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Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties

BACKGROUND: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse e...

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Autores principales: Zarychta-Wiśniewska, Weronika, Burdzinska, Anna, Kulesza, Agnieszka, Gala, Kamila, Kaleta, Beata, Zielniok, Katarzyna, Siennicka, Katarzyna, Sabat, Marek, Paczek, Leszek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316159/
https://www.ncbi.nlm.nih.gov/pubmed/28214472
http://dx.doi.org/10.1186/s12860-017-0129-9
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author Zarychta-Wiśniewska, Weronika
Burdzinska, Anna
Kulesza, Agnieszka
Gala, Kamila
Kaleta, Beata
Zielniok, Katarzyna
Siennicka, Katarzyna
Sabat, Marek
Paczek, Leszek
author_facet Zarychta-Wiśniewska, Weronika
Burdzinska, Anna
Kulesza, Agnieszka
Gala, Kamila
Kaleta, Beata
Zielniok, Katarzyna
Siennicka, Katarzyna
Sabat, Marek
Paczek, Leszek
author_sort Zarychta-Wiśniewska, Weronika
collection PubMed
description BACKGROUND: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population. RESULTS: Human ASCs from 6 healthy donors were treated or not with BMP-12 (50 or 100 ng/ml, 7 days) and tested for gene expression (COLL1, SCX, MKH, DCN, TNC, RUNX2), protein expression (COLL1, COLL3, MKH), proliferation, migration, secretory activity, immunomodulatory properties and susceptibility to oxidative stress. RT-PCR revealed up-regulation of SCX, MKH and RUNX2 genes in BMP-12 treated cells (2.05, 2.65 and 1.87 fold in comparison to control, respectively, p < 0.05) and Western Blot revealed significant increase of COLL1 and MHK expression after BMP-12 treatment. Addition of BMP-12 significantly enhanced secretion of VEGF, IL-6, MMP-1 and MPP-8 by hASCs while had no effect on TGF-β, IL-10, EGF and MMP-13. Moreover, BMP-12 presence in medium attenuated inhibitory effect of hASCs on allo-activated lymphocytes proliferation. At the same time BMP-12 displayed no influence on hASCs proliferation, migration and susceptibility to oxidative stress. CONCLUSION: BMP-12 activates tenogenic pathway in hASCs but also affects secretory activity and impairs immunomodulatory potential of this population that can influence the clinical outcome after cell transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-017-0129-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-53161592017-02-24 Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties Zarychta-Wiśniewska, Weronika Burdzinska, Anna Kulesza, Agnieszka Gala, Kamila Kaleta, Beata Zielniok, Katarzyna Siennicka, Katarzyna Sabat, Marek Paczek, Leszek BMC Cell Biol Research Article BACKGROUND: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population. RESULTS: Human ASCs from 6 healthy donors were treated or not with BMP-12 (50 or 100 ng/ml, 7 days) and tested for gene expression (COLL1, SCX, MKH, DCN, TNC, RUNX2), protein expression (COLL1, COLL3, MKH), proliferation, migration, secretory activity, immunomodulatory properties and susceptibility to oxidative stress. RT-PCR revealed up-regulation of SCX, MKH and RUNX2 genes in BMP-12 treated cells (2.05, 2.65 and 1.87 fold in comparison to control, respectively, p < 0.05) and Western Blot revealed significant increase of COLL1 and MHK expression after BMP-12 treatment. Addition of BMP-12 significantly enhanced secretion of VEGF, IL-6, MMP-1 and MPP-8 by hASCs while had no effect on TGF-β, IL-10, EGF and MMP-13. Moreover, BMP-12 presence in medium attenuated inhibitory effect of hASCs on allo-activated lymphocytes proliferation. At the same time BMP-12 displayed no influence on hASCs proliferation, migration and susceptibility to oxidative stress. CONCLUSION: BMP-12 activates tenogenic pathway in hASCs but also affects secretory activity and impairs immunomodulatory potential of this population that can influence the clinical outcome after cell transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-017-0129-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-18 /pmc/articles/PMC5316159/ /pubmed/28214472 http://dx.doi.org/10.1186/s12860-017-0129-9 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zarychta-Wiśniewska, Weronika
Burdzinska, Anna
Kulesza, Agnieszka
Gala, Kamila
Kaleta, Beata
Zielniok, Katarzyna
Siennicka, Katarzyna
Sabat, Marek
Paczek, Leszek
Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
title Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
title_full Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
title_fullStr Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
title_full_unstemmed Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
title_short Bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
title_sort bmp-12 activates tenogenic pathway in human adipose stem cells and affects their immunomodulatory and secretory properties
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316159/
https://www.ncbi.nlm.nih.gov/pubmed/28214472
http://dx.doi.org/10.1186/s12860-017-0129-9
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