Open AccessInhibition of Ctsk modulates periodontitis with arthritis via downregulation of TLR9 and autophagy
Author(s) -
Wei Wei,
Ren Jie,
Yin Wuwei,
Ding Handong,
Lu Qiuyu,
Tan Liangyu,
Deng Shibing,
Liu Jie,
Yang Qin,
Wang Jiajia,
Wang Min,
Yue Yuan,
Hao Liang
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12722
Subject(s) - autophagy , periodontitis , tlr9 , inflammation , porphyromonas gingivalis , western blot , biology , in vivo , immunology , medicine , apoptosis , gene expression , gene , biochemistry , microbiology and biotechnology , dna methylation
Objectives The mechanisms underlying the effects of Toll‐like receptor 9 (TLR9) and autophagy on rheumatoid arthritis (RA)‐aggravated periodontitis are unclear. We aimed to explore a novel target, cathepsin K (Ctsk)‐mediated TLR9‐related autophagy, during the progress of periodontitis with RA. Materials and Methods DBA/J1 mouse model of periodontitis with RA was created by local colonization of Porphyromonas gingivalis ( Pg ) and injection of collagen. The expression of Ctsk was inhibited by adeno‐associated virus (AAV). Micro‐CT, immunohistochemistry (IHC), Western blot and quantitative real‐time polymerase chain reaction (qRT‐PCR) were used to detect the expression of TLR9‐related autophagy in periodontitis with RA. Small interfering RNA (siRNA) and CpG oligodeoxynucleotides (CpG ODN) were applied in macrophages. Western blot, immunofluorescence (IF) and qRT‐PCR were used to verify the in vivo results. Results RA can promote periodontitis bone destruction in the lesion area, while inhibiting Ctsk could effectively alleviate this effect. The infiltration of macrophages, TLR9, autophagy proteins (TFEB and LC3) and inflammatory cytokines increased in the periodontitis‐with‐RA group and was reduced by the inhibition of Ctsk in the periodontal region. Macrophage stimulation confirmed the in vivo results. With the activation of TLR9 by CpG ODN, inhibition of Ctsk could suppress both TLR9 downstream signalling proteins and autophagy‐related proteins. Conclusions This study advanced a novel role for Ctsk in TLR9 and autophagy to explain the interaction between periodontitis and RA.