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

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.