Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels

• DOI: 10.1073/pnas.1413828111
• Publication Date: 2014-11-20T08:43:24Z
• Authors: Ming-Kang Chang; Ina Kramer; Thomas Huber; Bernd Kinzel; Sabine Guth-Gundel; Olivier Leupin; Michaela Kneissel
• Keywords: Sclerostin; Cancellous bone; Osteocyte

Significance Targeting WNT (Wingless-type)/β-catenin signaling has emerged as an attractive novel therapeutic approach to the treatment of bone diseases. We previously identified LRP4 (low-density lipoprotein receptor-related protein 4) a facilitator action antagonist SOST/sclerostin in vitro. Here, we generated bone-specific Lrp4 -deficient mouse lines and anti-LRP4 antibodies selectively disrupting sclerostin function. Using these genetic pharmacological tools, demonstrate that disruption function induces gain vivo results highly elevated circulating levels. Together, findings provide important insights into role key regulator homeostasis mode new strategy for promoting through targeting pathway.