Impact of PIEZO1-channel on inflammation and osteoclastogenesis mediated via periodontal ligament fibroblasts during mechanical loading.

The identification of mechanosensitive ion channels and their importance in innate immunity provides new starting points to elucidate the molecular mechanisms of orthodontic tooth movement. The mechanosensitive electron channel PIEZO1 (Piezo Type Mechanosensitive Ion Channel Component 1) may play a crucial role in orthodontic tooth movement. To investigate the role of the PIEZO1 channel, periodontal ligament fibroblasts (PDLF) were subsequently treated with a PIEZO1 inhibitor (GsMTx) with simultaneous pressure application or with an activator (JEDI2) without mechanical strain. The expression of genes and proteins involved in orthodontic tooth movement was examined by RT-qPCR, Western blot and ELISA. In addition, the effect on PDLF-mediated osteoclastogenesis was investigated in a coculture model using human monocytes. Inhibition of PIEZO1 under pressure application caused a reduction in RANKL (receptor activator of NF-kB ligand) expression, resulting in decreased osteoclastogenesis. On the other hand, activation of PIEZO1 without mechanical strain downregulated OPG (osteoprotegerin), resulting in increased osteoclastogenesis. PIEZO1 appears to play a role in the induction of inflammatory genes. It was also shown to influence osteoclastogenesis.

Dietary salt and myeloid NFAT5 (nuclear factor of activated T cells 5) impact on the number of bone-remodelling cells and frequency of root resorption during orthodontic tooth movement.

PURPOSE: The aim of the study was to investigate the impact of dietary salt and the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) in myeloid cells on bone remodelling cells as osteocytes, osteoblasts and osteoclasts and on force-induced dental root resorptions in a mouse model. METHODS: Control mice and mice lacking myeloid NFAT5 (nuclear factor of activated T cells 5) were either kept on low, normal or high salt diets. After one week on the specified diet an elastic band was inserted between the first and second molar to induce orthodontic tooth movement. One week later the mice were euthanised and jaws were fixed for histological analysis. Osteocyte, osteoblast and osteoclast numbers as well as extent of root resorptions were assessed histologically. RESULTS: Osteocyte number was diminished with high salt diet in wildtype mice. Osteoblast numbers increased with low salt diet in control mice and reduced with high salt diet in mice without NFAT5 in myeloid cells. High salt diet tended to increase osteoclast number in control mice. In mice without myeloid NFAT5, numbers of osteoclasts were reduced under high salt diet. Frequency of force-induced root resorptions tended to be dependent on dietary salt content in control mice. CONCLUSION: During orthodontic tooth movement dietary salt impacts on the frequency of root resorptions and the number of osteoclasts and osteoblasts in alveolar bone of mice. This can affect bone remodelling during orthodontic treatment. Myeloid NFAT5 impacts on this salt-dependent reaction.