title: Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells.
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.
authors.affiliation: Department of Surgery, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Mumme
authors.forename: Celeste
authors.initials: C
authors.lastname: Scotti
authors.forename: Adam
authors.initials: A
authors.lastname: Papadimitropoulos
authors.forename: Athanas
authors.initials: A
authors.lastname: Todorov
authors.forename: Waldemar
authors.initials: W
authors.lastname: Hoffmann
authors.forename: Chiara
authors.initials: C
authors.lastname: Bocelli-Tyndall
authors.forename: Marcel
authors.initials: M
authors.lastname: Jakob
authors.forename: David
authors.initials: D
authors.lastname: Wendt
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
mesh_terms: D000328:Adult; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000254:growth & development; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13; D002118:Calcium