期刊
EUROPEAN CELLS & MATERIALS
卷 24, 期 -, 页码 224-236出版社
AO RESEARCH INSTITUTE DAVOS-ARI
DOI: 10.22203/eCM.v024a16
关键词
Mesenchymal stem cells; tissue engineering; chondrogenesis; osteogenesis; endochondral ossification
资金
- European Union (OPHIS) [FP7-NMP-2009-SMALL-3-246373]
- Swiss National Foundation [NMS1725]
Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1 beta (IL-1 beta) 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-1 beta (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-1 beta enhanced calcium deposition (62.2-fold) and BMP-2 mRNA expression by differential activation of NF-kappa B and ERK signalling. IL-1 beta-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-1 beta 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.
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