Sasagawa Karin, Domon Hisanori, Hirayama Satoru, Maekawa Tomoki, Isono Toshihito, Tabeta Koichi, Terao Yutaka
Division of Microbiology and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Commun Biol. 2025 May 16;8(1):760. doi: 10.1038/s42003-025-08197-3.
Periodontitis is characterized by the activity of neutrophil elastase, a host defense factor that leads to the destruction of the epithelial barrier and bacterial invasion of the periodontal tissue. Secretory leukocyte protease inhibitors (SLPI), predominantly secreted by epithelial cells, diffuse into the mucosal surface and inhibit excessive tissue loss caused by elastase during inflammation. The SLPI level is high in healthy gingiva and low in severe periodontitis. In this study, we hypothesized that intragingival administration of SLPI inhibits periodontal tissue destruction caused by periodontitis. Administration of SLPI significantly reduced neutrophil elastase activity in periodontal tissue and alleviated alveolar bone loss in mice. Real-time PCR analysis revealed that SLPI administration downregulated the transcription of pro-inflammatory cytokines and osteoclast-related factors in the gingival tissue. Furthermore, in vitro treatment of bone marrow macrophages with SLPI resulted in the downregulation of osteoclast differentiation. SLPI treatment of MC3T3-E1 cells promoted osteoblast differentiation and bone formation. These findings suggest that SLPI protects against periodontal tissue damage by suppressing inflammation and bone resorption and promoting bone regeneration.
牙周炎的特征是中性粒细胞弹性蛋白酶的活性，这是一种宿主防御因子，可导致上皮屏障破坏和细菌侵入牙周组织。分泌型白细胞蛋白酶抑制剂（SLPI）主要由上皮细胞分泌，扩散到粘膜表面，并在炎症期间抑制弹性蛋白酶引起的过度组织损伤。SLPI水平在健康牙龈中较高，在严重牙周炎中较低。在本研究中，我们假设龈内给予SLPI可抑制牙周炎引起的牙周组织破坏。给予SLPI可显著降低牙周组织中的中性粒细胞弹性蛋白酶活性，并减轻小鼠的牙槽骨丢失。实时PCR分析显示，给予SLPI可下调牙龈组织中促炎细胞因子和破骨细胞相关因子的转录。此外，用SLPI体外处理骨髓巨噬细胞导致破骨细胞分化下调。用SLPI处理MC3T3-E1细胞可促进成骨细胞分化和骨形成。这些发现表明，SLPI通过抑制炎症和骨吸收以及促进骨再生来预防牙周组织损伤。
