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DOI: 10.1055/a-1830-9347
Präklinische Zell- und Tiermodelle zur Untersuchung der Auswirkungen des Parathormons auf den Zahnhalteapparat
Preclinical Cell and Animal Models to Study the Effects of Parathyroid Hormone on the PeriodontiumZusammenfassung
Das Parathormon (PTH) oder das Parathormon verwandte Protein (PTHrP) binden an den Parathormon Rezeptor Typ 1 (PTH1R) und lösen somit unterschiedliche biochemische Antworten aus. Der PTH1R gehört zur Familie der G-Protein gekoppelten Rezeptoren und reguliert die Calciumhomöostase und die Knochenbildung. Im Zahnhalteapparat sind Mutationen im PTH1R mit Zahndurchbruchsstörung assoziiert und bringen einen Verlust des Alveolarknochens mit sich.
Durch präklinische in vitro Studien konnte gezeigt werden, dass PTH einen positiven Einfluss auf die Proliferation und die Differenzierung von Zellen aus dem parodontalen Ligament hat. Die intermittierende Verabreichung von PTH in vivo hat in unterschiedlichen Studien einen positiven Einfluss auf den Alveolarknochenverlust bewirkt, was eine Grundlage für einen Therapieansatz in dentalen Erkrankungen darstellt. Jedoch sind die molekularbiologischen Zusammenhänge bei der intermittierenden Applikation von PTH noch nicht bekannt, weshalb weitere Untersuchungen notwendig sind.
In diesem kurzen Übersichtsartikel werden daher verschiedene Studien über die Verabreichung von PTH und seine Auswirkungen auf den Zahnhalteapparat verglichen.
Abstract
The parathyroid hormone (PTH) and the parathyroid hormone related protein (PTHrP) both can bind to the parathyroid hormone receptor type 1 (PTH1R), thus triggering different biochemical signaling cascades. The PTH1R belongs to the family of g-protein coupled receptors and regulates calcium homeostasis and bone formation. In the periodontium, mutations of PTH1R play a role in primary failure of eruption (PFE) and entail the loss of the alveolar bone.
In vitro studies have shown that PTH has a positive effect on the proliferation and differentiation of cells from the periodontal ligament. The intermittent administration of PTH in vivo in different studies revealed a positive impact on the alveolar bone loss, providing a basis for a therapeutic approach in dental diseases. However, the molecular biological relationships involved in the intermittent application of PTH are not yet known, so further investigations are needed.
This short review article compares different studies on the administration of PTH and its effects on the periodontium.
Key words
parathyroid hormone - parathyroid hormone related protein - parathyroid hormone receptor type 1 - primary failure of eruption - periodontium - periodontitisPublikationsverlauf
Eingereicht: 12. Januar 2022
Angenommen: 20. April 2022
Artikel online veröffentlicht:
30. Mai 2022
© 2022. Thieme. All rights reserved.
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Germany
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Literatur
- 1 Cheloha RW, Gellman SH, Vilardaga J-P. et al. PTH receptor-1 signalling—mechanistic insights and therapeutic prospects. Nature Reviews Endocrinology 2015; 11: 712-724 DOI: 10.1038/nrendo.2015.139.
- 2 Murray TM, Rao LG, Divieti P. et al. Parathyroid Hormone Secretion and Action: Evidence for Discrete Receptors for the Carboxyl-Terminal Region and Related Biological Actions of Carboxyl-Terminal Ligands. Endocrine Reviews 2005; 26: 78-113 DOI: 10.1210/er.2003-0024.
- 3 Barros SP, Silva MA, Somerman MJ. et al. Parathyroid hormone protects against periodontitis-associated bone loss. J Dent Res 2003; 82: 791-795 DOI: 10.1177/154405910308201006.
- 4 Silva BC, Bilezikian JP. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol 2015; 22: 41-50 DOI: 10.1016/j.coph.2015.03.005.
- 5 Vilardaga JP, Romero G, Friedman PA. et al. Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm. Cell Mol Life Sci 2011; 68: 1-13 DOI: 10.1007/s00018-010-0465-9.
- 6 Jüppner H, Abou-Samra AB, Freeman M. et al. A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 1991; 254: 1024-1026 DOI: 10.1126/science.1658941.
