4-META對人類牙髓細胞的影響:自噬與焦亡作用的相關探討

Abstract

4-甲基丙烯酰氧基偏苯三酸酐 (4-methacryloxyethyl trimellitic anhydride, 4-META) 是一種常見的功能性單體 (functional monomer)，被廣泛使用在牙科樹脂黏著劑 (resin adhesive) 中。然而，這些樹脂材料可能因鍵結不穩定、聚合不完全，或於口腔環境中長時間水解等因素，於填充牙齒中或是接觸牙齒表面時，經由牙本質小管滲入牙髓中，進而對牙髓細胞造成潛在的傷害。我們過去的研究結果顯示，4-META 會使人類牙髓細胞中活性氧生成量增加，氧化壓力上升，細胞週期調控失序，細胞存活率降低以及促發炎因子生成。然 而，4-META 對牙髓細胞的毒性及其促發炎反應機制尚未被釐清，細胞因應的調節防護作用也有待瞭解。細胞自噬 (autophagy) 被認為是細胞面對外在毒性或壓力刺激時的重要自我防 禦與存活的機制之一;細胞焦亡(pyroptosis) 是一種具高度調控性的細胞死亡方式，與促發炎反應密切相關。近年來，這兩種機制在多種疾病模型中均展現出調控細胞命運與組織損傷 的重要角色。因此，本研究旨在於探討細胞自噬及細胞焦亡對於 4-META 誘導之人類牙髓 細胞毒性及促發炎反應扮演之角色，我們期望進一步釐清4-META 之細胞毒性的作用機 轉，並為未來開發生物相容性更高的牙科修復材料提供依據及潛在應用方向

4-Methacryloxyethyl trimellitic anhydride (4-META) is a widely used functional monomer in dental resin adhesives. However, these resin-based materials may release residual monomers due to unstable bonding, incomplete polymerization, or long-term hydrolysis under the moist environment of the oral cavity. These monomers can diffuse through dentinal tubules into the pulp tissue and potentially cause cytotoxic effects on dental pulp cells. Our previous studies have shown that 4- META increases intracellular reactive oxygen species (ROS), elevates oxidative stress, disrupts cell cycle regulation, decreases cell viability, and promotes the expression of pro-inflammatory cytokines in human dental pulp cells. However, the precise mechanisms underlying the cytotoxic and pro- inflammatory effects of 4-META remain unclear, and the potential cellular protective responses also warrant further investigation. Autophagy is regarded as an essential adaptive mechanism for cellular defense and survival under toxic or stress-inducing conditions. Pyroptosis, a highly regulated form of programmed cell death, is closely associated with inflammatory responses. In recent years, both autophagy and pyroptosis have been recognized as key regulators of cell fate and tissue injury in various disease models. Therefore, this study aims to investigate the roles of autophagy and pyroptosis in 4-META-induced cytotoxicity and inflammation in human dental pulp cells. We hope to elucidate the underlying mechanisms of 4-META toxicity and provide a scientific basis for developing dental restorative materials with improved biocompatibility.