{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:59:28Z","timestamp":1792515568899,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["22K05490"],"award-info":[{"award-number":["22K05490"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Toll-like receptors (TLRs) are pattern recognition receptors expressed in immune cells, including neutrophils, macrophages, and dendritic cells. Microbe-associated molecular patterns, including bacterial components, membranes, nucleic acids, and flagella are recognized by TLRs in inflammatory immune responses. Periodontal disease is an inflammatory disease known to cause local infections associated with gingival inflammation, subsequently leading to alveolar bone resorption. Prostaglandin E2 (PGE2) is a key mediator of TLR-induced inflammatory bone resorption. We previously reported that membrane-bound PGE synthase (mPGES-1)-deficient mice failed to induce bone resorption by lipopolysaccharide (LPS), a major pathogenic factor involved in periodontal bone resorption. Further experiments exploring specific pathogen-promoting osteoclast differentiation revealed that various TLR ligands induced osteoclast differentiation in a co-culture model. The ligands for TLR2\/1, TLR2\/6, TLR3, and TLR5, as well as TLR4, induce osteoclast differentiation associated with the production of PGE2 and the receptor activator of nuclear factor-kappa B ligand (RANKL), an inevitable inducer of osteoclast differentiation in osteoblasts. In vivo, local injection of TLR ligands, including TLR2\/1, TLR2\/6, and TLR3, resulted in severe alveolar bone resorption. This review summarizes the latest findings on TLR-mediated osteoclast differentiation and bone resorption in inflammatory diseases, such as periodontal diseases.<\/jats:p>","DOI":"10.3390\/biology13090692","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T04:28:28Z","timestamp":1725424108000},"page":"692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Roles of Toll-like Receptor Signaling in Inflammatory Bone Resorption"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-8951","authenticated-orcid":false,"given":"Tsukasa","family":"Tominari","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiho","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Cooperative Major of Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9103-7783","authenticated-orcid":false,"given":"Kensuke","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, 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Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan"},{"name":"Cooperative Major of Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan"},{"name":"Inada Research Unit, Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-shi, Tokyo 184-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Duan, T., Du, Y., Xing, C., Wang, H.Y., and Wang, R.F. 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