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CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model
Raffaella Giancola1, Francesco Oliva2,3, Marialucia Gallorini4
1Department of Haematology, Transfusion Medicine and Biotechnologies, Cytofluorimetry and Cell Sorting Service, Ospedale Spirito Santo, 65122 Pescara, Italy.
Abstract:
Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs.
Insights
Tumor necrosis factor-alpha (TNFα) and interferon-gamma (IFNγ) alter rotator cuff tendon stem cell (TCSC) populations and upregulate CD200. These findings suggest CD200 may regulate inflammation in tendon injuries.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Musculoskeletal Research
Background:
- Rotator cuff tendon (RCT) disease involves inflammation, with pro-inflammatory cytokines and tendon stem/progenitor cells (TSPCs) playing key roles.
- The precise molecular mechanisms underlying RCT inflammation remain incompletely understood.
Purpose of the Study:
- To investigate the effects of pro-inflammatory cytokines on rotator cuff tendon stem/progenitor cells (TSPCs).
- To identify molecular players involved in the inflammatory response within TSPCs.
Main Methods:
- Flow cytometry was used to analyze subpopulations of TSPCs after TNFα and/or IFNγ administration.
- Protein expression of STAT1, STAT3, and MMP9 was assessed.
- Gene expression of IRF1, CAAT, DOK2, NF-κb, TGFBR2, and RAS-GAP was analyzed.
Main Results:
- TNFα alone or with IFNγ decreased CD146+CD49d+ and CD146+CD49f+ TSPCs but not CD146+CD109+ TSPCs.
- Pro-inflammatory cytokines upregulated CD200 expression in CD146+ TSPCs.
- The TNFα/IFNγ combination modulated STAT1, STAT3, MMP9, IRF1, CAAT, and DOK2 expression.
Conclusions:
- CD200 may have a significant role in regulating inflammation associated with tendon injuries.
- Specific genes like IRF1, CAAT, and DOK2 could be novel contributors to TSPC inflammatory responses.
