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Informationen aus Orthodontie & Kieferorthopädie 2018; 50(03): 169-175
DOI: 10.1055/a-0648-8013
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© Georg Thieme Verlag KG Stuttgart · New York

Zahneruption und Zahnbewegung bei kongenitaler Retention mit Mutation des PTH1-Rezeptor-Gens

Defective Uncoupled Bone Modeling Pathway in Primary Failure of Eruption Type PTH1 Receptor Mutation During Tooth Eruption and Tooth Movement
Jan Danz
1   Klinik für Kieferorthopädie, Universität Bern, Bern, Schweiz
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Publication Date:
04 October 2018 (online)

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Zusammenfassung

Die primäre kongenitale Retention von Zähnen des Typs heterozygote Mutation von Parathyroid hormone receptor type 1 (PTH1R) mit autosomal dominanter Vererbung ist eine Regulationsstörung des Knochenumbaus, welche die Zahneruption und die Zahnbewegungen stark behindert oder verhindert. Bei beginnender Zahneruption und bei Zahnbewegung wird PTHrP (Parathyroid hormone-related protein) ausgeschüttet, welches durch Osteozyten den Knochenumbau Richtung Knochenresorption entkoppelt. Bei PTH1R-Mutation mit Funktionsverlust dieses Rezeptors fehlt einerseits die Verringerung der Osteoprotegerin (OPG)- und der Sclerostin-Ausschüttung durch Osteozyten und andererseits die erhöhte Expression und Ausschüttung von Soluble receptor activator of nuclear factor κB (sRANKL) durch Osteozyten und Osteoblasten, was zu einer ausbleibenden Osteoklastenaktivierung führt. Ohne Knochenresorption durch Osteoklasten sind sowohl die Zahneruption als auch die Zahnbewegung gestört. Durch das als kompetitiver Antagonist des wnt-Rezeptor-Komplexes (kanonischer-wnt-Signalweg) und der BMP-I/BMP-II-Rezeptoren wirkende Sclerostin modulieren Osteozyten auch die Osteoblastenaktivität. Bei Verdacht auf kongenitale Retention ist eine humangenetische Abklärung zum Test einer PTH1-Rezeptor-Mutation ein wichtiges diagnostisches Mittel, um nicht erfolgsversprechende kieferorthopädische Therapien zu vermeiden und Behandlungsalternativen planen zu können.

Abstract

Autosomal dominant inherited primary failure of eruption type PTH1R (Parathyroid hormone receptor type 1) mutation disrupts uncoupled bone modeling pathway resulting in defective tooth eruption and movement. PTHrP (Parathyroid hormone-related protein) uncouples bone remodeling towards resorption at initiation of tooth eruption and during tooth movement. In case of PTH1R-mutation with loss of function, down regulation of OPG (Osteoprotegerin) and decrease in Sclerostin secretion by osteocytes is lacking and, on the other hand, sRANKL (soluble receptor activator of nuclear factor κB) secretion by osteocytes and osteoblasts is not increased, resulting both in failure of osteoclast activation. Tooth eruption and tooth movement fails without bone resorption by osteoclasts. Osteocytes regulate osteoblast activity by sclerostin, which is a competitive antagonist of the Wnt-receptor-complex (Wnt/β-catenin pathway/canonical wnt pathway) and of BMP-I/BMP-II receptors. In case of suspected primary failure of eruption, human genetic testing of PTH1R mutation is an important diagnostic procedure to avoid unsuccessful orthodontic treatment and to evaluate alternative treatment options.

Schlüsselwörter

Kongenitale Retention - Knochen - Knochenumbau - Zahnbewegung - Zahneruption - PTH1-Rezeptor

Key words

primary failure of eruption - bone - bone remodeling - orthodontic tooth movement - tooth eruption - PTH1 receptor
 

