Connexin43 reduces LPS-induced inflammation in hDPCs through TLR4-NF-κB pathway via hemichannels

Objectives: Connexin43 (Cx43) is involved in the inflammation of many tissue types. Dental caries is infectious disease resulting from mineralized tissue dissolution by a specific Bacterial population, causing pulp inflammation. However, Cx43's role in dental pulp remains unclear. Here, we investigated the function of Cx43 during pulp inflammation.

Materials and methods: We constructed a dentin injury model in Sprague-Dawley rats to investigate changes in Cx43 expression during pulp inflammation. Cx43 was inhibited in human dental pulp cells (hDPCs) that had been stimulated with lipopolysaccharide (LPS) to investigate the effect of Cx43 on inflammatory response. Promotion of TLR4-NF-κB pathway activity and special Cx43 channel inhibitors were used to clarify the function of Cx43 in hDPCs.

Results: Dentin injury led to low-level inflammation in dental pulp. Following dentin injury, Cx43 expression initially decreased before gradually recovering to normal levels. Cx43 inhibition reduced LPS-induced expression of inflammatory cytokines and NF-κB pathway activity. Promotion of NF-κB pathway activity counteracted the effect of Cx43 in hDPCs. Furthermore, inhibition of Cx43 hemichannels reduced LPS-induced inflammatory cytokine expression.

Conclusions: Cx43 is involved in inflammation of dental pulp, while its inhibition reduced LPS-induced inflammation in hDPCs through NF-κB pathway via blockage of hemichannels.

Connexin43; TLR4- NF-κB pathway; hemichannel; human dental pulp cells; inflammatory response.