- 7 Sutkeviciute I, Clark LJ, White AD. et al. PTH/PTHrP Receptor Signaling, Allostery, and Structures. Trends Endocrinol Metab 2019; 30: 860-874 DOI: 10.1016/j.tem.2019.07.011.
- 8 Wein MN., Kronenberg HM. Regulation of Bone Remodeling by Parathyroid Hormone. Cold Spring Harb Perspect Med 2018; 8 DOI: 10.1101/cshperspect.a031237.
- 9 Wysolmerski JJ, Cormier S, Philbrick WM. et al. Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. J Clin Endocrinol Metab 2001; 86: 1788-1794 DOI: 10.1210/jcem.86.4.7404.
- 10 Philbrick WM, Dreyer BE, Nakchbandi IA. et al. Parathyroid hormone-related protein is required for tooth eruption. Proc Natl Acad Sci U S A 1998; 95: 11846-11851 DOI: 10.1073/pnas.95.20.11846.
- 11 Decker E, Stellzig-Eisenhauer A, Fiebig BS. et al. PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet 2008; 83: 781-786 DOI: 10.1016/j.ajhg.2008.11.006.
- 12 Subramanian H, Döring F, Kollert S. et al. PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling. PLOS ONE 2016; 11: e0167033 DOI: 10.1371/journal.pone.0167033.
- 13 Proffit WR, Vig KW. Primary failure of eruption: a possible cause of posterior open-bite. Am J Orthod 1981; 80: 173-190 DOI: 10.1016/0002-9416(81)90217-7.
- 14 Stellzig-Eisenhauer A, Decker E, Meyer-Marcotty P. et al. Primary failure of eruption (PFE) – clinical and molecular genetics analysis. J Orofac Orthop 2010; 71: 6-16 DOI: 10.1007/s00056-010-0908-9.
- 15 Nagata M, Ono N, Ono W. Mesenchymal Progenitor Regulation of Tooth Eruption: A View from PTHrP. J Dent Res 2020; 99: 133-142 DOI: 10.1177/0022034519882692.
- 16 Cahill DR, Marks SC.. Tooth eruption: evidence for the central role of the dental follicle. J Oral Pathol 1980; 9: 189-200 DOI: 10.1111/j.1600-0714.1980.tb00377.x.
- 17 Takahashi A, Nagata M, Gupta A. et al. Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption. Proceedings of the National Academy of Sciences 2019; 116: 575-580 DOI: 10.1073/pnas.1810200115.
- 18 Ono W, Sakagami N, Nishimori S. et al. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation. Nat Commun 2016; 7: 11277 DOI: 10.1038/ncomms11277.
- 19 Datta NS, Abou-Samra AB. PTH and PTHrP signaling in osteoblasts. Cell Signal 2009; 21: 1245-1254 DOI: 10.1016/j.cellsig.2009.02.012.
- 20 Roth H, Fritsche LG, Meier C. et al. Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption. Clin Oral Investig 2014; 18: 377-384 DOI: 10.1007/s00784-013-1014-3.
- 21 Kim BH, Pereverzev A, Zhu S. et al. Extracellular nucleotides enhance agonist potency at the parathyroid hormone 1 receptor. Cell Signal 2018; 46: 103-112 DOI: 10.1016/j.cellsig.2018.02.015.
- 22 Neer RM, Arnaud CD, Zanchetta JR. et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344: 1434-1441 DOI: 10.1056/nejm200105103441904.
- 23 Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005; 366: 1809-1820 DOI: 10.1016/s0140-6736(05)67728-8.
- 24 Neale Weitzmann M, Pacifici R. Parathyroid Diseases and T Cells. Curr Osteoporos Rep 2017; 15: 135-141 DOI: 10.1007/s11914-017-0359-y.
- 25 Grigoriadis AE, Schellander K, Wang ZQ. et al. Osteoblasts are target cells for transformation in c-fos transgenic mice. J Cell Biol 1993; 122: 685-701 DOI: 10.1083/jcb.122.3.685.
- 26 Sutkeviciute I, Vilardaga JP. Structural insights into emergent signaling modes of G protein-coupled receptors. J Biol Chem 2020; 295: 11626-11642 DOI: 10.1074/jbc.REV120.009348.
