HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

J Orthop Surg Res. 2021 Jan 21;16(1):72. doi: 10.1186/s13018-021-02209-8.

Abstract

Background: Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells.

Methods: MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting.

Results: The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation.

Conclusions: Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

Keywords: HSP22; IL-6; Osteoblast; PGF2α; VEGF.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dinoprost / pharmacology*
  • Down-Regulation
  • Gene Knockdown Techniques
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / pharmacology
  • Heat-Shock Proteins / physiology*
  • Interleukin-6 / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Chaperones / genetics
  • Molecular Chaperones / pharmacology
  • Molecular Chaperones / physiology*
  • Osteoblasts / metabolism*
  • Phosphorylation
  • Vascular Endothelial Growth Factors / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Heat-Shock Proteins
  • Hspb8 protein, mouse
  • Interleukin-6
  • Molecular Chaperones
  • Vascular Endothelial Growth Factors
  • Dinoprost
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases