pmjТихоокеанский медицинский журналPacific Medical Journal1609-1175TGMU10.34215/1609-1175-2024-1-11-16pmj-2682Research ArticleОБЗОРЫREVIEWSМорфогенетические и ростовые факторы в механизмах повреждения дентино-пульпарного комплекса и периодонтаMorphogenetic and growth factors in damaging to the dentin-pulp complex and periodontiumЕдрановС. С.EdranovS. S.

Владивосток 

Vladivostok

КалиниченкоС. Г.KalinichenkoS. G.

Владивосток

Vladivostok

https://orcid.org/0000-0003-0844-7950МатвееваН. Ю.MatveevaN. Yu.

Матвеева Наталья Юрьевна – д-р мед. наук, заведующий кафедрой гистологии, эмбриологии и цитологии 

690002, г. Владивосток, пр. Острякова, 2 

Natalya Yu. Matveeva, Dr. Sci. (Med.), Head of the Department of Histology, Embryology and Cytology 

2 Ostryakova Ave, Vladivostok, 690002 

nymatveeva@mail.ruКовалёваИ. В.KovalevaI. V.

Владивосток

Vladivostok

Тихоокеанский государственный медицинский университетРоссияPacific State Medical UniversityRussian Federation202418052024011116Copyright © Едранов С.С., Калиниченко С.Г., Матвеева Н.Ю., Ковалёва И.В., 20242024Едранов С.С., Калиниченко С.Г., Матвеева Н.Ю., Ковалёва И.В.Edranov S.S., Kalinichenko S.G., Matveeva N.Y., Kovaleva I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.tmj-vgmu.ru/jour/article/view/2682

Морфогенетические и ростовые молекулы – ключевые участники репаративного дентиногенеза – определяют жизнеспособность дентино-пульпарного комплекса (ДПК), периодонта и зубодесневого соединения. Они секретируются в микрососудах, нервных волокнах и соединительнотканных клетках пульпы зуба, оказывая гомеостатическое влияние на ближайшее окружение. В обзоре суммированы данные по локализации факторов роста и сигнальным механизмам, которые контролируют гистогенез и репаративные процессы в ДПК. Указывается особое значение этих факторов в регуляции провоспалительных и иммунокомпетентных клеток при кариесе, пародонтите и остеоиндуктивных процессах в альвеолярном отростке. Исследование ростовых молекул имеет решающее значение в разработке новейших клинических стратегий, направленных на поддержание жизнеспособности ДПК и интеграции искусственных материалов при восстановлении тканей зуба.

Morphogenetic and growth molecules, a key participant in reparative dentinogenesis, determine viability of the dentin-pulp complex (DPC), periodontium and dentogingival junction. They are secreted in microvessels, nerve fibers and connective tissue cells of the dental pulp, exerting homeostatic influence on the immediate surrounding. The present paper reviews the data on the localization of growth factors and signaling mechanisms that control histogenesis and reparative processes in the DPC. The paper points out the significance of these factors in the regulation of proinflammatory and immunocompetent cells in caries, periodontitis and osteoinductive processes in the alveolar outgrowth. The study of growth molecules appears crucial in the development of the latest clinical strategies to maintain the viability of the DPC and to integrate artificial materials in dental tissue restoration.

