Induction of Lrp5 HBM-causing mutations in Cathepsin-K expressing cells alters bone metabolism

High-bone-mass (HBM)-causing missense mutations in the low density lipoprotein receptor-related protein-5 (Lrp5) are associated with increased osteoanabolic action and protection from disuse- and ovariectomy-induced osteopenia. These mutations (e.g., A214V and G171V) confer resistance to endogenous secreted Lrp5/6 inhibitors, such as sclerostin (SOST) and Dickkopf homolog-1 (DKK1). Cells in the osteoblast lineage are responsive to canonical Wnt stimulation, but recent work has indicated that osteoclasts exhibit both indirect and direct responsiveness to canonical Wnt.

Source: Bone - October 25, 2018 Category: Orthopaedics Authors: Kyung Shin Kang, Jung Min Hong, Daniel J. Horan, Kyung-Eun Lim, Whitney A. Bullock, Angela Bruzzaniti, Steven Hann, Matthew L. Warman, Alexander G. Robling Tags: Full Length Article Source Type: research