Discoidin Domain Receptor 1 Regulates Runx2 during Osteogenesis of Osteoblasts and Promotes Bone Ossification via Phosphorylation of p38

• Published in: International journal of molecular sciences 2020-10, Vol.21 (19), p.7210
• Main Authors: Chou, Liang-Yin, Chen, Chung-Hwan, Chuang, Shu-Chun, Cheng, Tsung-Lin, Lin, Yi-Hsiung, Chou, Hsin-Chiao, Fu, Yin-Chih, Wang, Yan-Hsiung, Wang, Chau-Zen
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - genetics; Animals; Apoptosis; Biomedical materials; Body length; Body weight; Bone density; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - genetics; Bones; Cancellous bone; Cartilage; Cbfa-1 protein; Collagen; Collagen - genetics; Computed tomography; Core Binding Factor Alpha 1 Subunit - genetics; Cortical bone; Domains; Dopamine D1 receptors; Dwarfism; Femur - growth & development; Femur - metabolism; Gene expression; Gene Expression Regulation, Developmental - genetics; Kinases; Mechanical properties; Membrane proteins; Mice; Mice, Knockout; Mineralization; Ossification; Osteoblastogenesis; Osteoblasts; Osteoblasts - metabolism; Osteocytes; Osteogenesis; Osteogenesis - genetics; p38 Mitogen-Activated Protein Kinases - genetics; Phosphorylation; Phosphorylation - genetics; Physiological aspects; Proteins; Receptors, Dopamine D1 - genetics; Rodents
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197210

Discoidin domain receptor 1 ( ) is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific knockout (OKOΔ ) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control mice. We hypothesize that regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old mice, OKOΔ mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKOΔ mice, resulting in decreased mechanical properties of femurs compared with those of mice. In femurs of 4-week-old OKOΔ mice, H&E staining showed fewer osteocytes and decreased cortical bone thickness than . Osteoblast differentiation markers, including BMP2, Runx2, alkaline phosphatase (ALP), Col-I and OC, were decreased compared with those of control mice. 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 in osteoblasts demonstrated that DDR1 mediates the expression and activity of Runx2 and the downstream osteogenesis markers during osteogenesis through regulation of p38 phosphorylation.