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

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

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