scholarly journals Increased expression of the collagen receptor discoidin domain receptor 2 in articular cartilage as a key event in the pathogenesis of osteoarthritis

2007 ◽  
Vol 56 (8) ◽  
pp. 2663-2673 ◽  
Author(s):  
Lin Xu ◽  
Haibing Peng ◽  
Sonya Glasson ◽  
Peter L. Lee ◽  
Kenpan Hu ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor

Role of Discoidin Domain Receptor 2 in Craniofacial Bone Regeneration

2021 ◽  
pp. 002203452110074
Author(s):  
A. Binrayes ◽  
C. Ge ◽  
F.F. Mohamed ◽  
R.T. Franceschi
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Congenital Defects ◽  
Calvarial Bone ◽  
Discoidin Domain Receptor ◽  
Skeletal Defects ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor ◽  
Deficient Mice

Bone loss caused by trauma, neoplasia, congenital defects, or periodontal disease is a major cause of disability and human suffering. Skeletal progenitor cell–extracellular matrix interactions are critical for bone regeneration. Discoidin domain receptor 2 (DDR2), an understudied collagen receptor, plays an important role in skeletal development. Ddr2 loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, including altered cranial shape, dwarfing, reduced trabecular and cortical bone, alveolar bone/periodontal defects, and altered dentition. However, the role of this collagen receptor in craniofacial regeneration has not been examined. To address this, calvarial subcritical-size defects were generated in wild-type (WT) and Ddr2-deficient mice. The complete bridging seen in WT controls at 4 wk postsurgery was not observed in Ddr2-deficient mice even after 12 wk. Quantitation of defect bone area by micro–computed tomography also revealed a 50% reduction in new bone volume in Ddr2-deficient mice. Ddr2 expression during calvarial bone regeneration was measured using Ddr2-LacZ knock-in mice. Expression was restricted to periosteal surfaces of uninjured calvarial bone and, after injury, was detected in select regions of the defect site by 3 d postsurgery and expanded during the healing process. The impaired bone healing associated with Ddr2 deficiency may be related to reduced osteoprogenitor or osteoblast cell proliferation and differentiation since knockdown/knockout of Ddr2 in a mesenchymal cell line and primary calvarial osteoblast cultures reduced osteoblast differentiation while Ddr2 overexpression was stimulatory. In conclusion, Ddr2 is required for cranial bone regeneration and may be a novel target for therapy.

scholarly journals Intact Pericellular Matrix of Articular Cartilage Is Required for Unactivated Discoidin Domain Receptor 2 in the Mouse Model

2011 ◽  
Vol 179 (3) ◽  
pp. 1338-1346 ◽  
Author(s):  
Lin Xu ◽  
Ilona Polur ◽  
Jacqueline M. Servais ◽  
Sirena Hsieh ◽  
Peter L. Lee ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mouse Model ◽  
Pericellular Matrix ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2

scholarly journals Discoidin domain receptor 2 germline gene deletion leads to altered heart structure and function in the mouse

2014 ◽  
Vol 307 (5) ◽  
pp. H773-H781 ◽  
Author(s):  
Randy T. Cowling ◽  
Seon Ju Yeo ◽  
In Jai Kim ◽  
Joong Il Park ◽  
Yusu Gu ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Structure And Function ◽  
The Body ◽  
Collagen Deposition ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2 ◽  
And Function ◽  
Collagen Receptor

Discoidin domain receptor 2 (DDR2) is a fibrillar collagen receptor that is expressed in mesenchymal cells throughout the body. In the heart, DDR2 is selectively expressed on cardiac fibroblasts. We generated a germline DDR2 knockout mouse and used this mouse to examine the role of DDR2 deletion on heart structure and function. Echocardiographic measurements from null mice were consistent with those from a smaller heart, with reduced left ventricular chamber dimensions and little change in wall thickness. Fractional shortening appeared normal. Left ventricular pressure measurements revealed mild inotropic and lusitropic abnormalities that were accentuated by dobutamine infusion. Both body and heart weights from 10-wk-old male mice were ∼20% smaller in null mice. The reduced heart size was not simply due to reduced body weight, since cardiomyocyte lengths were atypically shorter in null mice. Although normalized cardiac collagen mass (assayed by hydroxyproline content) was not different in null mice, the collagen area fraction was statistically higher, suggesting a reduced collagen density from altered collagen deposition and cross-linking. Cultured cardiac fibroblasts from null mice deposited collagen at a slower rate than wild-type littermates, possibly due to the expression of lower prolyl 4-hydroxylase α-isoform 1 enzyme levels. We conclude that genetic deletion of the DDR2 collagen receptor alters cardiac fibroblast function. The resulting perturbations in collagen deposition can influence the structure and function of mature cardiomyocytes.

scholarly journals The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis

2013 ◽  
Vol 15 (6) ◽  
pp. 677-687 ◽  
Author(s):  
Kun Zhang ◽  
Callie A. Corsa ◽  
Suzanne M. Ponik ◽  
Julie L. Prior ◽  
David Piwnica-Worms ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Discoidin Domain Receptor ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor
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