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Proinflammatory T cells and IL-17 stimulate osteoblast differentiation
Michiel Croes1, F Cumhur Öner1, Danihel van Neerven1
1Department of Orthopedics, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.
Bone
|January 19, 2016
Summary
Proinflammatory T cells, particularly T helper 17 cells, enhance bone regeneration by stimulating human mesenchymal stem cells (MSCs). Their secreted factors, like IL-17A, promote osteogenic differentiation and matrix mineralization.
Area of Science:
- Immunology
- Regenerative Medicine
- Cell Biology
Background:
- Local immune responses influence bone regeneration.
- T lymphocytes and cytokines regulate fracture healing.
- Direct effects of T cells on bone progenitor cells remain unclear.
Purpose of the Study:
- Investigate T cell subsets' role in osteogenic differentiation of human mesenchymal stem cells (MSCs).
- Examine the impact of T cell-secreted factors on MSC osteogenesis.
- Determine the influence of different T cell phenotypes on bone regeneration.
Main Methods:
- In vitro study using human mesenchymal stem cells (MSCs).
- Exposure of MSCs to activated T cells and their conditioned media.
- Blocking specific cytokines (IFN-γ, TGF-β) and analyzing T cell subsets (T helper 17, regulatory T cells).
- Assessing alkaline phosphatase activity, matrix mineralization, and osteogenic marker expression.
Main Results:
- Activated T cells and their factors significantly increased MSC alkaline phosphatase activity and matrix mineralization.
- Blocking IFN-γ abolished the pro-osteogenic effect; blocking TGF-β enhanced it.
- T helper 17 cells and their cytokines (IL-17A, IL-17F) strongly upregulated osteogenic markers in MSCs.
- IL-17A showed synergistic effects with bone morphogenetic protein 2.
Conclusions:
- Activated T cell subsets differentially affect osteoblast maturation via soluble factors.
- Proinflammatory T cells, especially T helper 17 cells, are potent stimulators of osteogenesis.
- Targeting specific T cell subsets or their cytokines may improve bone regeneration strategies.
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