Clec11a/osteolectin is an osteogenic growth factor that promotes the maintenance of the adult skeleton

Elife. 2016 Dec 13;5:e18782. doi: 10.7554/eLife.18782.

Abstract

Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin.

Keywords: developmental biology; mouse; osteogenesis; osteoporosis; skeletal stem cells; stem cells.

MeSH terms

  • Adult
  • Animals
  • Cell Differentiation*
  • Cells, Cultured
  • Hematopoietic Cell Growth Factors / deficiency
  • Hematopoietic Cell Growth Factors / genetics
  • Hematopoietic Cell Growth Factors / metabolism*
  • Humans
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Osteogenesis*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Skeleton / physiology*

Substances

  • CLEC11A protein, human
  • Clec11A protein, mouse
  • Hematopoietic Cell Growth Factors
  • Lectins, C-Type
  • Recombinant Proteins