Integrin alpha11 is an Osteolectin receptor and is required for the maintenance of adult skeletal bone mass

• DOI: 10.7554/elife.42274
• Publication Date: 2019-01-11T13:00:17Z
• Authors: Bo Shen; Kristy Vardy; Payton Hughes; Alpaslan Tasdogan; Zhiyu Zhao; Rui Yue; Genevieve M Crane; Sean J Morrison
• Keywords: 0301 basic medicine; integrin; QH301-705.5; Science; Medizin; Mice, Transgenic; bone; osteogenesis; Cell Line; 03 medical and health sciences; Osteogenesis; Animals; Humans; Amino Acid Sequence; Biology (General); skeletal stem cell; Mice, Knockout; Osteoblasts; Sequence Homology, Amino Acid; Stem Cells; Q; R; Cell Differentiation; Mesenchymal Stem Cells; Wnt signaling; Stem Cells and Regenerative Medicine; Medicine; Receptors, Leptin; Osteolectin; Integrin alpha Chains

We previously discovered a new osteogenic growth factor that is required to maintain adult skeletal bone mass, Osteolectin/Clec11a. Osteolectin acts on Leptin Receptor+ (LepR+) stem cells and other progenitors in marrow promote their differentiation into osteoblasts. Here we identify receptor for Osteolectin, integrin α11, which expressed by LepR+ α11β1 binds with nanomolar affinity the response Osteolectin. Deletion of Itga11 (which encodes α11) from mouse human stromal impaired blocked Like deficient mice, Lepr-cre; Itga11fl/fl mice appeared grossly normal but exhibited reduced osteogenesis accelerated loss during adulthood. binding promoted Wnt pathway activation, was necessary This reveals mechanism maintenance mass: activation Osteolectin/α11β1 signaling.