дентиногенезпериодонтдентино-пульпарный комплексростовые молекулыdentinogenesisperiodontiumdentin-pulp complexgrowth moleculesReferencesВавилова Т.П., Островская И.Г. Биохимия и физиология пульпы зуба. М.: Медиа-Сфера, 2008. 136 с.Vavilova TP, Ostrovskaya IG. Biochemistry and physiology of dental pulp. M.: Media-Sfera, 2008. 136 p. (In Russ.)Сирак С.В., Сирак А.Г., Копылова И.А., Бирагова А.К. Изучение морфологических изменений в пульпе зубов экспериментальных животных при лечении глубокого кариеса и острого очагового пульпита. Медицинский вестник Северного Кавказа. 2011;23(3):29–33.Sirak SV, Sirak AG, Kopylova IA, Biragova AK. Study of morphological changes in the dental pulp of experimental animals during the treatment of deep caries and acute focal pulpitis. Medical News of the North Caucasus. 2011;23(3):29–33 (In Russ.)Farges JC, Alliot-Licht B, Renard E, Ducret M, Gaudin A, Smith AJ, Cooper PR. Dental pulp defence and repair mechanisms in dental caries. Mediators Inflamm. 2015;2015:230251. doi: 10.1155/2015/230251Farges JC, Alliot-Licht B, Renard E, Ducret M, Gaudin A, Smith AJ, Cooper PR. Dental pulp defence and repair mechanisms in dental caries. Mediators Inflamm. 2015;2015:230251. doi: 10.1155/2015/230251Goldberg M. The dental pulp. Biology, patology, and regenerative therapies. London: Springer; Hiedelberg; New York; Dordrecht, 2014. 277 p.Goldberg M. The dental pulp. Biology, patology, and regenerative therapies. London: Springer; Hiedelberg; New York; Dordrecht, 2014. 277 p.Freitas P, Novaretti CP, Rodini CO, Batista AC, Lara VS. Mast cells and lymphocyte subsets in pulps from healthy and carious human teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(5):e95–102. doi: 10.1016/j.tripleo.2006.11.031Freitas P, Novaretti CP, Rodini CO, Batista AC, Lara VS. Mast cells and lymphocyte subsets in pulps from healthy and carious human teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(5):e95–102. doi: 10.1016/j.tripleo.2006.11.031Li J, Parada C, Chai Y. Cellular and molecular mechanisms of tooth root development. Development. 2017;144(3):374–84. doi: 10.1242/dev.137216Li J, Parada C, Chai Y. Cellular and molecular mechanisms of tooth root development. Development. 2017;144(3):374–84. doi: 10.1242/dev.137216Emilia E, Neelakantan P. Biomarkers in the dentin-pulp complex: role in health and disease. J Clin Pediatr Dent. 2015;39(2):94–9. doi: 10.17796/jcpd.39.2.r32617516412p710Emilia E, Neelakantan P. Biomarkers in the dentin-pulp complex: role in health and disease. J Clin Pediatr Dent. 2015;39(2):94–9. doi: 10.17796/jcpd.39.2.r32617516412p710Zhao J, Birjandi AA, Ahmed M, Redhead Y, Olea JV, Sharpe P. Telocytes regulate macrophages in periodontal disease. Elife. 2022;11:e72128. doi: 10.7554/eLife.72128Zhao J, Birjandi AA, Ahmed M, Redhead Y, Olea JV, Sharpe P. Telocytes regulate macrophages in periodontal disease. Elife. 