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Int. J. Mol. Sci. 2017, 18(11), 2380; https://doi.org/10.3390/ijms18112380

Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts

1
Department of Molecular Genetics, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul 08826, Korea
2
Department of Pharmacology & Dental Therapeutics, School of Dentistry, Seoul National University, Seoul 08826, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 October 2017 / Revised: 6 November 2017 / Accepted: 7 November 2017 / Published: 9 November 2017
(This article belongs to the Section Materials Science)
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Abstract

Cementum is a mineralized layer on the tooth’s root surface and facilitates the biomechanical anchoring of fibrous connective tissues as a part of tooth-supportive complexes. Previously, we observed that OCCM30 cementoblasts cultured on fibrin matrices underwent apoptosis due to fibrin degradation through the expression of proteases. Here, we demonstrated that OCCM30 on fibrin matrices (OCCM30-fibrin) enhanced canonical Wnt signaling, which directed to plasminogen expression. The OCCM30-fibrin showed higher levels of Wnt3a expression, nuclear translocation of β-catenin, and T-cell factor (TCF) optimal motif (TOP) reporter activity than the cells on tissue culture dishes (OCCM30-TCD), indicating that the OCCM30-fibrin enhanced canonical Wnt/β-catenin signaling. Also, OCCM30-fibrin expressed biomineralization-associated markers at higher levels than OCCM30-TCD, of which levels were further increased with LiCl, a Wnt signaling activator. The OCCM30 cementoblasts simultaneously showed that high levels of plasminogen, a critical component of fibrinolysis, were expressed in the OCCM30-fibrin. Activation of canonical Wnt signaling with LiCl treatment or with forced lymphoid enhancer factor 1 (LEF1)-expression increased the expression of plasminogen. On the contrary, the inhibition of canonical Wnt signaling with siRNAs against Wnt3a or β-catenin abrogated fibrin-enhanced plasminogen expression. Furthermore, there are three conserved putative response elements for the LEF1/β-catenin complex in the plasminogen proximal promoter regions (−900 to +54). Site-directed mutations and chromatin immunoprecipitation indicated that canonical Wnt signaling directed plasminogen expression. Taken together, this study suggests that fibrin-based materials can modulate functional periodontal formations in controlling cementoblast differentiation and fibrin degradation. View Full-Text
Keywords: fibrin; cementoblast; plasminogen; Wnt3a; β-catenin fibrin; cementoblast; plasminogen; Wnt3a; β-catenin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Rahman, S.U.; Park, C.H.; Baek, J.-H.; Ryoo, H.-M.; Woo, K.M. Fibrin-Enhanced Canonical Wnt Signaling Directs Plasminogen Expression in Cementoblasts. Int. J. Mol. Sci. 2017, 18, 2380.

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