%0 Journal Article
%T Interleukin-1¦Â modulates endochondral ossification by human adult bone marrow stromal cells
%A M Mumme
%A C Scotti
%A A Papadimitropoulos
%A A Todorov
%J European Cells and Materials (ECM)
%D 2012
%I 
%X Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1¦Â (IL-1¦Â) 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¦Â (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¦Â enhanced calcium deposition (62.2-fold) and BMP-2 mRNA expression by differential activation of NF-¦ÊB and ERK signalling. IL-1¦Â-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¦Â 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.
%K Mesenchymal stem cells
%K tissue engineering
%K chondrogenesis
%K osteogenesis
%K endochondral ossification
%U http://www.ecmjournal.org/journal/papers/vol024/pdf/v024a16.pdf