  • Literatur

  • 1 Frazier-Bowers SA, Long S, Tucker M. Primary failure of eruption and other eruption disorders – Considerations for management by the orthodontist and oral surgeon. Semin Orthod 2016; 22: 34-44
    CrossrefPubMedGoogle Scholar
  • 2 Grover PS, Lorton L. The incidence of unerupted permanent teeth and related clinical cases. Oral Surg Oral Med Oral Pathol 1985; 59: 420-425
    CrossrefPubMedGoogle Scholar
  • 3 Baccetti T. Tooth anomalies associated with failure of eruption of first and second permanent molars. Am J Orthod Dentofacial Orthop 2000; 118: 608-610
    CrossrefPubMedGoogle Scholar
  • 4 Pilz P, Meyer-Marcotty P, Eigenthaler M. et al. Differential diagnosis of primary failure of eruption (PFE) with and without evidence of pathogenic mutations in the PTHR1 gene. J Orofac Orthop 2014; 75: 226-239
    CrossrefPubMedGoogle Scholar
  • 5 Bosker H, Kate ten LP, Nijenhuis LE. Familial reinclusion of permanent molars. Clin Genet 1978; 13: 314-320
    PubMedGoogle Scholar
  • 6 Proffit WR, Vig KW. Primary failure of eruption: a possible cause of posterior open-bite. Am J Orthod 1981; 80: 173-190
    CrossrefPubMedGoogle Scholar
  • 7 Dibiase AT. Primary failure of eruption in the permanent dentition of siblings. International Journal of Paediatric Dentistry 2000; 10: 153-157
    PubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Jelani M, Kang C, Mohamoud HSA. et al. A novel homozygous PTH1R variant identified through whole-exome sequencing further expands the clinical spectrum of primary failure of tooth eruption in a consanguineous Saudi family. Arch Oral Biol 2016; 67: 28-33
    CrossrefPubMedGoogle Scholar
  • 11 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: 1-16
    CrossrefPubMedGoogle Scholar
  • 12 Schipani E, Provot S. PTHrP, PTH and the PTH/PTHrP receptor in endochondral bone development. Birth Defects Res C Embryo Today 2003; 69: 352-362
    CrossrefPubMedGoogle Scholar
  • 13 Hanisch M, Hanisch L, Kleinheinz J. et al. Primary failure of eruption (PFE): a systematic review. Head Face Med 2018; 14: 1-9
    CrossrefPubMedGoogle Scholar
  • 14 Frazier-Bowers SA, Koehler KE, Ackerman JL. et al. Primary failure of eruption: further characterization of a rare eruption disorder. Am J Orthod Dentofacial Orthop 2007; 131: 1-11
    CrossrefPubMedGoogle Scholar
  • 15 Mosekilde L. Primary hyperparathyroidism and the skeleton. Clin Endocrinol 2008; 69: 1-19
    CrossrefPubMedGoogle Scholar
  • 16 Rogers A. Circulating osteoprotegerin and receptor activator for nuclear factor κB Ligand: Clinical Utility in Metabolic Bone Disease Assessment. Journal of Clinical Endocrinology & Metabolism 2005; 90: 6323-6331
    PubMedGoogle Scholar
  • 17 Furuya Y, Inagaki A, Khan M. et al. Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that possesses osteoclastogenesis inhibitory activity. J Biol Chem 2013; 288: 5562-5571
    CrossrefPubMedGoogle Scholar
  • 18 Honma M, Ikebuchi Y, Kariya Y. et al. Regulatory mechanisms of RANKL presentation to osteoclast precursors. Curr Osteoporos Rep 2014; 12: 115-120
    CrossrefPubMedGoogle Scholar
  • 19 Hauge EM, Qvesel D, Eriksen EF. et al. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 2001; 16: 1575-1582
    CrossrefPubMedGoogle Scholar
  • 20 Andersen TL, Sondergaard TE, Skorzynska KE. et al. A Physical mechanism for coupling bone resorption and formation in adult human bone. The American Journal of Pathology 2009; 174: 239-247
    CrossrefPubMedGoogle Scholar
  • 21 Matsuo K, Kuroda Y, Nango N. et al. Osteogenic capillaries orchestrate growth plate-independent ossification of the malleus. Development 2015; 142: 3912-3920
    CrossrefPubMedGoogle Scholar
  • 22 Heckt T, Keller J, Peters S. et al. Parathyroid hormone induces expression and proteolytic processing of Rankl in primary murine osteoblasts. Bone 2016; 92: 85-93
    CrossrefPubMedGoogle Scholar
  • 23 Divieti Pajevic P, Krause DS. Osteocyte regulation of bone and blood. Bone 2018; 2: 1-6
    PubMedGoogle Scholar
  • 24 Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003; 423: 337-342
    PubMedGoogle Scholar
  • 25 Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocrine Reviews 2008; 29: 155-192
    CrossrefPubMedGoogle Scholar
  • 26 Poole KES, van Bezooijen RL, Loveridge N. et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 2005; 19: 1842-1844
    CrossrefPubMedGoogle Scholar
