T cell subsets differently regulate osteogenic differentiation of human mesenchymal stromal cells in vitro

Francesco Grassi, Luca Cattini, Laura Gambari, Cristina Manferdini, Anna Piacentini, Elena Gabusi, Andrea Facchini, Gina Lisignoli

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalJournal of Tissue Engineering and Regenerative Medicine
Publication statusAccepted/In press - 2013


  • Bone regeneration
  • CD4
  • Mesenchymal stromal cells
  • PCR array
  • T cells

ASJC Scopus subject areas

  • Biomaterials
  • Medicine (miscellaneous)
  • Biomedical Engineering


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