Abstract
Dentin is a permeable and complex tubular composite formed by the mineralization of predentin that mineralization and repair are of considerable clinical interest during dentin homeostasis. The role of Vdr, a receptor of vitamin D, in dentin homeostasis remains unexplored. The aim of the present study was to assess the impact of Vdr on predentin mineralization and dental repair. Vdr-knockout (Vdr−/−) mice models were constructed; histology and immunohistochemistry analyses were conducted for both WT and Vdr−/− mice. The finding revealed a thicker predentin in Vdr−/− mice, characterized by higher expression of biglycan and decorin. A dental injury model was employed to observe tertiary dentin formation in Vdr−/− mice with dental injuries. Results showed that tertiary dentin was harder to form in Vdr−/− mice with dental injury. Over time, heightened pulp invasion was observed at the injury site in Vdr−/− mice. Expression of biglycan and decorin was reduced in the predentin at the injury site in the Vdr−/− mice by immunohistochemistry. Taken together, our results imply that Vdr plays a regulatory role in predentin mineralization and tertiary dentin formation during dentin homeostasis.
Similar content being viewed by others
Data Availability
The data used to support the findings of this study were included within the article.
References
Aguiar MC, Arana-Chavez VE (2007) Ultrastructural and immunocytochemical analyses of osteopontin in reactionary and reparative dentine formed after extrusion of upper rat incisors. J Anat 210:418–427
Alania Y, Creighton J, Trevelin LT, Zamperini CA, Bedran-Russo AK (2020) Regional contribution of proteoglycans to the fracture toughness of the dentin extracellular matrix. J Biomech 101:109633
Aryal YP, Yeon CY, Kim TY, Lee ES, Sung S, Pokharel E, Kim JY, Choi SY, Yamamoto H, Sohn WJ, Lee Y, An SY, An CH, Jung JK, Ha JH, Kim JY (2021) Facilitating reparative dentin formation using apigenin local delivery in the exposed pulp cavity. Front Physiol 12:773878
Baranova J, Buchner D, Gotz W, Schulze M, Tobiasch E (2020) Tooth formation: are the hardest tissues of human body hard to regenerate? Int J Mol Sci 21:4031
Choi H, Kim TH, Jeong JK, Strandgren C, Eriksson M, Cho ES (2018) Expression of the Hutchinson-Gilford progeria mutation leads to aberrant dentin formation. Sci Rep 8:15368
Choung HW, Lee DS, Lee JH, Shon WJ, Lee JH, Ku Y, Park JC (2016) Tertiary dentin formation after indirect pulp capping using protein CPNE7. J Dent Res 95:906–912
DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689S-1696S
Embery G, Hall R, Waddington R, Septier D, Goldberg M (2001) Proteoglycans in dentinogenesis. Crit Rev Oral Biol Med 12:331–349
Engstrom C, Linde A, Magnusson BC (1977) Odontoblast metabolism in rats deficient in vitamin D and calcium I: a histochemical survey. J Oral Pathol 6:359–366
Figueiredo Macedo de Lima J, Aguiar Jordao Mainardi MDC, Puppin-Rontani RM, Pereira Rodrigues-Filho U, Suzy Liporoni PC, Calegaro ML, Rischka K, Baggio Aguiar FH (2020) Bioinspired catechol chemistry for dentin remineralization: a new approach for the treatment of dentin hypersensitivity. Dent Mater 36:501–511
Goldberg M, Septier D, Rapoport O, Iozzo RV, Young MF, Ameye LG (2005) Targeted disruption of two small leucine-rich proteoglycans, biglycan and decorin, excerpts divergent effects on enamel and dentin formation. Calcif Tissue Int 77:297–310
Grawish ME, Grawish LM, Grawish HM, Grawish MM, Holiel AA, Sultan N, El-Negoly SA (2022) Demineralized dentin matrix for dental and alveolar bone tissues regeneration: an innovative scope review. Tissue Eng Regen Med 19:687–701