2022;11:e72128. doi: 10.7554/eLife.72128Piglionico SS, Pons C, Romieu O, Cuisinier F, Levallois B, Panayotov IV. In vitro, ex vivo, and in vivo models for dental pulp regeneration. J Mater Sci Mater Med. 2023;34(4):15. doi: 10.1007/s10856-023-06718-2Piglionico SS, Pons C, Romieu O, Cuisinier F, Levallois B, Panayotov IV. In vitro, ex vivo, and in vivo models for dental pulp regeneration. J Mater Sci Mater Med. 2023;34(4):15. doi: 10.1007/s10856-023-06718-2Baysal E, Zırh EB, Buber E, Jakobsen TK, Zeybek ND. The effect of melatonin on Hippo signaling pathway in dental pulp stem cells. Neurochem Int. 2021;148:105079. doi: 10.1016/j.neuint.2021.105079Baysal E, Zırh EB, Buber E, Jakobsen TK, Zeybek ND. The effect of melatonin on Hippo signaling pathway in dental pulp stem cells. Neurochem Int. 2021;148:105079. doi: 10.1016/j.neuint.2021.105079Morsczeck C, Reichert TE. Dental stem cells in tooth regeneration and repair in the future. Expert Opin Biol Ther. 2018;18(2):187–96. doi: 10.1080/14712598.2018.1402004Morsczeck C, Reichert TE. Dental stem cells in tooth regeneration and repair in the future. Expert Opin Biol Ther. 2018;18(2):187–96. doi: 10.1080/14712598.2018.1402004Hsu EL, Stock SR. Growth factors, carrier materials, and bone repair. Handb Exp Pharmacol. 2020;262:121–56. doi: 10.1007/164_2020_371Hsu EL, Stock SR. Growth factors, carrier materials, and bone repair. Handb Exp Pharmacol. 2020;262:121–56. doi: 10.1007/164_2020_371Костив Р.Е., Калиниченко С.Г., Матвеева Н.Ю. Трофические факторы роста костной ткани, их морфогенетическая характеристика и клиническое значение. Тихоокеанский медицинский журнал. 2017;(1):10–6. doi: 10.17238/PmJ1609-1175.2017.1.10-16Kostiv RE, Kalinichenko SG, Matveeva NYu. Trophic factors of bone growth, their morphogenetic characterization and clinical significance. Pacific Medical Journal. 2017;(1):10–6 (In Russ.). doi: 10.17238/PmJ1609-1175.2017.1.10-16Li W, Wei W, Ding S. TGF-β signaling in stem cell regulation. Methods Mol Biol. 2016;1344:137-45. doi: 10.1007/978-1-4939-2966-5_8Li W, Wei W, Ding S. TGF-β signaling in stem cell regulation. Methods Mol Biol. 2016;1344:137-45. doi: 10.1007/978-1-4939-2966-5_8Kowalczewski CJ, Saul JM. Biomaterials for the delivery of growth factors and other therapeutic agents in tissue engineering approaches to bone regeneration. Front Pharmacol. 2018;9:513. doi: 10.3389/fphar.2018.00513.eCollection2018Kowalczewski CJ, Saul JM. Biomaterials for the delivery of growth factors and other therapeutic agents in tissue engineering approaches to bone regeneration. Front Pharmacol. 2018;9:513. doi: 10.3389/fphar.2018.00513.eCollection2018Raja S, Byakod G, Pudakalkatti P. Growth factors in periodontal regeneration. Int J Dent Hyg. 2009;7(2):82–9. doi: 10.1111/j.1601-5037.2009.00380.xRaja S, Byakod G, Pudakalkatti P. Growth factors in periodontal regeneration. Int J Dent Hyg. 2009;7(2):82–9. doi: 10.1111/j.1601-5037.2009.00380.xChang HH, Chang MC, Wu IH, Huang GF, Huang WL, Wang YL, Lee SY, Yeh CY, Guo MK, Chan CP, Hsien HC, Jeng JH. Role of ALK5/Smad2/3 and MEK1/ERK signaling in transforming growth factor beta 1-modulated growth, collagen turnover, and differentiation of stem cells from apical papilla of human tooth. J Endod. 2015;41(8):1272–80. doi: 10.1016/j.joen.2015.03.022Chang HH, Chang MC, Wu IH, Huang GF, Huang WL, Wang YL, Lee SY, Yeh CY, Guo MK, Chan CP, Hsien HC, Jeng JH. Role of ALK5/Smad2/3 and MEK1/ERK signaling in transforming growth factor beta 1-modulated growth, collagen turnover, and differentiation of stem cells from apical papilla of human tooth. J Endod. 