Abstract
Human periodontal ligament cells (hPDLCs) are known as ideal seed cells for the regeneration of periodontal tissues. Several factors (i.e., vitamin D3, luteolin, and 6-bromoindirubin-3′-oxime) have been shown to promote osteogenic differentiation of hPDLCs. In this study, we aim to investigate the effect of vitamin A on cell proliferation, migration, and osteogenic differentiation of hPDLCs. hPDLCs were cultured in osteogenic induction medium supplemented with different concentrations of vitamin A. Cell proliferation and migration assays were conducted after 24, 48, and 72 h of incubation, whereas osteogenic differentiation and osteogenesis-related gene expression were assessed after 21 d only. Our results demonstrated that 1-µM vitamin A stimulation exerted the most potent promotion effect on cell proliferation, migration, and osteogenic differentiation of hPDLCs. It also induced significant upregulation of osteogenic differentiation–related genes and mitochondrial complexes II and IV in hPDLCs. Vitamin A may serve as a promising potential candidate for periodontal tissue regeneration.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A (2019) The Role of Vitamins and Minerals in Hair Loss: a Review. Dermatol Ther (heidelb) 9:51–70. https://doi.org/10.1007/s13555-018-0278-6
Blufstein A, Behm C, Kubin B, Gahn J, Moritz A, Rausch-Fan X, Andrukhov O (2021) Transcriptional activity of vitamin D receptor in human periodontal ligament cells is diminished under inflammatory conditions. J Periodontol 92:137–148. https://doi.org/10.1002/JPER.19-0541
Blufstein A, Behm C, Kubin B, Gahn J, Rausch-Fan X, Moritz A, Andrukhov O (2021) Effect of vitamin D3 on the osteogenic differentiation of human periodontal ligament stromal cells under inflammatory conditions. J Periodontal Res 56:579–588. https://doi.org/10.1111/jre.12858
Botelho J, Machado V, Proenca L, Delgado AS, Mendes JJ (2020) Vitamin D deficiency and oral health: a comprehensive review. Nutrients 12:1471. https://doi.org/10.3390/nu12051471
Bousnaki M, Beketova A, Kontonasaki E (2022) A review of in vivo and clinical studies applying scaffolds and cell sheet technology for periodontal ligament regeneration. Biomolecules 12:435. https://doi.org/10.3390/biom12030435
Brown CC, Noelle RJ (2015) Seeing through the dark: new insights into the immune regulatory functions of vitamin A. Eur J Immunol 45:1287–1295. https://doi.org/10.1002/eji.201344398
Cagetti MG, Wolf TG, Tennert C, Camoni N, Lingstrom P, Campus G (2020) The role of vitamins in oral health. A systematic review and meta-analysis. Int J Environ Res Public Health 17:938. https://doi.org/10.3390/ijerph17030938
Chadipiralla K, Yochim JM, Bahuleyan B, Huang CY, Garcia-Godoy F, Murray PE, Stelnicki EJ (2010) Osteogenic differentiation of stem cells derived from human periodontal ligaments and pulp of human exfoliated deciduous teeth. Cell Tissue Res 340:323–333. https://doi.org/10.1007/s00441-010-0953-0
Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P (2013) Vitamin C in disease prevention and cure: an overview Indian. J Clin Biochem 28:314–328. https://doi.org/10.1007/s12291-013-0375-3
Clagett-Dame M, Knutson D (2011) Vitamin A in reproduction and development. Nutrients 3:385–428. https://doi.org/10.3390/nu3040385
Fishman SM, Christian P, West KP (2000) The role of vitamins in the prevention and control of anaemia. Public Health Nutr 3:125–150. https://doi.org/10.1017/s1368980000000173
Gao Z, Liu K, Meng H (2018) Preliminary investigation of the vitamin D pathway in periodontal connective tissue cells. J Periodontol 89:294–302. https://doi.org/10.1002/JPER.17-0530
Gasner NS, Schure RS (2022) Periodontal disease. In: StatPearls. StatPearls Publishing, Treasure Island, FL
Guo L, Zhang Y, Liu H, Cheng Q, Yang S, Yang D (2022) All-trans retinoic acid inhibits the osteogenesis of periodontal ligament stem cells by promoting IL-1beta production via NF-kappaB signaling. Int Immunopharmacol 108:108757. https://doi.org/10.1016/j.intimp.2022.108757
Gutierrez Gossweiler A, Martinez-Mier EA (2020) Chapter 6: vitamins and oral health. Monogr Oral Sci 28:59–67. https://doi.org/10.1159/000455372
Ji Y et al (2019) Effect of 1alpha, 25-dihydroxyvitamin D3 on the osteogenic differentiation of human periodontal ligament stem cells and the underlying regulatory mechanism. Int J Mol Med 43:167–176. https://doi.org/10.3892/ijmm.2018.3947