Han B, Li Q, Wang C, Chandrasekaran P, Zhou Y, Qin L, Liu XS, Enomoto-Iwamoto M, Kong D, Iozzo RV, Birk DE, Han L (2021) Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis. Osteoarthritis Cartilage 29:1181–1192
Haruyama N, Sreenath TL, Suzuki S, Yao X, Wang Z, Wang Y, Honeycutt C, Iozzo RV, Young MF, Kulkarni AB (2009) Genetic evidence for key roles of decorin and biglycan in dentin mineralization. Matrix Biol 28:129–136
Iozzo RV (1999) The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem 274:18843–18846
Irfan M, Kim JH, Marzban H, Reed DA, George A, Cooper LF, Chung S (2022) The role of complement C5a receptor in DPSC odontoblastic differentiation and in vivo reparative dentin formation. Int J Oral Sci 14:7
Kim MS, Fujiki R, Kitagawa H, Kato S (2007a) 1alpha,25(OH)2D3-induced DNA methylation suppresses the human CYP27B1 gene. Mol Cell Endocrinol 265–266:168–173
Kim MS, Fujiki R, Murayama A, Kitagawa H, Yamaoka K, Yamamoto Y, Mihara M, Takeyama K, Kato S (2007b) 1Alpha,25(OH)2D3-induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter. Mol Endocrinol 21:334–342
Kinoshita M, Yamada S, Sasaki J, Suzuki S, Kajikawa T, Iwayama T, Fujihara C, Imazato S, Murakami S (2023) Mice lacking PLAP-1/asporin show alteration of periodontal ligament structures and acceleration of bone loss in periodontitis. Int J Mol Sci 24:15989
Kovacs CS, Chaussain C, Osdoby P, Brandi ML, Clarke B, Thakker RV (2021) The role of biomineralization in disorders of skeletal development and tooth formation. Nat Rev Endocrinol 17:336–349
Larmas M, Hietala EL, Simila S, Pajari U (1991) Oral manifestations of familial hypophosphatemic rickets after phosphate supplement therapy: a review of the literature and report of case. ASDC J Dent Child 58:328–334
Lavicky J, Kolouskova M, Prochazka D, Rakultsev V, Gonzalez-Lopez M, Steklikova K, Bartos M, Vijaykumar A, Kaiser J, Porizka P, Hovorakova M, Mina M, Krivanek J (2022) The development of dentin microstructure is controlled by the type of adjacent epithelium. J Bone Miner Res 37:323–339
Lim D, Wu KC, Lee A, Saunders TL, Ritchie HH (2021) DSPP dosage affects tooth development and dentin mineralization. PLoS ONE 16:e0250429
Lin SX, Zhang Q, Zhang H, Yan K, Ward L, Lu YB, Feng JQ (2014) Nucleus-targeted Dmp1 transgene fails to rescue dental defects in Dmp1 null mice. Int J Oral Sci 6:133–141
Martin-Gonzalez J, Perez-Perez A, Cabanillas-Balsera D, Vilarino-Garcia T, Sanchez-Margalet V, Segura-Egea JJ (2019) Leptin stimulates DMP-1 and DSPP expression in human dental pulp via MAPK 1/3 and PI3K signaling pathways. Arch Oral Biol 98:126–131
Neves VCM, Sharpe PT (2018) Regulation of reactionary dentine formation. J Dent Res 97:416–422
Nieminen P (2009) Genetic basis of tooth agenesis. J Exp Zool B Mol Dev Evol 312B:320–342
Noschang RAT, Seebold D, Walter R, Rivera-Concepcion A, Alraheam IA, Cardoso M, Miguez PA (2021) Stability and remineralization of proteoglycan-infused dentin substrate. Dent Mater 37:1724–1733
Qi G, Yu K, Feng Y, Zhang Y, Shao Q, Yu M, Wang Y, Ren L, Zhu D, Yang G, Jiang Z (2021) 1alpha,25-dihydroxyvitamin D3 promotes early osteogenic differentiation of PDLSCs and a 12-year follow-up case of early-onset vitamin D deficiency periodontitis. J Steroid Biochem Mol Biol 208:105805
Randilini A, Fujikawa K, Shibata S (2020) Expression, localization and synthesis of small leucine-rich proteoglycans in developing mouse molar tooth germ. Eur J Histochem 64:3092
Ricucci D, Loghin S, Lin LM, Spangberg LS, Tay FR (2014) Is hard tissue formation in the dental pulp after the death of the primary odontoblasts a regenerative or a reparative process? J Dent 42:1156–1170
Ricucci D, Siqueira JF Jr, Li Y, Tay FR (2019) Vital pulp therapy: histopathology and histobacteriology-based guidelines to treat teeth with deep caries and pulp exposure. J Dent 86:41–52
Saito K, Nakatomi M, Ida-Yonemochi H, Ohshima H (2016) Osteopontin is essential for type I collagen secretion in reparative dentin. J Dent Res 95:1034–1041
Shah D, Lynd T, Ho D, Chen J, Vines J, Jung HD, Kim JH, Zhang P, Wu H, Jun HW, Cheon K (2020) Pulp-dentin tissue healing response: a discussion of current biomedical approaches. J Clin Med 9:434
Wang Y, Zhu J, DeLuca HF (2012) Where is the vitamin D receptor? Arch Biochem Biophys 523:123–133
Yamakoshi Y (2009) Dentinogenesis and dentin sialophosphoprotein (DSPP). J Oral Biosci 51:134
Ye X, Zhang J, Yang P (2016) Hyperlipidemia induced by high-fat diet enhances dentin formation and delays dentin mineralization in mouse incisor. J Mol Histol 47:467–474
Yu J, Yi L, Guo R, Guo J, Yang H, Huang C (2021) The stability of dentin surface biobarrier consisting of mesoporous delivery system on dentinal tubule occlusion and Streptococcus mutans biofilm inhibition. Int J Nanomedicine 16:3041–3057
Zaugg LK, Banu A, Walther AR, Chandrasekaran D, Babb RC, Salzlechner C, Hedegaard MAB, Gentleman E, Sharpe PT (2020) Translation approach for dentine regeneration using GSK-3 antagonists. J Dent Res 99:544–551
Zhang X, Rahemtulla FG, MacDougall MJ, Thomas HF (2007) Vitamin D receptor deficiency affects dentin maturation in mice. Arch Oral Biol 52:1172–1179
Zhang X, Beck P, Rahemtulla F, Thomas HF (2009a) Regulation of enamel and dentin mineralization by vitamin D receptor. Front Oral Biol 13:102–109
Zhang X, Rahemtulla F, Zhang P, Beck P, Thomas HF (2009b) Different enamel and dentin mineralization observed in VDR deficient mouse model. Arch Oral Biol 54:299–305
Zhang X, Rahemtulla F, Zhang P, Thomas HF (2011) VDR deficiency affects alveolar bone and cementum apposition in mice. Arch Oral Biol 56:672–677
Zhang H, Gong X, Xu X, Wang X, Sun Y (2023) Tooth number abnormality: from bench to bedside. Int J Oral Sci 15:5
Zhao Y, Yuan X, Liu B, Tulu US, Helms JA (2018) Wnt-responsive odontoblasts secrete new dentin after superficial tooth injury. J Dent Res 97:1047–1054
Zhao Y, Yuan X, Bellido T, Helms JA (2019) A correlation between Wnt/beta-catenin signaling and the rate of dentin secretion. J Endod 45(1357–1364):e1351
Acknowledgements
We thank Shanghai Model Organisms Center, Inc., generated Vdr-knockout mice. Thanks for editing this manuscript.
Funding
This work was supported by the Natural Science Fund of Education Department of Anhui Province [KJ2021A0817]; the University Synergy Innovation Program of Anhui Province, China [GXXT-2021-056]; and the Scientific Research Foundation of Education (Graduate Academic Innovation Project) Department of Anhui Province of China [2022xscx126].
Author information
Authors and Affiliations
Contributions
YDL, YLW, and MQS designed the research and wrote the manuscript. YS and SSL analyzed the data and reviewed the manuscript. XDH, GJZ, and QLW contributed to data collation and analysis. All authors reviewed the manuscript.
Corresponding authors
Ethics declarations
Ethical approval
All experiments involving animals were performed in accordance with the guidelines for the Care and Use of Laboratory Animals and monitored by the Institutional Animal Care and Use Committee of Bengbu Medical College (BBMC-2022-204).
Informed consent
Not applicable.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Liu, Y., Wu, Y., Hu, X. et al. The role of vitamin D receptor in predentin mineralization and dental repair after injury. Cell Tissue Res (2024). https://doi.org/10.1007/s00441-024-03886-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00441-024-03886-7