2015;41(8):1272–80. doi: 10.1016/j.joen.2015.03.022Botero TM, Son JS, Vodopyanov D, Hasegawa M, Shelburne CE, Nör JE. MAPK signaling is required for LPS-induced VEGF in pulp stem cells. J Dent Res. 2010;89(3):264–9. doi: 10.1177/0022034509357556Botero TM, Son JS, Vodopyanov D, Hasegawa M, Shelburne CE, Nör JE. MAPK signaling is required for LPS-induced VEGF in pulp stem cells. J Dent Res. 2010;89(3):264–9. doi: 10.1177/0022034509357556Едранов С.С., Матвеева Н.Ю., Калиниченко С.Г. Накостная фиксация свободного десневого трансплантата вызывает остеоиндуктивный эффект в альвеолярной кости человека. Клеточные технологии в биологии и медицине. 2021;(3):201– 7. doi: 10.47056/1814-3490-2021-3-201-207Edranov SS, Matveeva NYu, Kalinichenko SG. On-bone fixation of free gingival graft causes osteoinductive effect in human alveolar bone. Cell Technologies in Biology and Medicine.2021;(3):201–7 (In Russ.) doi: 10.47056/1814-3490-2021-3-201-207Al-Khafaji H, Noer PR, Alkharobi H, Alhodhodi A, Meade J, El-Gendy R, Oxvig C, Beattie J. A characteristic signature of insulin-like growth factor (IGF) axis expression during osteogenic differentiation of human dental pulp cells (hDPCs): Potential co-ordinated regulation of IGF action. Growth Horm IGF Res. 2018;42-43:14–21. doi: 10.1016/j.ghir.2018.07.003Al-Khafaji H, Noer PR, Alkharobi H, Alhodhodi A, Meade J, El-Gendy R, Oxvig C, Beattie J. A characteristic signature of insulin-like growth factor (IGF) axis expression during osteogenic differentiation of human dental pulp cells (hDPCs): Potential co-ordinated regulation of IGF action. Growth Horm IGF Res. 2018;42-43:14–21. doi: 10.1016/j.ghir.2018.07.003Hwang YC, Hwang IN, Oh WM, Park JC, Lee DS, Son HH. Influence of TGF-beta1 on the expression of BSP, DSP, TGFbeta1 receptor I and Smad proteins during reparative dentinogenesis. J Mol Histol. 2008;39(2):153–60. doi: 10.1007/s10735-007-9148-8Hwang YC, Hwang IN, Oh WM, Park JC, Lee DS, Son HH. Influence of TGF-beta1 on the expression of BSP, DSP, TGFbeta1 receptor I and Smad proteins during reparative dentinogenesis. J Mol Histol. 2008;39(2):153–60. doi: 10.1007/s10735-007-9148-8Wang Y, Cox MK, Coricor G, MacDougall M, Serra R. Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation. Dev Biol. 2013;382:27–37. doi: 10.1016/j.ydbio.2013.08.003Wang Y, Cox MK, Coricor G, MacDougall M, Serra R. Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation. Dev Biol. 2013;382:27–37. doi: 10.1016/j.ydbio.2013.08.003Gao Y, Yang G, Weng T, Du J, Wang X, Zhou J, Wang S, Yang X. Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice. Mol Cell Biol. 2009;29:5941–51. doi:10.1128/MCB.00706-09Gao Y, Yang G, Weng T, Du J, Wang X, Zhou J, Wang S, Yang X. Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice. Mol Cell Biol. 2009;29:5941–51. doi:10.1128/MCB.00706-09Lapthanasupkul P, Feng J, Mantesso A, Takada-Horisawa Y, Vidal M, Koseki H, Wang L, An Z, Miletich I, Sharpe PT. Ring1a/b polycomb proteins regulate the mesenchymal stem cell niche in continuously growing incisors. Dev. Biol. 2012;367:140–53. doi: 10.1016/j.ydbio.2012.04.029Lapthanasupkul P, Feng J, Mantesso A, Takada-Horisawa Y, Vidal M, Koseki H, Wang L, An Z, Miletich I, Sharpe PT. Ring1a/b polycomb proteins regulate the mesenchymal stem cell niche in continuously growing incisors. Dev. Biol. 2012;367:140–53. doi: 10.1016/j.ydbio.2012.04.029Sanz JL, Rodríguez-Lozano FJ, Llena C, Sauro S, Forner L. Bioactivity of bioceramic materials used in the dentin-pulp complex therapy: a systematic review. Materials (Basel). 