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

Marcus Mumme, Celeste Scotti, Adam Papadimitropoulos, Athanas Todorov, Waldemar Hoffmann, Chiara Bocelli-Tyndall, Marcel Jakob, David Wendt, Ivan Martin, Andrea Barbero

Research output: Contribution to journalArticle

Abstract

Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1β (IL-1β) 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-1β (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-1β enhanced calcium deposition (62.2-fold) and BMP-2 mRNA expression by differential activation of NF-κB and ERK signalling. IL-1β-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-1β 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.

Original languageEnglish
Pages (from-to)224-236
Number of pages13
JournalEuropean Cells and Materials
Volume24
Publication statusPublished - Jul 2012

Keywords

  • Chondrogenesis
  • Endochondral ossification
  • Mesenchymal stem cells
  • Osteogenesis
  • Tissue engineering

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Bioengineering
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

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  • Cite this

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