Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation

Summary Objective The effects of inflammation on bone development from mesenchymal stem cells (MSC) are unclear due to the difficulty in isolating MSC. The aim of this study was to develop a MSC isolation method and to determine the in vitro effects of interleukin-1β (IL-1β) and tumor necrosis facto...

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Bibliographic Details
Published in:	Osteoarthritis and cartilage Vol. 17; no. 6; pp. 735 - 742
Main Authors:	Lacey, D.C, Simmons, P.J, Graves, S.E, Hamilton, J.A
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-06-2009
Subjects:	Animals Cell Differentiation - drug effects Cells, Cultured IL-1 Interleukin-1beta - genetics Interleukin-1beta - metabolism Mesenchymal stem cells Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - metabolism Mice Osteoblasts and differentiation Osteogenesis - drug effects Osteogenesis - genetics Osteonectin - drug effects Osteonectin - genetics Osteopontin - drug effects Osteopontin - genetics Rheumatology TNF Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism IL-1 TNF Mesenchymal stem cells Osteoblasts and differentiation
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Summary:	Summary Objective The effects of inflammation on bone development from mesenchymal stem cells (MSC) are unclear due to the difficulty in isolating MSC. The aim of this study was to develop a MSC isolation method and to determine the in vitro effects of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) on their osteogenic differentiation. Methods Murine MSC were isolated from the limbs of C57/Bl6 mice through collagenase digestion of bone and enriched as the Stem cell antigen (Sca-1)+ CD31− CD45− population, using lineage immunodepletion, followed by fluorescence-activated cell sorting (FACS). They were differentiated along the osteoblast linage in the presence or absence of IL-1β and TNFα. Mineralization was measured as was the expression of a number of osteogenic genes by quantitative polymerase chain reaction (PCR). Results We show that osteogenic differentiation from the MSC population is suppressed by IL-1β and TNFα. In addition to suppression of bone mineralization, both cytokines inhibited the differentiation-associated increases in alkaline phosphatase (ALP) activity and the gene expression for ALP, α1(I) procollagen, runt-related transcription factor 2 (Runx2) and osterix. However, only TNFα inhibited osteonectin and osteopontin mRNA expression and only IL-1β reduced cell proliferation. Conclusions The convenient isolation technique enables the easy generation of sufficient MSC to permit the molecular analysis of their differentiation. We were thus able to show that the proinflammatory cytokines, IL-1β and TNFα, can compromise bone development from this primary MSC population, although with some significant differences. The potential involvement of specific inflammatory mediators needs to be taken into account if optimal bone repair and presumably that of other tissues are to be achieved with MSC.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1063-4584 1522-9653
DOI:	10.1016/j.joca.2008.11.011