TRAF-STOP alleviates osteoclastogenesis in periodontitis

作者：Huang, Yaxian; Wu, Jinyan; Zhan, Chi; Liu, Rong; Zhou, Zhaocai; Huang, Xin; Tian, Yaguang; Lin, Zhengmei^*; Song, Zhi^*

来源：Frontiers in Pharmacology, 2023, 14: 1119847.

DOI：10.3389/fphar.2023.1119847

• periodontitis
• osteoclast
• CD40L-CD40-TRAF6 axis
• TRAF-STOP
• NF-kappa B

The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-kappa B activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligationinduced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.

• 单位
  海南医学院; 中山大学