| First Author | Chou LY | Year | 2020 |
| Journal | Int J Mol Sci | Volume | 21 |
| Issue | 19 | PubMed ID | 33003599 |
| Mgi Jnum | J:303490 | Mgi Id | MGI:6514462 |
| Doi | 10.3390/ijms21197210 | Citation | Chou LY, et al. (2020) Discoidin Domain Receptor 1 Regulates Runx2 during Osteogenesis of Osteoblasts and Promotes Bone Ossification via Phosphorylation of p38. Int J Mol Sci 21(19):7210 |
| abstractText | Discoidin domain receptor 1 (Drd1) is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific Ddr1 knockout (OKODeltaDdr1) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control Ddr1(f/f-4OHT) mice. We hypothesize that Ddr1 regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old Ddr1(f/f-4OHT) mice, OKODeltaDdr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKODeltaDdr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1(f/f-4OHT) mice. In femurs of 4-week-old OKODeltaDdr1 mice, H&E staining showed fewer osteocytes and decreased cortical bone thickness than Ddr1(f/f-4OHT). Osteoblast differentiation markers, including BMP2, Runx2, alkaline phosphatase (ALP), Col-I and OC, were decreased compared with those of control mice. Ddr1 knockdown in osteoblasts resulted in decreased mineralization, ALP activity, phosphorylated p38 and protein levels of BMP2, Runx2, ALP, Col-I and OC during osteogenesis. Overexpression and knockdown of Ddr1 in osteoblasts demonstrated that DDR1 mediates the expression and activity of Runx2 and the downstream osteogenesis markers during osteogenesis through regulation of p38 phosphorylation. |
