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We aimed to explore a novel target, cathepsin K (Ctsk)\u2010mediated TLR9\u2010related autophagy, during the progress of periodontitis with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      DBA\/J1 mouse model of periodontitis with RA was created by local colonization of\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      (\n                      <jats:italic>Pg<\/jats:italic>\n                      ) and injection of collagen. The expression of Ctsk was inhibited by adeno\u2010associated virus (AAV). Micro\u2010CT, immunohistochemistry (IHC), Western blot and quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) were used to detect the expression of TLR9\u2010related autophagy in periodontitis with RA. Small interfering RNA (siRNA) and CpG oligodeoxynucleotides (CpG ODN) were applied in macrophages. Western blot, immunofluorescence (IF) and qRT\u2010PCR were used to verify the in vivo results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2010with\u2010RA 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\u2010related proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study advanced a novel role for Ctsk in TLR9 and autophagy to explain the interaction between periodontitis and RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.12722","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T05:42:27Z","timestamp":1574055747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Inhibition of Ctsk modulates periodontitis with arthritis via downregulation of TLR9 and autophagy"],"prefix":"10.1111","volume":"53","author":[{"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuwei","family":"Yin","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases Department of Prosthodontics West China Hospital of Stomatology Sichuan University Sichuan China"},{"name":"Stomatological Hospital Southern Medical University Guangzhou 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