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

Bo Shen, Kristy Vardy, Payton Hughes, Alpaslan Tasdogan, Zhiyu Zhao, Rui Yue, Genevieve M. Crane, Sean J Morrison

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jan 11 2019

Keywords

  • bone
  • integrin
  • mouse
  • osteogenesis
  • Osteolectin
  • regenerative medicine
  • skeletal stem cell
  • stem cells
  • Wnt signaling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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