YAMATO Masayuki
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Diverse functions of secreted frizzled-related proteins in the osteoblastogenesis of human multipotent mesenchymal stromal cells.
Journal Formal name：Biomaterials
Abbreviation：Biomaterials
ISSN code：(1878-5905)0142-9612(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 34(13),pp.3270-3278
Author and coauthor Yamada Azusa†, Iwata Takanori*, Yamato Masayuki, Okano Teruo, Izumi Yuichi
Publication date 2013/04
Summary 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.
DOI 10.1016/j.biomaterials.2013.01.066
PMID 23384792