Sklerostin des Osteozyten – von der Expression zur klinischen Anwendung

Zusammenfassung

Sklerostin ist ein sezerniertes Glykoprotein und ein Produkt des SOST-Gens, welches im Knochen vorranging von Osteozyten exprimiert wird und zu einer Inhibition der Osteoblasten-induzierten Knochenformation und damit zu einer reduzierten Knochenmasse führen kann. Im Gegensatz dazu induziert eine Funktionsdeletion des SOST-Gens einen High-bone-mass-Knochenphänotyp. Darüber hinaus wirkt Sklerostin auf den Osteozyten selbst, wodurch der Osteoklasten-gesteuerte Knochenabbau gefördert werden kann und die osteozytäre Osteolyse unterstützt wird. Die Sklerostin-Expression kann durch verschiedene Mechanismen beeinflusst werden und bildet aufgrund der anabolen Rolle in der Knochenformation einen potenziellen Behandlungsansatz. Der Sklerostin-Antikörper Romosozumab ist seit Anfang 2019 in Japan und den USA zugelassen, und es zeigen sich erste positive Ergebnisse bei der Behandlung postmenopausaler Osteoporose. Andere Studien präsentieren Daten zu Sklerostin-Serumwerten in Relation zu Frakturraten oder Erkrankungen wie Diabetes mellitus Typ 2, lassen jedoch die Frage offen, ob sich Sklerostin als Biomarker in der Frakturrisikodiagnostik eignet.

Abstract

Sclerostin is a secreted glycoprotein and a product of the SOST gene, which is primarily expressed in osteocytes. Expression of sclerostin leads to inhibition of osteoblast-induced bone formation and therefore to reduced bone mass. In contrast, the loss-of-function deletion of the SOST gene induces a high bone mass bone phenotype. Furthermore, sclerostin may act on the osteocyte itself which leads to an increased osteoclast-induced bone resorption and supports osteocytic osteolysis. Sclerostin expression can be influenced by different mechanisms and represents a potential treatment option based on the anabolic action in bone formation. The sclerostin antibody Romosozumab is available since the beginning of 2019 in Japan and the US and first studies have shown positive effects on fracture risk and BMD in postmenopausal women. Other studies present data on sclerostin serum values in correlation with fractures and diseases such as diabetes mellitus type 2 which leave the unanswered question whether sclerostin is a possible biomarker for fracture risk diagnostics.

Schlüsselwörter

Sklerostin - Osteozyt - Wnt-Singaltransduktionsweg - Mechanosensation

Keywords

Sclerostin - osteocyte - Wnt-signalling pathway - mechanosensation

Publication History

Received: 11 October 2019

Accepted: 26 November 2019

Article published online:
25 February 2020

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