  • 27 O'Brien CA, Plotkin LI, Galli C. et al. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS ONE 2008; 3: e2942 doi: 10.1371/journal.pone.0002942
    CrossrefPubMedGoogle Scholar
  • 28 Saini V, Marengi DA, Barry KJ. et al. Parathyroid hormone (PTH)/PTH-related peptide type 1 receptor (PPR) signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH. J Biol Chem 2013; 288: 20122-20134
    CrossrefPubMedGoogle Scholar
  • 29 Lin C, He L. Sclerostin inhibits bone growth via antagonizing Wnt/beta-catenin signaling, and via stimulating cell death. Bone 2008; 43: 30
    PubMedGoogle Scholar
  • 30 Winkler DG, Sutherland MK, Geoghegan JC. et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. The EMBO Journal 2003; 22: 6267-6276
    CrossrefPubMedGoogle Scholar
  • 31 Shi C, Iura A, Terajima M. et al. Deletion of BMP receptor type IB decreased bone mass in association with compromised osteoblastic differentiation of bone marrow mesenchymal progenitors. Scientific Reports 2016; 6: 1-13
    CrossrefPubMedGoogle Scholar
  • 32 Alberts B, Johnson A, Lewis J. et al. Molecular Biology of the cell. Fifth Edition New York: Garland Science; 2008
    Google Scholar
  • 33 Skerry TM. The response of bone to mechanical loading and disuse: Fundamental principles and influences on osteoblast/osteocyte homeostasis. Archives of Biochemistry and Biophysics 2008; 473: 117-123
    CrossrefPubMedGoogle Scholar
  • 34 Morse A, Schindeler A, McDonald MM. et al. Sclerostin antibody augments the anabolic bone formation response in a mouse model of mechanical tibial loading. J Bone Miner Res 2018; 33: 486-498
    CrossrefPubMedGoogle Scholar
  • 35 Arnsdorf EJ, Tummala P, Jacobs CR. Non-canonical wnt signaling and N-Cadherin related β-Catenin aignaling play a role in mechanically induced osteogenic cell fate. PLoS ONE 2009; 4: 1-10
    CrossrefPubMedGoogle Scholar
  • 36 Batra N, Burra S, Siller-Jackson AJ. et al. Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels. Proc Natl Acad Sci USA 2012; 109: 3359-3364
    CrossrefPubMedGoogle Scholar
  • 37 Honma M, Ikebuchi Y, Kariya Y. et al. Establishment of optimized in vitro assay methods for evaluating osteocyte functions. J Bone Miner Metab 2015; 33: 73-84
    CrossrefPubMedGoogle Scholar
  • 38 Ansari N, Ho PW, Crimeen-Irwin B. et al. Autocrine and paracrine regulation of the murine skeleton by osteocyte-derived parathyroid hormone-related protein. J Bone Miner Res 2017; 33: 137-153
    PubMedGoogle Scholar
  • 39 Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res 2008; 87: 414-434
    CrossrefPubMedGoogle Scholar
  • 40 Philbrick WM, Dreyer BE, Nakchbandi IA. et al. Parathyroid hormone-related protein is required for tooth eruption. Proc Natl Acad Sci USA 1998; 95: 11846-11851
    CrossrefPubMedGoogle Scholar
  • 41 Carollo DA, Hoffman RL, Brodie AG. Histology and function of dental Gubernacular Cord. Angle Orthod 1971; 41: 300-307
    PubMedGoogle Scholar
  • 42 Frazier-Bowers SA, Hendricks HM, Wright JT. et al. Novel mutations in PTH1R associated with primary failure of eruption and osteoarthritis. J Dent Res 2013; 93: 134-139
    PubMedGoogle Scholar
  • 43 Wise GE, Lumpkin SJ, Huang H. et al. Osteoprotegerin and osteoclast differentiation factor in tooth eruption. J Dent Res 2000; 79: 1937-1942
    PubMedGoogle Scholar
  • 44 Schroeder HE. Orale Strukturbiologie. Stuttgart: Thieme; 2000
    Google Scholar
  • 45 Li M, Yi J, Yang Y. et al. Investigation of optimal orthodontic force at the cellular level through three-dimensionally cultured periodontal ligament cells. Europ J Orthod 2016; 38: 366-372
    CrossrefPubMedGoogle Scholar
  • 46 Kennedy OD, Herman BC, Laudier DM. et al. Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. Bone 2012; 50: 1115-1122
    CrossrefPubMedGoogle Scholar
  • 47 Danz JC, Bibby BM, Katsaros C. et al. Effects of facial tooth movement on the periodontium in rats: a comparison between conventional and low force. J Clin Periodontol 2016; 43: 229-237
    CrossrefPubMedGoogle Scholar
  • 48 Danz JC, Dalstra M, Bosshardt DD. et al. A rat model for orthodontic translational expansive tooth movement. Orthod Craniofac Res 2013; 16: 223-233
    PubMedGoogle Scholar
  • 49 Wise GE, Frazier-Bowers S, D'Souza RN. Cellular, molecular, and genetic determinants of tooth eruption. Crit Rev Oral Biol Med 2002; 13: 323-334
    CrossrefPubMedGoogle Scholar