Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells

Bioactive glass (BaG) materials are increasingly used in clinics, but their regulatory mechanisms on osteogenic differentiation remain understudied. In this study, we elucidated the currently unknown role of the p38 MAPK downstream target heat shock protein 27 (HSP27), in the osteogenic commitment o...

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Main Authors: Laura Hyväri, Sari Vanhatupa, Miina Ojansivu, Minna Kelloniemi, Toni-Karri Pakarinen, Leena Hupa, Susanna Miettinen
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/2/224
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author Laura Hyväri
Sari Vanhatupa
Miina Ojansivu
Minna Kelloniemi
Toni-Karri Pakarinen
Leena Hupa
Susanna Miettinen
author_facet Laura Hyväri
Sari Vanhatupa
Miina Ojansivu
Minna Kelloniemi
Toni-Karri Pakarinen
Leena Hupa
Susanna Miettinen
author_sort Laura Hyväri
collection DOAJ
description Bioactive glass (BaG) materials are increasingly used in clinics, but their regulatory mechanisms on osteogenic differentiation remain understudied. In this study, we elucidated the currently unknown role of the p38 MAPK downstream target heat shock protein 27 (HSP27), in the osteogenic commitment of human mesenchymal stem cells (hMSCs), derived from adipose tissue (hASCs) and bone marrow (hBMSCs). Osteogenesis was induced with ionic extract of an experimental BaG in osteogenic medium (OM). Our results showed that BaG OM induced fast osteogenesis of hASCs and hBMSCs, demonstrated by enhanced alkaline phosphatase (ALP) activity, production of extracellular matrix protein collagen type I, and matrix mineralization. BaG OM stimulated early and transient activation of p38/HSP27 signaling by phosphorylation in hMSCs. Inhibition of HSP27 phosphorylation with SB202190 reduced the ALP activity, mineralization, and collagen type I production induced by BaG OM. Furthermore, the reduced pHSP27 protein by SB202190 corresponded to a reduced F-actin intensity of hMSCs. The phosphorylation of HSP27 allowed its co-localization with the cytoskeleton. In terminally differentiated cells, however, pHSP27 was found diffusely in the cytoplasm. This study provides the first evidence that HSP27 is involved in hMSC osteogenesis induced with the ionic dissolution products of BaG. Our results indicate that HSP27 phosphorylation plays a role in the osteogenic commitment of hMSCs, possibly through the interaction with the cytoskeleton.
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spelling doaj.art-2d8d238c0b2b4501b1ac34b0f024825a2023-11-30T21:39:18ZengMDPI AGCells2073-44092023-01-0112222410.3390/cells12020224Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem CellsLaura Hyväri0Sari Vanhatupa1Miina Ojansivu2Minna Kelloniemi3Toni-Karri Pakarinen4Leena Hupa5Susanna Miettinen6Adult Stem Cell Group, BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, FinlandAdult Stem Cell Group, BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, FinlandAdult Stem Cell Group, BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, FinlandDepartment of Plastic and Reconstructive Surgery, Tampere University Hospital, Elämänaukio, Kuntokatu 2, 33520 Tampere, FinlandRegea Cell and Tissue Center, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, FinlandJohan Gadolin Process Chemistry Centre, Åbo Akademi University, Henrikinkatu 2, 20500 Turku, FinlandAdult Stem Cell Group, BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, FinlandBioactive glass (BaG) materials are increasingly used in clinics, but their regulatory mechanisms on osteogenic differentiation remain understudied. In this study, we elucidated the currently unknown role of the p38 MAPK downstream target heat shock protein 27 (HSP27), in the osteogenic commitment of human mesenchymal stem cells (hMSCs), derived from adipose tissue (hASCs) and bone marrow (hBMSCs). Osteogenesis was induced with ionic extract of an experimental BaG in osteogenic medium (OM). Our results showed that BaG OM induced fast osteogenesis of hASCs and hBMSCs, demonstrated by enhanced alkaline phosphatase (ALP) activity, production of extracellular matrix protein collagen type I, and matrix mineralization. BaG OM stimulated early and transient activation of p38/HSP27 signaling by phosphorylation in hMSCs. Inhibition of HSP27 phosphorylation with SB202190 reduced the ALP activity, mineralization, and collagen type I production induced by BaG OM. Furthermore, the reduced pHSP27 protein by SB202190 corresponded to a reduced F-actin intensity of hMSCs. The phosphorylation of HSP27 allowed its co-localization with the cytoskeleton. In terminally differentiated cells, however, pHSP27 was found diffusely in the cytoplasm. This study provides the first evidence that HSP27 is involved in hMSC osteogenesis induced with the ionic dissolution products of BaG. Our results indicate that HSP27 phosphorylation plays a role in the osteogenic commitment of hMSCs, possibly through the interaction with the cytoskeleton.https://www.mdpi.com/2073-4409/12/2/224mesenchymal stem cellsosteogenesisbioactive glassp38/HSP27 signalingphosphorylation
spellingShingle Laura Hyväri
Sari Vanhatupa
Miina Ojansivu
Minna Kelloniemi
Toni-Karri Pakarinen
Leena Hupa
Susanna Miettinen
Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
Cells
mesenchymal stem cells
osteogenesis
bioactive glass
p38/HSP27 signaling
phosphorylation
title Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
title_full Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
title_fullStr Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
title_full_unstemmed Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
title_short Heat Shock Protein 27 Is Involved in the Bioactive Glass Induced Osteogenic Response of Human Mesenchymal Stem Cells
title_sort heat shock protein 27 is involved in the bioactive glass induced osteogenic response of human mesenchymal stem cells
topic mesenchymal stem cells
osteogenesis
bioactive glass
p38/HSP27 signaling
phosphorylation
url https://www.mdpi.com/2073-4409/12/2/224
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