2019;12(7):1015. doi: 10.3390/ma12071015Sanz JL, Rodríguez-Lozano FJ, Llena C, Sauro S, Forner L. Bioactivity of bioceramic materials used in the dentin-pulp complex therapy: a systematic review. Materials (Basel). 2019;12(7):1015. doi: 10.3390/ma12071015Иванов С.Ю., Карасенков Я.Н., Латута Н.В., Джатдаев В.В., Егоров Е.А., Тарасова Е.К., Козлова Э.В., Козлов П.А. Применение наночастиц металлов и их оксидов в стоматологических композитных материалах и конструкциях. Обзор (часть 1). Клиническая стоматология. 2022;25(4):159–65. doi: 10.37988/1811-153X_2022_4_159Ivanov SYu, Karasenkov YaN, Latuta NV, Dzhatdaev VV, Egorov EA, Tarasova EK, Kozlova EV, Kozlov PA. Application of metal nanoparticles and their oxides in dental composite materials and structures: A review (part I). Clinical Dentistry. 2022;25(4):159–65 (In Russ.) doi: 10.37988/1811-153X_2022_4_159Луцкая И.К., Чухрай И.Г., Новак Н.В. Эндодонтия: практическое руководство. М.: Медицинская литература, 2009. 191 с.Lutskaya IK, Chukhrai IG, Novak NV. Endodontics: a practical guide. Moscow, Medicinskaja Literatura, 2009. 191 p. (In Russ.)Lambrichts I, Driesen RB, Dillen Y, Gervois P, Ratajczak J, Vangansewinkel T, Wolfs E, Bronckaers A, Hilkens P. Dental pulp stem cells: their potential in reinnervation and angiogenesis by using scaffolds. J Endod. 2017;43(9S):S12–S16. doi: 10.1016/j.joen.2017.06.001Lambrichts I, Driesen RB, Dillen Y, Gervois P, Ratajczak J, Vangansewinkel T, Wolfs E, Bronckaers A, Hilkens P. Dental pulp stem cells: their potential in reinnervation and angiogenesis by using scaffolds. J Endod. 2017;43(9S):S12–S16. doi: 10.1016/j.joen.2017.06.001Костив Р.Е., Матвеева Н.Ю., Калиниченко С.Г. Биоактивные покрытия на металлических сплавах и стимуляция восстановления кости после перелома. Тихоокеанский медицинский журнал. 2021;(2):31–6. doi: 10.34215/1609-1175-2021-2-31-36Kostiv RE, Matveeva NYu, Kalinichenko SG. Bioactive coatings on metallic alloys and stimulation of bone repair after fracture. Pacific Medical Journal. 2021;(2):31–6 (In Russ.) doi: 10.34215/1609-1175-2021-2-31-36Калиниченко С.Г., Матвеева Н.Ю., Костив Р.Е., Пузь А.В. Сосудистый эндотелиальный фактор роста и трансформирующий фактор роста-β2 в костной ткани крыс при установке после перелома титановых имплантатов с биоактивными биорезорбируемыми покрытиями. Бюлл. эксп. биол. и мед. 2016;162(11):626–31. doi: 10.1007/s10517-017-3684-3Kalinichenko SG, Matveeva NYu, Kostiv RE, Puz’ AV. Role of Vascular Endothelial Growth Factor and Transforming Growth Factor-β2 in Rat Bone Tissue after Bone Fracture and Placement of Titanium Implants with Bioactive Bioresorbable Coatings. Bull Exp Biol Med. 2016;162(11):626–31 (In Russ.) doi: 10.1007/s10517-017-3684-3Liu M, Goldman G, MacDougall M, Chen S. BMP signaling pathway in dentin development and diseases. Cells. 2022;11(14):2216. doi: 10.3390/cells11142216Liu M, Goldman G, MacDougall M, Chen S. BMP signaling pathway in dentin development and diseases. Cells. 