Inflammatory effects of TNFα are counteracted by X-ray irradiation and AChE inhibition in mouse micromass cultures

Chem Biol Interact. 2016 Nov 25;259(Pt B):313-318. doi: 10.1016/j.cbi.2016.03.027. Epub 2016 Mar 24.

Abstract

As a means to analyze anti-inflammatory effects by radiation and/or by cholinergic mechanisms, we found that cultured primary human osteoblasts express most cholinergic components. After X-ray irradiation, their level of acetylcholinesterase (AChE) was strongly elevated. As a 3D model, we cultured mesenchymal stem cells isolated from E11 mouse embryos as micromass nodules, and differentiated them into chondro- and osteoblasts. They were stimulated by 5 or 10 ng/ml of the inflammatory cytokine TNF-α to mimic an inflammatory condition in vitro, before exposure to 2 Gy X-rays. Effects on chondro- and osteoblasts of TNF-α, of X-rays, or both were analysed by Alcian Blue, or Alizarin Red staining, respectively. Acetylcholinesterase (AChE) activity was visualized histochemically. The results showed that treatment with TNF-α affected cartilage and bone formation in vitro, while X-rays reversed the effects of TNF-α. After irradiation, both AChE and alkaline phosphatase (ALP) activities, a marker for bone mineralization, were raised, suggesting that X-rays stimulated cholinergic mechanisms during calcification. Notably, the TNFα-effects on cultures were also counterbalanced after AChE activity was blocked by BW284c51. These findings suggest a complex crosstalk between radiation, cholinergic and inflammatory mechanisms, which could have wide significances, e.g. for understanding rheumatoid arthritis.

Keywords: Bone development; Cholinesterase inhibition; Inflammation; Mesenchymal stem cells; Micromass culture; X-rays irradiation.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / radiation effects
  • Cells, Cultured
  • Choline / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / radiation effects
  • Humans
  • Inflammation / pathology*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology
  • Osteoblasts / radiation effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • X-Rays

Substances

  • Cholinesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Acetylcholinesterase
  • Choline