YAMATO Masayuki
   Department   Graduate School of Medical Science, Graduate School of Medical Science
   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