Journal of Oral Tissue Engineering

Modulation of Matrix Mineralization by von Willebrand Factor C Domain Containing 2 in Vivo and in Vitro

Tomoki KANEMARU1, Yoshio OHYAMA1,2, Kazuhiro AOKI3, Atsushi TAMURA4, Nobuhiko YUI4, Satoshi YAMAGUCHI1, and Yoshiyuki MOCHIDA5

1 Department of Maxillofacial Surgery, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
2 Department of Oral and Maxillofacial Surgery, Shizuoka city Shizuoka Hospital, Shizuoka, Japan
3 Department of Basic Oral Health Engineering, Graduate School of Medical and Dental Sciences,
4 Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
5 Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, United States of America

J Oral Tissue Engin 2018; 15(3): 131-142.

Cysteine knot proteins (CKPs) with cysteine-rich domain mainly inhibit bone formation induced by Bone morphogenetic protein (BMP). We identified a novel CKP, von Willebrand factor C domain containing 2 (VWC2), and investigated the effect of VWC2 on bone formation. When VWC2 was added to MC3T3-E1 osteoblastic cell culture, the extent of matrix mineralization and alkaline phos-phatase activity were significantly increased. The newly formed bone area was increased and mineral apposition rate was enhanced by VWC2 when applied to mouse cranial bone defect in vivo. VWC2 addition also increased the expression of key osteogenic markers Osterix and Runt-related transcription factor 2 (Runx2) in primary osteoblast cells. In conclusion, VWC2 positively regulates bone forma-tion possibly through Osterix and Runx2 upregulation.

Key words: VWC2, CKPs, growth factor, matrix mineralization, bone formation

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