生理的な咬合圧を受けた歯根膜から産生されるWnt5aによる三叉神経中脳路核細胞の分化機構の解明

抄録

Although many cohort studies have reported an association between poor oral function and the development of dementia, the detailed molecular physiological mechanisms linking them are still unclear. When occlusal pressure is applied to the teeth, primary sensations are transmitted from the Ruffini endings in the periodontal ligament (PDL) to the trigeminal ganglion (TG) and the trigeminal mesencephalic nucleus (Me5), and from the muscle spindles of the masseter muscle to the Me5. Primary sensory neurons are usually located outside the brain. However, the Me5 is exceptionally located inside the brainstem. Recently, we have reported that the rat PDL (rPDL) cells express NGF, BDNF, NT-4, and Wnt5a mRNA, but only Wnt5a mRNA in rPDL cells increases by mechanical stimulation. We hypothesize that factors released from mechanically stimulated PDL cells regulate the maintenance of the Me5 neurons. The rPDL cells, which we established from rat molar teeth, were loaded with periodic mechanical stimulation (0.5 Hz, 15% elongation). The culture medium for the primary mouse Me5 neurons was replaced with the supernatant media of the rPDL cells with or without mechanical stimulation. The supernatant medium of the mechanically stimulated rPDL cells enhanced the neurite outgrowth and this effect was suppressed by anti-Wnt5a antibody. In vivo, Wnt5a was significantly decreased in the Me5 after tooth extraction by ELISA. These results suggest that Wnt5a, produced by physiological mechanical stimulation on PDL, regulates the outgrowth of Me5 neurons.