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Monogene Ionenkanalerkrankungen des Knochens

Monogenic ion channelopathies of the skeleton

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medizinische genetik

Zusammenfassung

Obwohl Ionenkanäle eher mit der Generierung von Aktionspotenzialen in Verbindung gebracht werden, können sie auch in unterschiedlichster Weise die Entwicklung und Funktion von Knochenzellen und -gewebe beeinflussen, was durch die hier vorgestellten Skeletterkrankungen verdeutlicht werden soll. Jeder der grundlegenden Zelltypen, Chondrozyten, Osteoblasten, Osteozyten, Osteoklasten, kann in die Pathogenese involviert sein und in vielen Fällen ist das Zusammenspiel der verschiedenen zellulären Defekte nicht verstanden. Connexin 43 und TRPV4, 2 der genannten Membranproteine, transportieren v. a. Kalzium und stehen jeweils mit einem Spektrum an Skelettphänotypen in Verbindung. Hierbei scheint Connexin 43 v. a. als Regulator in Osteoblasten und Osteozyten zu fungieren, während TRPV4 eine wichtige Rolle in Chondrozyten spielt. Die anderen beiden Beispiele sind die chloridtransportierenden Proteine ANO5 und ClC-7, deren Defekt die gnathodiaphysäre Dysplasie bzw. die Osteopetrose nach sich zieht. Während die Funktion von ANO5 noch unklar ist, konnte die Funktion von ClC-7 in Osteoklasten detailliert beschrieben werden.

Abstract

Although ion channels are intuitively more related to the generation of action potentials, they can influence skeletal cells, development, and homeostasis in different ways as demonstrated in this review. All major skeletal cell types, chondrocytes, osteoblasts, osteocytes, and osteoclasts, can be involved in the pathogenesis and often the interaction of these different defects is incompletely understood. Connexin 43 and TRPV4, two of the mentioned membrane proteins, predominantly conduct calcium ions and are the basis of a whole spectrum of skeletal phenotypes. While connexin 43 seems to regulate the function of osteoblasts and osteocytes, TRPV4 is crucial for chondrocytes. The other two examples are chloride-transporting membrane proteins ANO5 and ClC-7, which can cause gnathodiaphyseal dysplasia and osteopetrosis, respectively. Whereas the function of ANO5 is largely unknown, the role of ClC-7 in bone resorbing osteoclasts has been investigated in great detail.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. T. Stauber, D. Horn und U. Kornak geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Physiologie und Pathologie des Ionentransports, Max-Delbrück-Centrum für Molekulare Medizin (MDC) und Leibniz-Institut für Molekulare Pharmakologie (FMP) Berlin, Berlin, Deutschland

    T. Stauber

  2. Institut für Medizinische Genetik und Humangenetik, Charité-Universitaetsmedizin Berlin, Augustenburger Platz 1, 13351, Berlin, Deutschland

    D. Horn & U. Kornak

Authors
  1. T. Stauber
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  2. D. Horn
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  3. U. Kornak
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Correspondence to U. Kornak.

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Stauber, T., Horn, D. & Kornak, U. Monogene Ionenkanalerkrankungen des Knochens. medgen 25, 493–500 (2013). https://doi.org/10.1007/s11825-013-0420-x

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  • DOI: https://doi.org/10.1007/s11825-013-0420-x

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