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Wnt/β‐catenin pathway regulates bone morphogenetic protein (BMP2)‐mediated differentiation of dental follicle cells
Author(s) -
Silvério K. G.,
Davidson K. C.,
James R. G.,
Adams A. M.,
Foster B. L.,
Nociti F. H.,
Somerman M. J.,
Moon R. T.
Publication year - 2012
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2011.01433.x
Subject(s) - wnt signaling pathway , bone sialoprotein , bone morphogenetic protein 2 , axin2 , runx2 , cementoblast , bone morphogenetic protein , lrp5 , microbiology and biotechnology , chemistry , osteoblast , dental follicle , catenin , biology , medicine , osteocalcin , signal transduction , alkaline phosphatase , stem cell , cementum , biochemistry , in vitro , pathology , dentin , gene , enzyme
Silvério KG, Davidson KC, James RG, Adams AM, Foster BL, Nociti FH Jr, Somerman MJ, Moon RT. Wnt/β‐catenin pathway regulates bone morphogenetic protein (BMP2)‐mediated differentiation of dental follicle cells. J Periodont Res 2012; 47: 309–319. © 2011 John Wiley & Sons A/S Background and Objective: Bone morphogenetic protein 2 (BMP2)‐induced osteogenic differentiation has been shown to occur through the canonical Wnt/βcatenin pathway, whereas factors promoting canonical Wnt signaling in cementoblasts inhibit cell differentiation and promote cell proliferation in vitro . The aim of this study was to investigate whether putative precursor cells of cementoblasts, dental follicle cells (murine SVF4 cells), when stimulated with BMP2, would exhibit changes in genes/proteins associated with the Wnt/β‐catenin pathway. Material and Methods: SVF4 cells were stimulated with BMP2, and the following assays were carried out: (i) Wnt/β‐catenin pathway activation assessed by western blotting, β‐catenin/transcription factor (TCF) reporter assays and expression of the lymphoid enhancer‐binding factor‐1 ( Lef1 ), transcription factor 7 ( Tcf 7 ), Wnt inhibitor factor 1 ( Wif1 ) and Axin2 ( Axin2 ) genes; and (ii) cementoblast/osteoblast differentiation assessed by mineralization in vitro , and by the mRNA levels of runt‐related transcription factor 2 ( Runx2 ), osterix ( Osx ), alkaline phosphatase ( Alp ), osteocalcin ( Ocn ) and bone sialoprotein ( Bsp ), determined by quantitative PCR after treatment with wingless‐type MMTV integration site family, member 3A (WNT3A) and knockdown of β‐catenin. Results: WNT3A induced β‐catenin nuclear translocation and up‐regulated the transcriptional activity of a canonical Wnt‐responsive reporter, suggesting that the Wnt/β‐catenin pathway functions in SVF4 cells. Activation of Wnt signaling with WNT3A suppressed BMP2‐mediated induction of cementoblast/osteoblast maturation of SVF4 cells. However, β‐catenin knockdown showed that the BMP2‐induced expression of cementoblast/osteoblast differentiation markers requires endogenous β‐catenin. WNT3A down‐regulated transcripts for Runx2 , Alp and Ocn in SVF4 cells compared with untreated cells. In contrast, BMP2 induction of Bsp transcripts occurred independently of Wnt/β‐catenin signaling. Conclusion: These data suggest that stabilization of β‐catenin by WNT3A inhibits BMP2‐mediated induction of cementoblast/osteoblast differentiation in SVF4 cells, although BMP2 requires endogenous Wnt/β‐catenin signaling to promote cell maturation.