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FGF2 induces RANKL gene expression as well as IL1beta regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells

Bocelli-Tyndall, C. and Trella, E. and Frachet, A. and Zajac, P. and Pfaff, D. and Geurts, J. and Heiler, S. and Barbero, A. and Mumme, M. and Resink, T. J. and Schaeren, S. and Spagnoli, G. C. and Tyndall, A.. (2015) FGF2 induces RANKL gene expression as well as IL1beta regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells. Annals of the rheumatic diseases, Vol. 74, H. 1. pp. 260-266.

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Official URL: http://edoc.unibas.ch/dok/A6223363

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Abstract

OBJECTIVE: Human bone marrow mesenchymal stromal cells (hBM-MSC) are being applied in tissue regeneration and treatment of autoimmune diseases (AD). Their cellular and immunophenotype depend on isolation and culture conditions which may influence their therapeutic application and reflect their in vivo biological functions. We have further characterised the phenotype induced by fibroblast growth factor 2 (FGF2) on healthy donor hBM-MSC focusing on the osteoimmunological markers osteoprotegerin (OPG), receptor activator of nuclear factor kB (RANK), RANK ligand (RANKL) and HLA-DR and their regulation of expression by the inflammatory cytokines IL1beta and IFNgamma. METHODS: RANK, RANKL, OPG and HLA-DR expression in hBM-MSC expanded under specific culture conditions, were measured by RT-PCR and flow cytometry. MAPKs induction by FGF2, IL1beta and IFNgamma in hBM-MSC was analysed by immunoblotting and RT-PCR. RESULTS: In hBM-MSC, OPG expression is constitutive and FGF2 independent. RANKL expression depends on FGF2 and ERK1/2 activation. IL1beta and IFNgamma activate ERK1/2 but fail to induce RANKL. Only IL1beta induces P38MAPK. The previously described HLA-DR induced by FGF2 through ERK1/2 on hBM-MSC, is suppressed by IL1beta through inhibition of CIITA transcription. HLA-DR induced by IFNgamma is not affected by IL1beta in hBM-MSC, but is suppressed in articular chondrocytes and lung fibroblasts. CONCLUSIONS: RANKL expression and IL1beta regulated MHC-class II, both induced via activation of the ERK1/2 signalling pathway, are specific for progenitor hBM-MSC expanded in the presence of FGF2. HLA-DR regulated by IL1beta and ERK1/2 is observed on hBM-MSC during early expansion without FGF2 suggesting previous in vivo acquisition. Stromal progenitor cells with this phenotype could have an osteoimmunological role during bone regeneration.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Oncology Surgery (Spagnoli)
03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Ehemalige Einheiten Operative Fächer (Klinik) > Orthopädie (Valderrabano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Ehemalige Einheiten Operative Fächer (Klinik) > Orthopädie (Valderrabano)
UniBasel Contributors:Geurts, Jeroen and Spagnoli, Giulio C. and Resink, Thérèse J.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:British Medical Association
ISSN:0003-4967
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:59
Deposited On:06 Feb 2015 09:59

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