title: Diverse functions of secreted frizzled-related proteins in the osteoblastogenesis of human multipotent mesenchymal stromal cells.
abstract: Osteoinductive pretreatment of human mesenchymal stromal cells (hMSCs) has been widely accepted in bone tissue engineering before the use of cell transplantation; however, the mechanisms by which osteoinductive medium (OIM) enhances osteoblastic differentiation are not well understood. Using periodontal ligament-derived hMSCs, we identified key signalling molecules for osteoblastogenesis. Alkaline phosphatase activity induced by OIM, which contains ascorbic acid, β-glycerophosphate, and dexamethasone, was decreased by XAV939, which is an inhibitor of canonical WNT signalling, in a dose-dependent manner. A quantitative RT-PCR array demonstrated the upregulation of secreted frizzled-related protein (SFRP) 3 and the downregulation of SFRP4 during osteoinduction. Functional studies showed that SFRP3 promoted and SFRP4 suppressed the osteoblastic differentiation of hMSCs. In addition, SFRP3 inhibited non-canonical WNT signalling by binding WNT5A, which is a representative non-canonical WNT protein. These results indicate the involvement of the WNT signalling pathway during the osteoblastic differentiation of hMSCs. SFRPs oppositely control osteoblastogenesis through canonical and non-canonical pathways and may be useful for directing the lineage of hMSCs in cytotherapeutic use.
authors: Department of Periodontology, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Azusa
authors: A
authors: Yamada
authors: Takanori
authors: T
authors: Iwata
authors: Masayuki
authors: M
authors: Yamato
authors: Teruo
authors: T
authors: Okano
authors: Yuichi
authors: Y
authors: Izumi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D005434:Flow Cytometry; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics
chemical_list: D003470:Culture Media; D051157:Frizzled Receptors; D006575:Heterocyclic Compounds, 3-Ring; D034741:RNA, Small Interfering; D051153:Wnt Proteins; C544261:XAV939