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

Laura Hyväri; Sari Vanhatupa; Miina Ojansivu; Minna Kelloniemi; Toni-Karri Pakarinen; Leena Hupa; Susanna Miettinen

doi:10.3390/cells12020224

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

Cells. 2023 Jan 5;12(2):224. doi: 10.3390/cells12020224.

Authors

Laura Hyväri^{1

2}, Sari Vanhatupa^{1

2}, Miina Ojansivu^{1

2}, Minna Kelloniemi³, Toni-Karri Pakarinen⁴, Leena Hupa⁵, Susanna Miettinen^{1

2}

Affiliations

¹ Adult Stem Cell Group, BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland.
² Research, Development and Innovation Centre, Tampere University Hospital, Elämänaukio, Kuntokatu 2, 33520 Tampere, Finland.
³ Department of Plastic and Reconstructive Surgery, Tampere University Hospital, Elämänaukio, Kuntokatu 2, 33520 Tampere, Finland.
⁴ Regea Cell and Tissue Center, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland.
⁵ Johan Gadolin Process Chemistry Centre, Åbo Akademi University, Henrikinkatu 2, 20500 Turku, Finland.

Abstract

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.

Keywords: bioactive glass; mesenchymal stem cells; osteogenesis; p38/HSP27 signaling; phosphorylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / physiology
Collagen Type I / metabolism
HSP27 Heat-Shock Proteins / metabolism
Humans
Mesenchymal Stem Cells* / metabolism
Osteogenesis* / physiology

Substances

HSP27 Heat-Shock Proteins
Collagen Type I

Grants and funding

This work was supported by the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, Academy of Finland (Grant No. 326588, 312413 and 336666 to S.M.), Finnish Cultural Foundation (Grant No. 00190350, 00220359 to L.H.(Laura Hyväri)), The Finnish Concordia Fund (Grant No. 20200028 to L.H.(Laura Hyväri)), Alfred Kordelin Foundation (Grant No. 200198 to L.H.(Laura Hyväri)), City of Tampere science grant committee (L.H.(Laura Hyväri)), and the Tampere University Graduate School for Medicine and Life Sciences (L.H.(Laura Hyväri)).