- 27 Sato T, Verma S, Khatri A et al. Comparable Initial Engagement of Intracellular Signaling Pathways by Parathyroid Hormone Receptor Ligands Teriparatide, Abaloparatide, and Long-Acting PTH. JBMR Plus 2021; 5: e10441. DOI: 10.1002/jbm4.10441
- 28 Hattersley G, Dean T, Corbin BA et al. Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology 2016; 157: 141–149. DOI: 10.1210/en.2015-1726
- 29 Lossdörfer S, Götz W, Jäger A. PTH(1-34)-induced changes in RANKL and OPG expression by human PDL cells modify osteoclast biology in a co-culture model with RAW 264.7 cells. Clin Oral Investig 2011; 15: 941-952 DOI: 10.1007/s00784-010-0456-0.
- 30 Wolf M, Jäger A, Abuduwali N. et al. Continuous PTH modulates alkaline phosphatase activity in human PDL cells via protein kinase C dependent pathways in vitro. Ann Anat 2013; 195: 455-460 DOI: 10.1016/j.aanat.2013.04.006.
- 31 Li Y, Hu Z, Zhou C. et al. Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the catabolic effects of mechanical strain in cementoblasts. BMC Cell Biology 2017; 18: 19 DOI: 10.1186/s12860-017-0133-0.
- 32 Chen B, Lin T, Yang X. et al. Intermittent parathyroid hormone (1-34) application regulates cAMP-response element binding protein activity to promote the proliferation and osteogenic differentiation of bone mesenchymal stromal cells, via the cAMP/PKA signaling pathway. Exp Ther Med 2016; 11: 2399-2406 DOI: 10.3892/etm.2016.3177.
- 33 Du L, Feng R, Ge S. PTH/SDF-1α cotherapy promotes proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells. Cell Prolif 2016; 49: 599-608 DOI: 10.1111/cpr.12286.
- 34 Pieles O, Reck A, Morsczeck C. High endogenous expression of parathyroid hormone-related protein (PTHrP) supports osteogenic differentiation in human dental follicle cells. Histochem Cell Biol 2020; 154: 397-403 DOI: 10.1007/s00418-020-01904-7.
- 35 Lyu P, Li B, Li P. et al. Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications. Frontiers in Cell and Developmental Biology 2021; 9 DOI: 10.3389/fcell.2021.654715.
- 36 Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res 2008; 87: 414-434 DOI: 10.1177/154405910808700509.
- 37 Jakob F, Müller-Deubert S, Ebert R. Teriparatid – Das molekulare und klinische Profil bei der Therapie der Osteoporose. Osteologie 2019; 28: 21-27
- 38 Pfeifer M. Neuer Wirkstoff Abaloparatid verhindert Knochenbrüche. Osteologie 2018; 27: 55-56 DOI: 10.1055/s-0038-1636980.
- 39 Zhang C, Li T, Zhou C. et al. Parathyroid hormone increases alveolar bone homoeostasis during orthodontic tooth movement in rats with periodontitis via crosstalk between STAT3 and β-catenin. International Journal of Oral Science 2020; 12: 38 DOI: 10.1038/s41368-020-00104-2.
- 40 Tokunaga K, Seto H, Ohba H. et al. Topical and intermittent application of parathyroid hormone recovers alveolar bone loss in rat experimental periodontitis. J Periodontal Res 2011; 46: 655-662 DOI: 10.1111/j.1600-0765.2011.01386.x.
- 41 Kim JH, Kim AR, Choi YH. et al. Intermittent PTH administration improves alveolar bone formation in type 1 diabetic rats with periodontitis. J Transl Med 2018; 16: 70 DOI: 10.1186/s12967-018-1438-2.
- 42 Poole KE, van Bezooijen R, Loveridge N. et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. Faseb j 2005; 19: 1842-1844 DOI: 10.1096/fj.05-4221fje.
- 43 Xu L, Mei L, Zhao R. et al. The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats. J Appl Oral Sci 2020; 28: e20190690 DOI: 10.1590/1678-7757-2019-0690.
- 44 Lu W, Li X, Yang Y. et al. PTH/PTHrP in controlled release hydrogel enhances orthodontic tooth movement by regulating periodontal bone remodaling. Journal of Periodontal Research 2021; 56: 885-896 DOI: 10.1111/jre.12885.