Human recessive osteopetrosis

Summary

Osteopetrosis is an inherited high bone mass condition resulting from reduced osteoclast activity. Over the past ten years, many of the genes mutated in the various forms of osteopetrosis have been identified. It has become clear that there are not only dominant and recessive forms, but also that within the recessive forms subsets exist, classified as osteoclast-rich and osteoclast-poor. Here, we review the different genetic mutations that are known to cause osteopetrosis and then focus specifically on recessive types of the disease. We will illustrate how not only genetic analysis is important, but also that functional osteoclast assays in the laboratory, combined with bone histology, can help to come to a precise diagnosis. We then discuss how this rare condition has led to new insights in the complex process of bone resorption by osteoclasts. Our story is one of bedside to bench and back again.

Zusammenfassung

Bei der Osteopetrose handelt es sich um eine erblich bedingte erhebliche Zunahme der Knochenmasse infolge einer verminderten Osteoklastenaktivität. In den vergangenen zehn Jahren wurde eine Reihe von Genmutationen bei den verschiedenen Osteopetrose-Formen identifiziert. Es wurde klar, dass es nicht nur dominant und rezessiv vererbte Formen gibt, sondern dass innerhalb der rezessiven Formen Untergruppen existieren, die als osteoklastenreich und osteoklastenarm klassifiziert werden. In diesem Übersichtsartikel werden die verschiedenen bei Osteopetrose bekannten Genmutationen, mit besonderer Berücksichtigung der rezessiven Erkrankungsformen, dargestellt. Es wird gezeigt, dass nicht nur die genetische Analyse von Bedeutung ist, sondern dass auch ein funktionales Osteoklasten-Assay im Labor, kombiniert mit einer histologischen Untersuchung der Knochen, eine exakte Diagnosestellung erleichtern kann. Anschließend wird diskutiert, wie diese seltene Erkrankung zu neuen Einblicken in den komplexen Prozess der Knochenresorption durch Osteoklasten geführt hat. Es ist die Geschichte einer Entwicklung von der Klinik zur Molekulargenetik und wieder zurück.

Keywords

Osteopetrosis - osteoclast - acidification - endosomal trafficking

Schlüsselwörter

Osteopetrose - Osteoklast - Azidose - endosomaler Transport

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