Interleukin-1beta modulates endochondral ossification by human adult bone marrow stromal cells

Mumme, M. and Scotti, C. and Papadimitropoulos, A. and Todorov, A. and Hoffmann, W. and Bocelli-Tyndall, C. and Jakob, M. and Wendt, D. and Martin, I. and Barbero, A.. (2012) Interleukin-1beta modulates endochondral ossification by human adult bone marrow stromal cells. European cells & materials, Vol. 24. pp. 224-236.

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Official URL: http://edoc.unibas.ch/dok/A6338301

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Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1beta (IL-1beta) on the main events of endochondral bone formation by human bone marrow mesenchymal stromal cells (BM-MSC), namely cell proliferation, differentiation and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of IL-1beta (50 pg/mL) enhanced colony-forming units-fibroblastic (CFU-f) and -osteoblastic (CFU-o) number (up to 1.5-fold) and size (1.2-fold) in the absence of further supplements and glycosaminoglycan accumulation (1.4-fold) upon BM-MSC chondrogenic induction. In osteogenically cultured BM-MSC, IL-1beta enhanced calcium deposition (62.2-fold) and BMP-2 mRNA expression by differential activation of NF-kappaB and ERK signalling. IL-1beta-treatment of BM-MSC generated cartilage resulted in higher production of MMP-13 (14.0-fold) in vitro, mirrored by an increased accumulation of the cryptic cleaved fragment of aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas), resulting in the formation of mature bone and bone marrow after 12 weeks. In conclusion, IL-1beta finely modulates early and late events of the endochondral bone formation by BM-MSC. Controlling the inflammatory environment could enhance the success of therapeutic approaches for the treatment of fractures by resident MSC and as well as improve the engineering of implantable tissues.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Tissue Engineering (Martin)
UniBasel Contributors:Martin, Ivan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Univ. of Wales
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:12
Deposited On:10 Apr 2015 09:12

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