Effects of human vascular endothelial growth factor on reparative dentin formation

Zhang,Juan; Liu,Xia; Yu,Weixian; Zhang,Yingli; Shi,Ce; Ni,Shilei; Liu,Qilin; Li,Xiangwei; Sun,Yingjian; Zheng,Changyu; Sun,Hongchen

doi:10.3892/mmr.2015.4608

Effects of human vascular endothelial growth factor on reparative dentin formation

Authors:
- Juan Zhang
- Xia Liu
- Weixian Yu
- Yingli Zhang
- Ce Shi
- Shilei Ni
- Qilin Liu
- Xiangwei Li
- Yingjian Sun
- Changyu Zheng
- Hongchen Sun
View Affiliations

Affiliations: The Key Laboratory of Tooth Development and Bone Remodeling, Jilin Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
Published online on: November 23, 2015 https://doi.org/10.3892/mmr.2015.4608
Pages: 705-712
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It is a challenge for dentists to save dental pulp in patients with pulp disease without resorting to root canal therapy. Formation of tertiary dentin to maintain pulp vitality is a key odontoblast response to dental pulp injury. Vascular endothelial growth factor (VEGF) is the most potent angiogenic and vasculogenic factor involved in tertiary dentin formation. It was hypothesized that VEGF may be used to treat pulp diseases such as pulpitis. To explore this hypothesis, the first step was to assess whether VEGF affects dental pulp cells to promote reparative dentin formation. In the current study, an AdCMV‑hVEGF vector was constructed to deliver hVEGF into dental pulp cells of exfoliated deciduous teeth (hDPCs) in vitro and dental pulp cells in a rat model in vivo. The collected data clearly demonstrated that hVEGF increased alkaline phosphatase and mineralization by enzymatic activity. RT‑qPCR data demonstrated that hVEGF significantly increased the expression levels of genes commonly involved in osteogenesis/odontogenesis. Data from the in vivo assays indicated that hVEGF enhanced pulp cell proliferation and neovascularization, and markedly increased formation of reparative dentin in dental pulp. The in vitro and in vivo data suggest that hVEGF may have potential clinical applications, thus may aid in the development of novel treatment strategies for dental pulpitis.

