Journal article

Reversing LRP5-Dependent Osteoporosis and SOST Deficiency-Induced Sclerosing Bone Disorders by Altering WNT Signaling Activity

Ming-Kang Chang, Ina Kramer, Hansjoerg Keller, Jonathan H Gooi, Corinne Collett, David Jenkins, Seth A Ettenberg, Feng Cong, Christine Halleux, Michaela Kneissel

JOURNAL OF BONE AND MINERAL RESEARCH | WILEY | Published : 2014

Abstract

The bone formation inhibitor sclerostin encoded by SOST binds in vitro to low-density lipoprotein receptor-related protein (LRP) 5/6 Wnt co-receptors, thereby inhibiting Wnt/β-catenin signaling, a central pathway of skeletal homeostasis. Lrp5/LRP5 deficiency results in osteoporosis-pseudoglioma (OPPG), whereas Sost/SOST deficiency induces lifelong bone gain in mice and humans. Here, we analyzed the bone phenotype of mice lacking Sost (Sost(-/-) ), Lrp5 (Lrp5(-/-) ), or both (Sost(-/-) ;Lrp5(-/-) ) to elucidate the mechanism of action of Sost in vivo. Sost deficiency-induced bone gain was significantly blunted in Sost(-/-) ;Lrp5(-/-) mice. Yet the Lrp5 OPPG phenotype was fully rescued in Sost..

View full abstract

University of Melbourne Researchers