title: Human osteoblast-derived factors induce early osteogenic markers in human mesenchymal stem cells.
abstract: The capacity of human mesenchymal stem cells (hMSC) for self-renewal and differentiation is a tightly regulated process within their microenvironment--the stem cell niche. For future therapeutic applications of hMSC within the frame of tissue engineering, it is of major importance to understand the factors involved in triggering differentiation cascades of hMSC. Using either osteoblast-conditioned medium or an indirect coculture system, we investigated whether soluble factors from human osteoblasts (hOB) are sufficient to induce early osteogenic markers in hMSC. Thereby, we detected an induction of several osteogenic markers like alkaline phosphatase, bone sialoprotein 2, leptin receptor, decorin, and cathepsin K in hMSC as indicators of the onset of early osteogenesis. Further, because Wnt signaling has been reported to play an important role in osteogenesis, we performed RNAi against the main Wnt mediator beta-catenin and the low-density lipoprotein receptor-related protein 5 as a major Wnt co-receptor in hMSC. Whereas alkaline phosphatase was significantly downregulated with this approach, the other osteogenic markers showed a markedly upregulation. These observations suggest that hOB-secreted factors could induce early osteogenic markers in hMSC. Thus, with regard to a therapeutic setting, these findings may pave the way for a more in vivo-related differentiation procedure for the generation of osteoblast-like cells.
authors.affiliation: Division of Clinical Chemistry and Clinical Biochemistry, Department of Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ilmer
authors.forename: Marisa
authors.initials: M
authors.lastname: Karow
authors.forename: Claudia
authors.initials: C
authors.lastname: Geissler
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Peter
authors.initials: P
authors.lastname: Neth
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013194:Staining and Labeling; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D015415:Biomarkers; D017077:Culture Media, Conditioned; D051153:Wnt Proteins; C010078:alizarin