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Updated: Oct 4, 2025

Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis
Published on: December 18, 2019
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.
Abstract:
Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor kinase that, together with integrins, is required for cells to respond to the extracellular matrix. Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development. However, the cellular functions of Ddr2 in bone are not understood. Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum. Consistent with these findings, Ddr2+ cells could differentiate into hypertrophic chondrocytes, osteoblasts, and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker, Gli1. A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts. Furthermore, Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation, respectively. This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.
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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