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Open AccessArticle

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

by 1,2,3, 2,3,4,5,6,7, 2,3, 2,8,9,10, 11,12,13, 1,2,3, 1,2,3,4, 2,14 and 1,2,3,9,10,*
1
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
2
Orthopaedic Research Centre, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
3
Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
4
Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
5
Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan
6
Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
7
Division of Adult Reconstruction Surgery, Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
8
Cardiovascular Research Centre, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan
9
Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
10
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
11
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
12
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
13
Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
14
School of Dentistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7210; https://doi.org/10.3390/ijms21197210
Received: 14 September 2020 / Revised: 25 September 2020 / Accepted: 26 September 2020 / Published: 29 September 2020
(This article belongs to the Special Issue Bone Development and Regeneration)
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 (OKOΔDdr1) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control Ddr1f/f-4OHT mice. We hypothesize that Ddr1 regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old Ddr1f/f-4OHT mice, OKOΔDdr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKOΔDdr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1f/f-4OHT mice. In femurs of 4-week-old OKOΔDdr1 mice, H&E staining showed fewer osteocytes and decreased cortical bone thickness than Ddr1f/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. View Full-Text
Keywords: bone; discoidin domain receptor 1; DDR1; osteoblast; osteogenesis; bone development bone; discoidin domain receptor 1; DDR1; osteoblast; osteogenesis; bone development
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MDPI and ACS Style

Chou, L.-Y.; Chen, C.-H.; Chuang, S.-C.; Cheng, T.-L.; Lin, Y.-H.; Chou, H.-C.; Fu, Y.-C.; Wang, Y.-H.; Wang, C.-Z. Discoidin Domain Receptor 1 Regulates Runx2 during Osteogenesis of Osteoblasts and Promotes Bone Ossification via Phosphorylation of p38. Int. J. Mol. Sci. 2020, 21, 7210.

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