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

Autor: Chou Liang-Yin, Chung-Hwan Chen, Yin-Chih Fu, Shu-Chun Chuang, Yan-Hsiung Wang, Chau-Zen Wang, Yi-Hsiung Lin, Hsin-Chiao Chou, Tsung Lin Cheng
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Bone Morphogenetic Protein 2
Core Binding Factor Alpha 1 Subunit
p38 Mitogen-Activated Protein Kinases
bone
lcsh:Chemistry
Mice
0302 clinical medicine
DDR1
Femur
Phosphorylation
lcsh:QH301-705.5
Spectroscopy
Mice
Knockout
Chemistry
Gene Expression Regulation
Developmental
Osteoblast
General Medicine
Computer Science Applications
RUNX2
medicine.anatomical_structure
bone development
030220 oncology & carcinogenesis
osteoblast
Collagen
medicine.symptom
Cancellous bone
musculoskeletal diseases
medicine.medical_specialty
animal structures
Bone morphogenetic protein 2
Catalysis
Article
osteogenesis
Inorganic Chemistry
03 medical and health sciences
Internal medicine
medicine
Animals
Physical and Theoretical Chemistry
Molecular Biology
Osteoblasts
Ossification
Receptors
Dopamine D1
Organic Chemistry
Alkaline Phosphatase
discoidin domain receptor 1
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
Cortical bone
Discoidin domain
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 7210, p 7210 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 19
ISSN: 1661-6596
1422-0067
Popis: 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 (OKO&Delta
Ddr1) 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, OKO&Delta
Ddr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKO&Delta
Ddr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1f/f-4OHT mice. In femurs of 4-week-old OKO&Delta
Ddr1 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.
Databáze: OpenAIRE
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