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

J Orthop Surg Res. 2021 Dec 7;16(1):711. doi: 10.1186/s13018-021-02860-1.

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.

Keywords: Discoidin domain receptor 2; Mineralization; Osteonectin; p38 MAPK signaling pathway.

MeSH terms

  • Animals
  • Calcification, Physiologic
  • Cell Differentiation
  • Collagen Type I
  • Discoidin Domain Receptor 2*
  • Enzyme Activation
  • Osteoblasts* / metabolism
  • Osteonectin* / genetics
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • Collagen Type I
  • Osteonectin
  • RNA, Small Interfering
  • Ddr2 protein, rat
  • Discoidin Domain Receptor 2
  • p38 Mitogen-Activated Protein Kinases