2022;11(14):2216. doi: 10.3390/cells11142216Liang C, Liang Q, Xu X, Liu X, Gao X, Li M, Yang J, Xing X, Huang H, Tang Q, Liao L, Tian W. Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: therapeutic potential for endogenous pulp regeneration. Int J Oral Sci. 2022;14(1):38. doi: 10.1038/s41368-022-00188-yLiang C, Liang Q, Xu X, Liu X, Gao X, Li M, Yang J, Xing X, Huang H, Tang Q, Liao L, Tian W. Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: therapeutic potential for endogenous pulp regeneration. Int J Oral Sci. 2022;14(1):38. doi: 10.1038/s41368-022-00188-yZhang Y, Liu J, Zou T, Qi Y, Yi B, Dissanayaka WL, Zhang C. DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling. Stem Cell Res Ther. 2021;12(1):281. doi: 10.1186/s13287-021-02349-yZhang Y, Liu J, Zou T, Qi Y, Yi B, Dissanayaka WL, Zhang C. DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling. Stem Cell Res Ther. 2021;12(1):281. doi: 10.1186/s13287-021-02349-yRutherford RB. BMP-7 gene transfer to inflamed ferret dental pulps. Eur J Oral Sci. 2001;109(6):422–4. doi: 10.1034/j.1600-0722.2001.00150.xRutherford RB. BMP-7 gene transfer to inflamed ferret dental pulps. Eur J Oral Sci. 2001;109(6):422–4. doi: 10.1034/j.1600-0722.2001.00150.xGaller KM, D’Souza RN. Tissue engineering approaches for regenerative dentistry. Regen Med. 2011;6(1):111–24. doi: 10.2217/rme.10.86Galler KM, D’Souza RN. Tissue engineering approaches for regenerative dentistry. Regen Med. 2011;6(1):111–24. doi: 10.2217/rme.10.86Diana R, Ardhani R, Kristanti Y, Santosa P. Dental pulp stem cells response on the nanotopography of scaffold to regenerate dentin-pulp complex tissue. Regen Ther. 2020;15:243–50. doi: 10.1016/j.reth.2020.09.007Diana R, Ardhani R, Kristanti Y, Santosa P. Dental pulp stem cells response on the nanotopography of scaffold to regenerate dentin-pulp complex tissue. Regen Ther. 2020;15:243–50. doi: 10.1016/j.reth.2020.09.007Steindorff MM, Lehl H, Winkel A, Stiesch M. Innovative approaches to regenerate teeth by tissue engineering. Arch Oral Biol. 2014;59(2):158–66. doi: 10.1016/j.archoralbio.2013.11.005Steindorff MM, Lehl H, Winkel A, Stiesch M. Innovative approaches to regenerate teeth by tissue engineering. Arch Oral Biol. 2014;59(2):158–66. doi: 10.1016/j.archoralbio.2013.11.005Панкратьева Э.П., Афанасенко В.А., Кунавина К.А., Гагарина Т.Ю., Шиловская К.А. Инвазивная цервикальная резорбция как осложнение внутрикоронкового отбеливания. Медицинский алфавит. 2022;(7):69–73. doi: 10.33667/2078-5631-2022-7-69-73Pankratieva EP, Afanasenko VA, Kunavina KA, Gagarina TYu, Shilovskaya KA. Invasive cervical resorption as a complication of intracoronal bleaching. Medical Alphabet. 2022;(7):69–73 (In Russ.) doi: 10.33667/2078-5631-2022-7-69-73Едранов С.С., Матвеева Н.Ю., Калиниченко С.Г. Остеогенный и регенераторный потенциал свободного десневого трансплантата. Бюлл. эксп. биол. и мед. 2021;171(3):391–6. doi: 10.47056/0365-9615-2021-171-3-391-396Edranov SS, Matveeva NYu, Kalinichenko SG. Osteogenic and regenerative potential of the free gingival graft. Bull Exp Biol Med. 2021;171(3):391–6 (In Russ.) doi: 10.47056/0365-9615-2021-171-3-391-396

The authors declare that there are no conflicts of interest present.