{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:35:01Z","timestamp":1790696101199,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A5A2023879"],"award-info":[{"award-number":["NRF-2018R1A5A2023879"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cathepsin K (CTSK) is a cysteine protease that is mainly produced from mature osteoclasts and contributes to the destruction of connective tissues and mineralized matrix as a consequence of periodontal disease (PD). However, few studies have reported its regulatory role in osteoclastogenesis-supporting cells in inflammatory conditions. Here, we investigated the role of CTSK in osteoclastogenesis-supporting cells, focusing on the modulation of paracrine function. Microarray data showed that CTSK was upregulated in PD patients compared with healthy individuals, which was further supported by immunohistochemistry and qPCR analyses performed with human gingival tissues. The expression of CTSK in the osteoclastogenesis-supporting cells, including dental pulp stem cells, gingival fibroblasts, and periodontal ligament fibroblasts (PDLFs) was significantly elevated by treatment with inflammatory cytokines such as TNF\u03b1 and IL-1\u03b2. Moreover, TNF\u03b1 stimulation potentiated the PDLF-mediated osteoclastogenesis of bone marrow-derived macrophages. Interestingly, small interfering RNA-mediated silencing of CTSK in PDLF noticeably attenuated the TNF\u03b1-triggered upregulation of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor, and RANKL\/osteoprotegerin ratio, thereby abrogating the enhanced osteoclastogenesis-supporting activity of PDLF. Collectively, these results suggest a novel role of CTSK in the paracrine function of osteoclastogenesis-supporting cells in periodontal disease.<\/jats:p>","DOI":"10.3390\/ijms22020695","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T14:28:53Z","timestamp":1610461733000},"page":"695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Elevated Expression of Cathepsin K in Periodontal Ligament Fibroblast by Inflammatory Cytokines Accelerates Osteoclastogenesis via Paracrine Mechanism in Periodontal Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9361-732X","authenticated-orcid":false,"given":"Soon Chul","family":"Heo","sequence":"first","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Na","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YunJeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-8460","authenticated-orcid":false,"given":"Jae Joon","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Radiology and Dental Research Institute, Pusan National University, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Kyoung","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2962-9553","authenticated-orcid":false,"given":"Hyung Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1056\/NEJM199002083220606","article-title":"Periodontal disease","volume":"322","author":"Williams","year":"1990","journal-title":"N. 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