The collagen receptor, discoidin domain receptor 2, functions in Gli1-positive skeletal progenitors and chondrocytes

Fatma F Mohamed1, Chunxi Ge1, Randy T Cowling2

  • 1Department of Periodontics & Oral Medicine, University of Michigan, Ann Arbor, MI, USA.

Bone Research
|February 10, 2022
PubMed

Insights

Discoidin Domain Receptor 2 (DDR2) is crucial for bone development. This study reveals DDR2’s essential role in skeletal progenitor cells and cartilage, impacting bone formation.

Area of Science:

  • Biochemistry
  • Developmental Biology
  • Cell Biology

Background:

  • Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor tyrosine kinase.
  • DDR2, along with integrins, mediates cellular responses to the extracellular matrix.
  • Loss-of-function mutations in DDR2 lead to severe skeletal growth and developmental defects in humans and mice.

Purpose of the Study:

  • To elucidate the cellular functions of DDR2 in bone development.
  • To investigate the role of DDR2 in skeletal progenitor cells and chondrocytes.

Main Methods:

  • Expression and lineage analysis of Ddr2 in bone.
  • Conditional deletion of Ddr2 in specific skeletal cell populations.
  • Analysis of chondrogenic and osteogenic differentiation potential.

Main Results:

  • DDR2 is selectively expressed in early bone formation stages, including resting zone and proliferating chondrocytes and periosteum.
  • DDR2-expressing cells can differentiate into chondrocytes, osteoblasts, and osteocytes and colocalize with the skeletal progenitor marker Gli1.
  • Conditional deletion of DDR2 in Gli1-positive skeletal progenitors and chondrocytes impairs skeletal development, while mature osteoblasts are unaffected.
  • DDR2 knockout inhibits chondrogenic and osteogenic differentiation in limb bud chondroprogenitors and marrow-derived skeletal progenitors, respectively.

Conclusions:

  • DDR2 plays a cell-autonomous role in skeletal progenitors and cartilage.
  • This collagen receptor is critical for normal skeletal development and bone formation.

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