Dietary Salt Accelerates Orthodontic Tooth Movement by Increased Osteoclast Activity

Abstract

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.

Suppression of neutrophils by sodium exacerbates oxidative stress and arthritis

“…As our in vitro data showed an increased ROS production by neutrophils in high hypertonicity, we examined the effect of HSD in the STA arthritis model. In line with previous findings, our data show that HSD boosted osteoclast differentiation and bone erosion as seen in bone histology of osteoclast-specific TRAP staining ( 47 ). The aggravated arthritis in the STA mice on HSD was accompanied by high osteoclast count (N.Oc./B.Ar.…”

Impact of Myeloid p38α/MAPK on Orthodontic Tooth Movement

“…No influence of orthodontic tooth movement or deletion of p38α/MAPK on Opg gene expression was observed. This was in line with previous studies reporting that orthodontic treatment did not affect Opg expression in periodontal tissue [ 19 , 24 , 25 ]. Periodontal ligament fibroblasts react to mechanical strain in vitro with a reduction of Opg gene expression [ 27 ].…”

“…Macrophages were shown to react to mechanical stress with increased secretion of inflammatory factors like tumor necrosis factor, interleukin-6 (IL6), and prostaglandin E2 [ 6 ]. Here, no effects of orthodontic tooth movement on Tnf gene expression were detected, while Il6 and prostaglandin endoperoxide synthase 2 ( Ptgs2 ) were upregulated on the orthodontically treated maxillary jaw side, which was in line with several previous studies [ 19 , 24 , 25 ]. However, involvement of p38α/MAPK in this mechanically-induced upregulation has not been tested so far.…”

“…In in vitro experiments using osteoblasts, associations between p38 and OPG secretion were detected [ 29 ]. In contrast to Opg , Rankl gene expression was increased by orthodontic treatment in both wildtype [ 19 , 24 ] and p38α Δmyel mice. Gene expression of Rankl was increased, when p38α/MAPK was deleted in myeloid cells in periodontal tissue on both the control and orthodontically-treated maxillary jaw sides.…”

Sodium and its manifold impact on our immune system

“…On the one hand, HSD can stimulate certain components of the immune system, namely, to combat pathogens more efficiently [10,11,15] to fight cancer [12,13], or to elicit more vigorous autoimmune responses [6,16,17]. Moreover, HSD can boost osteoclast activity and thereby facilitate orthodontic tooth movement [18] and augment proinflammatory activation of microglia, which can aggravate stroke injury [19]. Of note, salt-losing tubulopathies (see Glossary) that result in sodium loss, have enhanced susceptibility to mucosal infections in humans [20].…”