TRPV4 mediates macrophage polarization involved in inflammatory root resorption induced by mechanical pressure

In clinical orthodontic treatment, mechanical pressure applied to the tooth root triggers orthodontically induced inflammatory root resorption (OIIRR). An elevated M1/M2 macrophage polarization ratio is a key factor in OIIRR on the pressure side. However, the pathways through which macrophages perceive mechanical pressure stimuli remain unclear. The transient receptor potential vanilloid 4 channel, which is upregulated on the pressure side during orthodontic treatment, is a mechanically sensitive calcium ion channel protein that may play a crucial role in orthodontic periodontal mechanical signal transduction. Nevertheless, whether TRPV4 is involved in macrophage perception of and response to orthodontic force under mechanical pressure, thereby influencing macrophage polarization, requires further investigation. This study aims to explore the mechanism by which TRPV4 mediates mechanical pressure in regulating macrophage polarization, with the objective of providing new insights and strategies for mitigating OIIRR in clinical orthodontic practice. Studies have shown that resorption lacunae are present on the compressed root surface, with macrophages localized at the sites of root resorption. Mechanical pressure significantly upregulated intracellular Ca2+ concentration and macrophage expression levels of TRPV4, iNos, and CD86, while significantly downregulating the expression levels of Arg-1 and CD206. Treatment with the TRPV4 inhibitor GSK2193874 resulted in a significant downregulation of intracellular Ca2+ concentration and expression levels of iNos and CD86, and a significant upregulation of Arg-1 and CD206 expression levels. Therefore, our study demonstrates that TRPV4 senses mechanical pressure by promoting Ca2+ influx and upregulates the M1/M2 macrophage polarization ratio. In conclusion, our findings indicate that TRPV4 serves as a critical mediator in mechanical pressure-regulated macrophage polarization during OIIRR.