Discoidin Domain Receptors (DDRs) are unique members of the Receptor Tyrosine Kinases (RTKs) family. Most RTKs are activated by soluble proteins present in bodily fluids, however DDRs are activated by the extracellular matrix (ECM) protein, collagen. Collagen fiber assembly is a tightly controlled process affecting many physiological processes. DDR expression and activation plays a crucial role in collagen assembly, ECM remodeling, cell adhesion and proliferation.
Our earlier studies established a unique mechanism of collagen regulation by DDR2 extracellular domain (ECD). This work further investigates how DDR1 ECD and DDR2 ECD affects collagen fibrillogenesis. Mouse osteoblast cell lines stably or transiently over-expressing DDR1 or DDR2 ECD were utilized. Transmission electron microscopy, fluorescence microscopy, and hydroxyproline assays demonstrated that DDR ECD expression reduced the rate and quantity of collagen deposition and significantly altered fiber morphology. Collectively, our studies advanced our understanding of DDRs as powerful regulators of collagen deposition in the ECM.