Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization

Abstract Objective The present study aimed to determine the role of the discoidin domain receptor 2 (DDR2) in the osteonectin (ON) regulation of osteoblast mineralization through the activation of p38 mitogen-activated protein kinase (MAPK). Methods Four groups were established: the ON group, the in...

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Main Authors: Yun-Sen Zhu, Jiang-Nan Zhang, Ting-Ting Mo, Chang Jiang, Ru-Chao Ma, Liang Chen
Format: Article
Language:English
Published: BMC 2021-12-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-021-02860-1
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author Yun-Sen Zhu
Jiang-Nan Zhang
Ting-Ting Mo
Chang Jiang
Ru-Chao Ma
Liang Chen
author_facet Yun-Sen Zhu
Jiang-Nan Zhang
Ting-Ting Mo
Chang Jiang
Ru-Chao Ma
Liang Chen
author_sort Yun-Sen Zhu
collection DOAJ
description Abstract Objective The present study aimed to determine the role of the discoidin domain receptor 2 (DDR2) in the osteonectin (ON) regulation of osteoblast mineralization through the activation of p38 mitogen-activated protein kinase (MAPK). Methods Four groups were established: the ON group, the inhibitor group, the Ddr2-small interfering ribonucleic acid (siRNA) group, and the control group. Osteoblasts from the parietal bones of neonatal Sprague–Dawley rats were isolated and cultured. In the ON group, 1 µg/mL ON was added to the osteoblasts. The gene expressions of collagen 1 (Col 1) and Ddr2 were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In the inhibitor group, the osteoblasts were added to WRG-28 (a specific DDR2 inhibitor), and in the Ddr2-siRNA group, the osteoblasts were transfected with Ddr2-siRNA. The gene and protein expressions of DDR2, bone sialoprotein, osteocalcin, osteopontin, and p38 MAPK were determined using RT-qPCR and western blot analysis. Alizarin red staining and transmission electron microscopy were used to detect mineralization. Results The results showed that ON enhanced the osteoblast Col 1 and Ddr2 gene expressions, while the use of a Ddr2-siRNA/DDR2-blocker decreased the OPN, BSP, OCN, and P38 gene and protein expressions and reduced osteoblast cellular activity and mineralized nodules. Conclusion The present study demonstrated that DDR2 activation of p38 MAPK is an important approach to ON-regulating osteoblast mineralization.
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spelling doaj.art-c02c3e6261414b0394c2d9016e0809332022-12-22T04:28:21ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-12-0116111110.1186/s13018-021-02860-1Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralizationYun-Sen Zhu0Jiang-Nan Zhang1Ting-Ting Mo2Chang Jiang3Ru-Chao Ma4Liang Chen5Department of Orthopaedic Surgery, The First People’s Hospital of WenlingDepartment of Orthopaedic Surgery, The First People’s Hospital of WenlingDepartment of Orthopaedic Surgery, The First People’s Hospital of WenlingDepartment of Orthopaedic Surgery, The First People’s Hospital of WenlingDepartment of Orthopaedic Surgery, The First People’s Hospital of WenlingDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Soochow UniversityAbstract Objective The present study aimed to determine the role of the discoidin domain receptor 2 (DDR2) in the osteonectin (ON) regulation of osteoblast mineralization through the activation of p38 mitogen-activated protein kinase (MAPK). Methods Four groups were established: the ON group, the inhibitor group, the Ddr2-small interfering ribonucleic acid (siRNA) group, and the control group. Osteoblasts from the parietal bones of neonatal Sprague–Dawley rats were isolated and cultured. In the ON group, 1 µg/mL ON was added to the osteoblasts. The gene expressions of collagen 1 (Col 1) and Ddr2 were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In the inhibitor group, the osteoblasts were added to WRG-28 (a specific DDR2 inhibitor), and in the Ddr2-siRNA group, the osteoblasts were transfected with Ddr2-siRNA. The gene and protein expressions of DDR2, bone sialoprotein, osteocalcin, osteopontin, and p38 MAPK were determined using RT-qPCR and western blot analysis. Alizarin red staining and transmission electron microscopy were used to detect mineralization. Results The results showed that ON enhanced the osteoblast Col 1 and Ddr2 gene expressions, while the use of a Ddr2-siRNA/DDR2-blocker decreased the OPN, BSP, OCN, and P38 gene and protein expressions and reduced osteoblast cellular activity and mineralized nodules. Conclusion The present study demonstrated that DDR2 activation of p38 MAPK is an important approach to ON-regulating osteoblast mineralization.https://doi.org/10.1186/s13018-021-02860-1Osteonectinp38 MAPK signaling pathwayDiscoidin domain receptor 2Mineralization
spellingShingle Yun-Sen Zhu
Jiang-Nan Zhang
Ting-Ting Mo
Chang Jiang
Ru-Chao Ma
Liang Chen
Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization
Journal of Orthopaedic Surgery and Research
Osteonectin
p38 MAPK signaling pathway
Discoidin domain receptor 2
Mineralization
title Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization
title_full Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization
title_fullStr Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization
title_full_unstemmed Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization
title_short Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization
title_sort discoidin domain receptor 2 activation of p38 mitogen activated protein kinase as an important pathway for osteonectin regulating osteoblast mineralization
topic Osteonectin
p38 MAPK signaling pathway
Discoidin domain receptor 2
Mineralization
url https://doi.org/10.1186/s13018-021-02860-1
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