Effects of mechanical stress on cytokine production in mandible-derived osteoblasts

Oral Dis. 2011 Oct;17(7):712-9. doi: 10.1111/j.1601-0825.2011.01832.x. Epub 2011 Jul 20.

Abstract

Objective: Mechanical stress is known to be an important factor in the regulation of bone remodeling, and mandibular bone is continuously exposed to mechanical stressors such as occlusal force. Therefore, in this study, we investigated the effects of mechanical stress approaching occlusal force, to which mandible-derived osteoblasts (MDOB) are exposed, on cytokine expression and production using an original hydrostatic pressure apparatus.

Materials and methods: The levels of cytokine in MDOB were examined by real-time RT-PCR, ELISA, and western blotting. In addition, mitogen-activated protein kinase inhibitor for ERK1/2, JNK, and p-38 pathways was used to identify the signal transduction pathway.

Results: Hydrostatic pressure increased the expression of IL-6 and TNF-α mRNA in a magnitude- and time-dependent manner and also enhanced IL-6 and TNF-α protein production. Furthermore, hydrostatic pressure changed the RANKL/OPG ratio in favor of RANKL for both mRNA and protein levels. Specific inhibitor of p-38 pathway but not that of the ERK1/2 and JNK pathways suppressed the up-regulation of RANKL production induced by hydrostatic pressure loading.

Conclusion: These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.

MeSH terms

  • Alkaline Phosphatase / analysis
  • Animals
  • Biomechanical Phenomena
  • Bite Force
  • Blotting, Western
  • Bone Remodeling / physiology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Hydrostatic Pressure
  • Interleukin-6 / biosynthesis
  • MAP Kinase Kinase 4 / antagonists & inhibitors
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mandible / cytology*
  • Mandible / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Osteoblasts / metabolism*
  • Osteoprotegerin / biosynthesis
  • RANK Ligand / biosynthesis
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Mechanical
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

  • Cytokines
  • Interleukin-6
  • Osteoprotegerin
  • RANK Ligand
  • Tnfrsf11b protein, mouse
  • Tumor Necrosis Factor-alpha
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Alkaline Phosphatase