Khanna-Jain R, Vuorinen A, Sandor GK, Suuronen R, Miettinen S (2010) Vitamin D(3) metabolites induce osteogenic differentiation in human dental pulp and human dental follicle cells. J Steroid Biochem Mol Biol 122:133–141. https://doi.org/10.1016/j.jsbmb.2010.08.001
Kinane DF, Stathopoulou PG, Papapanou PN (2017) Periodontal diseases. Nat Rev Dis Primers 3:17038. https://doi.org/10.1038/nrdp.2017.38
Li J et al (2021) Dynamic proteomic profiling of human periodontal ligament stem cells during osteogenic differentiation. Stem Cell Res Ther 12:98. https://doi.org/10.1186/s13287-020-02123-6
Liu J, Lu Y, Liu J, Jin C, Meng Y, Pei D (2019) Influence of epigallocatechin-3-gallate in promoting proliferation and osteogenic differentiation of human periodontal ligament cells. BMC Oral Health 19:73. https://doi.org/10.1186/s12903-019-0768-7
Liu Y et al (2018) All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies. Drug Des Devel Ther 12:3419–3430. https://doi.org/10.2147/DDDT.S178190
Lowe H, Toyang N, Steele B, Bryant J, Ngwa W, Nedamat K (2021) The current and potential application of medicinal cannabis products in dentistry. Dent J (Basel) 9:106. https://doi.org/10.3390/dj9090106
Michaud DS, Fu Z, Shi J, Chung M (2017) Periodontal disease, tooth loss, and cancer risk. Epidemiol Rev 39:49–58. https://doi.org/10.1093/epirev/mxx006
Quan H, Dai X, Liu M, Wu C, Wang D (2019) Luteolin supports osteogenic differentiation of human periodontal ligament cells. BMC Oral Health 19:229. https://doi.org/10.1186/s12903-019-0926-y
Rubinoff AB, Latner PA, Pasut LA (1989) Vitamin C and oral health. J Can Dent Assoc 55:705–707
San Miguel SM, Goseki-Sone M, Sugiyama E, Watanabe H, Yanagishita M, Ishikawa I (1998) The effects of retinoic acid on alkaline phosphatase activity and tissue-non-specific alkaline phosphatase gene expression in human periodontal ligament cells and gingival fibroblasts. J Periodontal Res 33:428–433. https://doi.org/10.1111/j.1600-0765.1998.tb02339.x
Shen S et al (2021) 6-Bromoindirubin-3′-oxime promotes osteogenic differentiation of periodontal ligament stem cells and facilitates bone regeneration in a mouse periodontitis model. ACS Biomater Sci Eng 7:232–241. https://doi.org/10.1021/acsbiomaterials.0c01078
Shibuya N, Nemoto E, Kanaya S, Kunii R, Shimauchi H (2005) Retinoic acid is a potential negative regulator for differentiation of human periodontal ligament cells. J Periodontal Res 40:432–440. https://doi.org/10.1111/j.1600-0765.2005.00811.x
Smith CO, Eliseev RA (2021) Energy metabolism during osteogenic differentiation: the role of Akt. Stem Cells Dev 30:149–162. https://doi.org/10.1089/scd.2020.0141
Stocklin E, Eggersdorfer M (2013) Vitamin D, an essential nutrient with versatile functions in nearly all organs. Int J Vitam Nutr Res 83:92–100. https://doi.org/10.1024/0300-9831/a000151
Tardy AL, Pouteau E, Marquez D, Yilmaz C, Scholey A (2020) Vitamins and minerals for energy, fatigue and cognition: a narrative review of the biochemical and clinical evidence. Nutrients 12:228. https://doi.org/10.3390/nu12010228
Wang Y, Wang SZ, Yang PS, Li S (2004) The biological effect of retinoic acid on cultured human periodontal ligament cells. Shanghai Kou Qiang Yi Xue 13:297–300
Xiang L, Ma L, He Y, Wei N, Gong P (2014) Osteogenic differentiation of human periodontal ligament cells after transfection with recombinant lentiviral vector containing follicular dendritic cell secreted protein. J Periodontal Res 49:554–562. https://doi.org/10.1111/jre.12135
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ZBL participated in the design of experiments and manuscript preparation. JW and ZBL helped with assays and analyses. JW supervised processes of experiments and manuscript preparation. All authors read and approved the final manuscript.
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Wang, J., Li, Z. Effects of vitamin A in promoting proliferation and osteogenic differentiation of human periodontal ligament cells. In Vitro Cell.Dev.Biol.-Animal 59, 121–130 (2023). https://doi.org/10.1007/s11626-023-00754-6
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DOI: https://doi.org/10.1007/s11626-023-00754-6