View Figures

View References

1	Couve E, Osorio R and Schmachtenberg O: Reactionary dentinogenesis and neuroimmune response in dental caries. J Dent Res. 93:788–793. 2014. View Article : Google Scholar : PubMed/NCBI
2	Farges JC, Joffre A and Magloire H: Response of odontoblastic and pulpal cells to carious lesions. C R Seances Soc Biol Fil. 187:582–595. 1992.In French.
3	Bjørndal L and Mjör IA: Pulp-dentin biology in restorative dentistry. Part 4: Dental caries-characteristics of lesions and pulpal reactions. Quintessence Int. 32:717–736. 2001.
4	Tran-Hung L, Laurent P, Camps J and About I: Quantification of angiogenic growth factors released by human dental cells after injury. Arch Oral Biol. 53:9–13. 2008. View Article : Google Scholar
5	Roberts-Clark DJ and Smith AJ: Angiogenic growth factors in human dentine matrix. Arch Oral Biol. 45:1013–1016. 2000. View Article : Google Scholar : PubMed/NCBI
6	Madeddu P: Therapeutic angiogenesis and vasculogenesis for tissue regeneration. Exp Physiol. 90:315–326. 2005. View Article : Google Scholar : PubMed/NCBI
7	Hood JD, Meininger CJ, Ziche M and Granger HJ: VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol. 274:H1054–H1058. 1998.PubMed/NCBI
8	Artese L, Rubini C, Ferrero G, Fioroni M, Santinelli A and Piattelli A: Vascular endothelial growth factor (VEGF) expression in healthy and inflamed human dental pulps. J Endod. 28:20–23. 2002. View Article : Google Scholar : PubMed/NCBI
9	Virtej A, Løes S, Iden O, Bletsa A and Berggreen E: Vascular endothelial growth factors signalling in normal human dental pulp: A study of gene and protein expression. Eur J Oral Sci. 121:92–100. 2013. View Article : Google Scholar : PubMed/NCBI
10	Soden RI, Botero TM, Hanks CT and Nör JE: Angiogenic signaling triggered by cariogenic bacteria in pulp cells. J Dent Res. 88:835–840. 2009. View Article : Google Scholar : PubMed/NCBI
11	Sakai VT, Zhang Z, Dong Z, Neiva KG, Machado MA, Shi S, Santos CF and Nör JE: SHED differentiate into functional odontoblasts and endothelium. J Dent Res. 89:791–796. 2010. View Article : Google Scholar : PubMed/NCBI
12	Matsushita K, Motani R, Sakuta T, Yamaguchi N, Koga T, Matsuo K, Nagaoka S, Abeyama K, Maruyama I and Torii M: The role of vascular endothelial growth factor in human dental pulp cells: Induction of chemotaxis, proliferation and differentiation and activation of the AP-1-dependent signaling pathway. J Dent Res. 79:1596–1603. 2000. View Article : Google Scholar : PubMed/NCBI
13	Huang B, Maciejewska I, Sun Y, Peng T, Qin D, Lu Y, Bonewald L, Butler WT, Feng J and Qin C: Identification of full-length dentin matrix protein 1 in dentin and bone. Calcif Tissue Int. 82:401–410. 2008. View Article : Google Scholar : PubMed/NCBI
14	Baba O, Qin C, Brunn JC, Jones JE, Wygant JN, McIntyre BW and Butler WT: Detection of dentin sialoprotein in rat periodontium. Eur J Oral Sci. 112:163–170. 2004. View Article : Google Scholar : PubMed/NCBI
15	Moses KD, Butler WT and Qin C: Immunohistochemical study of small integrin-binding ligand, N-linked glycoproteins in reactionary dentin of rat molars at different ages. Eur J Oral Sci. 114:216–222. 2006. View Article : Google Scholar : PubMed/NCBI
16	Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG and Shi S: SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA. 100:5807–5812. 2003. View Article : Google Scholar : PubMed/NCBI
17	Nagy JA, Benjamin L, Zeng H, Dvorak AM and Dvorak HF: Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis. 11:109–119. 2008. View Article : Google Scholar : PubMed/NCBI
18	Heyeraas KJ and Berggreen E: Interstitial fluid pressure in normal and inflamed pulp. Crit Rev Oral Biol Med. 10:328–336. 1999. View Article : Google Scholar
19	Botero TM, Shelburne CE, Holland GR, Hanks CT and Nör JE: TLR4 mediates LPS-induced VEGF expression in odontoblasts. J Endod. 32:951–955. 2006. View Article : Google Scholar : PubMed/NCBI
20	Botero TM, Son JS, Vodopyanov D, Hasegawa M, Shelburne CE and Nör JE: MAPK signaling is required for LPS-induced VEGF in pulp stem cells. J Dent Res. 89:264–269. 2010. View Article : Google Scholar : PubMed/NCBI
21	Mangano C, Paino F, d'Aquino R, De Rosa A, Iezzi G, Piattelli A, Laino L, Mitsiadis T, Desiderio V, Mangano F, et al: Human dental pulp stem cells hook into biocoral scaffold forming an engineered biocomplex. PLoS One. 6:e187212011. View Article : Google Scholar : PubMed/NCBI
22	Feng JQ, Luan X, Wallace J, Jing D, Ohshima T, Kulkarni AB, D'Souza RN, Kozak CA and MacDougall M: Genomic orga-nization, chromosomal mapping and promoter analysis of the mouse dentin sialophosphoprotein (Dspp) gene, which codes for both dentin sialoprotein and dentin phosphoprotein. J Biol Chem. 273:9457–9464. 1998. View Article : Google Scholar : PubMed/NCBI
23	MacDougall M, Gu TT and Simmons D: Dentin matrix protein-1, a candidate gene for dentinogenesis imperfecta. Connect Tissue Res. 35:267–272. 1996. View Article : Google Scholar : PubMed/NCBI
24	Suzuki S, Sreenath T, Haruyama N, Honeycutt C, Terse A, Cho A, Kohler T, Müller R, Goldberg M and Kulkarni AB: Dentin sialo-protein and dentin phosphoprotein have distinct roles in dentin mineralization. Matrix Biol. 28:221–229. 2009. View Article : Google Scholar : PubMed/NCBI
25	Mitsiadis TA and Rahiotis C: Parallels between tooth development and repair: Conserved molecular mechanisms following carious and dental injury. J Dent Res. 83:896–902. 2004. View Article : Google Scholar : PubMed/NCBI
26	Huang GT: Pulp and dentin tissue engineering and regeneration: Current progress. Regen Med. 4:697–707. 2009. View Article : Google Scholar : PubMed/NCBI
27	Jin H, Thomas HF and Chen J: Wound healing and revascularization: A histologic observation of experimental tooth root fracture. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 81:26–30. 1996. View Article : Google Scholar : PubMed/NCBI
28	Kanematsu A, Yamamoto S, Ozeki M, Noguchi T, Kanatani I, Ogawa O and Tabata Y: Collagenous matrices as release carriers of exogenous growth factors. Biomaterials. 25:4513–4520. 2004. View Article : Google Scholar : PubMed/NCBI
29	Peters MC, Polverini PJ and Mooney DJ: Engineering vascular networks in porous polymer matrices. J Biomed Mater Res. 60:668–678. 2002. View Article : Google Scholar : PubMed/NCBI
30	Sun Q, Chen RR, Shen Y, Mooney DJ, Rajagopalan S and Grossman PM: Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb. Pharm Res. 22:1110–1116. 2005. View Article : Google Scholar : PubMed/NCBI
31	Mullane EM, Dong Z, Sedgley CM, Hu JC, Botero TM, Holland GR and Nör JE: Effects of VEGF and FGF2 on the revascularization of severed human dental pulps. J Dent Res. 87:1144–1148. 2008. View Article : Google Scholar : PubMed/NCBI