Intercellular mitochondrial transfer alleviates pyroptosis in dental pulp damage

Abstract

Mitochondrial transfer is emerging as a promising therapeutic strategy for tissue repair, but whether it protects against pulpitis remains unclear. Here, we show that hyperactivated nucleotide‐binding domain and leucine‐rich repeat protein3 (NLRP3) inflammasomes with pyroptotic cell death was present in pulpitis tissues, especially in the odontoblast layer, and mitochondrial oxidative stress (OS) was involved in driving this NLRP3 inflammasome‐induced pathology. Using bone marrow mesenchymal stem cells (BMSCs) as mitochondrial donor cells, we demonstrated that BMSCs could donate their mitochondria to odontoblasts via tunnelling nanotubes (TNTs) and, thus, reduce mitochondrial OS and the consequent NLRP3 inflammasome‐induced pyroptosis in odontoblasts. These protective effects of BMSCs were mostly blocked by inhibitors of the mitochondrial function or TNT formation. In terms of the mechanism of action, TNF‐α secreted from pyroptotic odontoblasts activates NF‐κB signalling in BMSCs via the paracrine pathway, thereby promoting the TNT formation in BMSCs and enhancing mitochondrial transfer efficiency. Inhibitions of NF‐κB signalling and TNF‐α secretion in BMSCs suppressed their mitochondrial donation capacity and TNT formation. Collectively, these findings demonstrated that TNT‐mediated mitochondrial transfer is a potential protective mechanism of BMSCs under stress conditions, suggesting a new therapeutic strategy of mitochondrial transfer for dental pulp repair.

Mitochondrial Dysfunction in the Pathogenesis and Treatment of Oral Inflammatory Diseases

“…They confirmed that odontoblasts could receive exogenous mitochondria through tunneling nanotubes, thereby reducing mitochondrial dysfunction and ROS-NLRP3 inflammasome-triggered cell pyroptosis. When stress conditions occur, pyroptotic odontoblasts would increase TNF-αto-promoted tunneling nanotubes formation via NF-κB signaling, resulting in elevated mitochondrial transfer efficiency, which can be recognized as a self-defense mechanism [106]. To sum up, stabilizing mtDNA and developing effective measures to remove cytosolic mtDNA in time and transferring healthy mitochondria may be important for controlling inflammatory response and preventing irreversible pulp damage.…”