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T cell subsets differently regulate osteogenic differentiation of human mesenchymal stromal cells in vitro
Author(s) -
Grassi Francesco,
Cattini Luca,
Gambari Laura,
Manferdini Cristina,
Piacentini Anna,
Gabusi Elena,
Facchini Andrea,
Lisignoli Gina
Publication year - 2016
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.1727
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , stromal cell , osteocalcin , bone sialoprotein , chemistry , cd8 , alkaline phosphatase , cellular differentiation , runx2 , in vitro , immunology , osteoblast , biology , immune system , cancer research , gene , biochemistry , enzyme
T lymphocytes play a key role in the regulation of bone homeostasis and bone healing. The inflammatory response at the site of bone injury is essential to the initiation of the bone repair program; however, an uncontrolled exposure to inflammatory environment has a negative effect on tissue regeneration – indeed, activated T cells were shown to inhibit osteogenic differentiation on human mesenchymal stromal cells (MSCs). Whether resting T cells can induce osteogenic differentiation of MSCs and what role specific T cells subset play in this process is still elusive. In this study, we sought to analyse the osteogenic gene expression profile of whole T cells, CD4 and CD8 T cells isolated from healthy donors and investigated whether secreted factors from each group modulate osteogenic differentiation of human MSCs. Gene expression profiling identified a pool of 51 genes involved at various stages in bone growth which are expressed above detectable levels in CD4 and CD8 T cells. Most genes of this pool were expressed at higher levels in the CD4 subset. In vitro mineralization assays revealed that conditioned medium from CD4 T cells, but not from CD8 cells, significantly increased mineralization in osteogenic cultures of human MSCs; furthermore, mRNA expression of Runt‐related transcription factor 2 ( RUNX‐2 ), osteocalcin ( OC ), bone sialoprotein ( BSP ) and alkaline phosphatase ( ALP ) in MSCs was significantly upregulated in the presence of CD4‐conditioned medium but not with that obtained from CD8. The results show a differential role for CD4 and CD8 T cells in supporting bone formation and identify an osteogenic gene signature of each subset. Copyright © 2013 John Wiley & Sons, Ltd.