{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:38:14Z","timestamp":1772779094562,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periodontitis is one of the most common oral inflammatory diseases, and NOD-, LRR-, and pyrin domain-containing 3 (NLRP3)-mediated pyroptosis plays a crucial role in its pathogenesis. Cathepsin B (CTSB), a lysosomal cysteine protease, is closely associated with programmed cell death. Our study aimed to investigate the role of CTSB in periodontitis development through the NLRP3-mediated pyroptosis pathway and further explore the mechanism through which CTSB triggers NLRP3 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ligature-induced periodontitis were established in BALB\/c mice. Adeno-associated virus (AAV) was employed to downregulate CTSB expression in periodontal tissues. Small-interfering RNA (siRNA) was used to inhibit CTSB expression in macrophages for\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments. Micro-computed tomography (micro-CT) was employed to evaluate bone resorption. Immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to examine CTSB expression, pyroptosis proteins, and inflammatory factors. MitoSOX Red and DCFH-DA staining were applied to detect mitochondrial and intracellular reactive oxygen species (ROS) levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CTSB downregulation significantly reduced alveolar bone resorption and macrophage infiltration in periodontitis. Although NLRP3 and inflammatory cytokine levels increased in periodontitis, they were effectively reduced after CTSB inhibition in the periodontal region. Consistent with\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments, CTSB knockdown in macrophages also suppressed pyroptosis. Furthermore, both mitochondrial and intracellular ROS levels were decreased after CTSB inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibiting CTSB expression alleviates periodontitis, primarily by suppressing NLRP3-mediated pyroptosis in macrophages. The mechanism through which CTSB activates NLRP3 likely involves inducing mitochondrial ROS generation. These findings reveal a novel mechanistic axis (CTSB-mitochondrial ROS-NLRP3) in periodontitis, highlighting a potential conceptual target for future therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1762290","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:42Z","timestamp":1772775042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of Cathepsin B expression alleviates periodontitis by reducing mitochondrial reactive oxygen species production and NOD-, LRR-, and pyrin domain-containing 3 -mediated pyroptosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Tianqi","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay","place":["Kowloon, Hong Kong SAR, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral 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China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University","place":["Chengdu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for 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