4ece49c8b7d2d64f39afac9d2022-12-21T21:20:49ZengNature PortfolioScientific Reports2045-23222021-04-0111111710.1038/s41598-021-87298-5MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placentaKulisara Marupanthorn0Chairat Tantrawatpan1Pakpoom Kheolamai2Duangrat Tantikanlayaporn3Sirikul Manochantr4Department of Agricultural Technology and Development, Faculty of Agricultural Technology, Chiangmai Rajabhat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityAbstract Mesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.https://doi.org/10.1038/s41598-021-87298-5
spellingShingle Kulisara Marupanthorn
Chairat Tantrawatpan
Pakpoom Kheolamai
Duangrat Tantikanlayaporn
Sirikul Manochantr
MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
Scientific Reports
title MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
title_full MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
title_fullStr MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
title_full_unstemmed MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
title_short MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
title_sort microrna treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta
url https://doi.org/10.1038/s41598-021-87298-5
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