Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts

Abstract Soft tissue calcification occurs in many parts of the body, including the gingival tissue. Epithelial cell-derived MVs can control many functions in fibroblasts but their role in regulating mineralization has not been explored. We hypothesized that microvesicles (MVs) derived from gingival...

Full description

Bibliographic Details
Main Authors: Shuichiro Kobayashi, Jiarui Bi, Gethin Owen, Nelli Larjava, Leeni Koivisto, Lari Häkkinen, Hannu Larjava
Format: Article
Language:English
Published: Nature Portfolio 2022-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-19732-1
_version_ 1811208829915889664
author Shuichiro Kobayashi
Jiarui Bi
Gethin Owen
Nelli Larjava
Leeni Koivisto
Lari Häkkinen
Hannu Larjava
author_facet Shuichiro Kobayashi
Jiarui Bi
Gethin Owen
Nelli Larjava
Leeni Koivisto
Lari Häkkinen
Hannu Larjava
author_sort Shuichiro Kobayashi
collection DOAJ
description Abstract Soft tissue calcification occurs in many parts of the body, including the gingival tissue. Epithelial cell-derived MVs can control many functions in fibroblasts but their role in regulating mineralization has not been explored. We hypothesized that microvesicles (MVs) derived from gingival epithelial cells could regulate calcification of gingival fibroblast cultures in osteogenic environment. Human gingival fibroblasts (HGFs) were cultured in osteogenic differentiation medium with or without human gingival epithelial cell-derived MV stimulation. Mineralization of the cultures, localization of the MVs and mineral deposits in the HGF cultures were assessed. Gene expression changes associated with MV exposure were analyzed using gene expression profiling and real-time qPCR. Within a week of exposure, epithelial MVs stimulated robust mineralization of HGF cultures that was further enhanced by four weeks. The MVs taken up by the HGF's did not calcify themselves but induced intracellular accumulation of minerals. HGF gene expression profiling after short exposure to MVs demonstrated relative dominance of inflammation-related genes that showed increases in gene expression. In later cultures, OSX, BSP and MMPs were significantly upregulated by the MVs. These results suggest for the first time that epithelial cells maybe associated with the ectopic mineralization process often observed in the soft tissues.
first_indexed 2024-04-12T04:28:19Z
format Article
id doaj.art-d131ccc65e7446a497c70e5dbea6fea6
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-04-12T04:28:19Z
publishDate 2022-09-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-d131ccc65e7446a497c70e5dbea6fea62022-12-22T03:48:00ZengNature PortfolioScientific Reports2045-23222022-09-0112111410.1038/s41598-022-19732-1Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblastsShuichiro Kobayashi0Jiarui Bi1Gethin Owen2Nelli Larjava3Leeni Koivisto4Lari Häkkinen5Hannu Larjava6Faculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaFaculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaFaculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaFaculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaFaculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaFaculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaFaculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British ColumbiaAbstract Soft tissue calcification occurs in many parts of the body, including the gingival tissue. Epithelial cell-derived MVs can control many functions in fibroblasts but their role in regulating mineralization has not been explored. We hypothesized that microvesicles (MVs) derived from gingival epithelial cells could regulate calcification of gingival fibroblast cultures in osteogenic environment. Human gingival fibroblasts (HGFs) were cultured in osteogenic differentiation medium with or without human gingival epithelial cell-derived MV stimulation. Mineralization of the cultures, localization of the MVs and mineral deposits in the HGF cultures were assessed. Gene expression changes associated with MV exposure were analyzed using gene expression profiling and real-time qPCR. Within a week of exposure, epithelial MVs stimulated robust mineralization of HGF cultures that was further enhanced by four weeks. The MVs taken up by the HGF's did not calcify themselves but induced intracellular accumulation of minerals. HGF gene expression profiling after short exposure to MVs demonstrated relative dominance of inflammation-related genes that showed increases in gene expression. In later cultures, OSX, BSP and MMPs were significantly upregulated by the MVs. These results suggest for the first time that epithelial cells maybe associated with the ectopic mineralization process often observed in the soft tissues.https://doi.org/10.1038/s41598-022-19732-1
spellingShingle Shuichiro Kobayashi
Jiarui Bi
Gethin Owen
Nelli Larjava
Leeni Koivisto
Lari Häkkinen
Hannu Larjava
Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts
Scientific Reports
title Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts
title_full Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts
title_fullStr Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts
title_full_unstemmed Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts
title_short Gingival epithelial cell-derived microvesicles activate mineralization in gingival fibroblasts
title_sort gingival epithelial cell derived microvesicles activate mineralization in gingival fibroblasts
url https://doi.org/10.1038/s41598-022-19732-1
work_keys_str_mv AT shuichirokobayashi gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts
AT jiaruibi gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts
AT gethinowen gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts
AT nellilarjava gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts
AT leenikoivisto gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts
AT larihakkinen gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts
AT hannularjava gingivalepithelialcellderivedmicrovesiclesactivatemineralizationingingivalfibroblasts