{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:24:59Z","timestamp":1793147099946,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP 15K11046"],"award-info":[{"award-number":["JP 15K11046"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Staphylococcus aureus is a main pathogen of osteomyelitis and protein A is a virulence factor with high affinity for IgG. In this study, we investigated whether S. aureus affects the differentiation and bone resorption of osteoclasts through the IgG-binding capacity of protein A. Staphylococcus aureus pre-treated with serum or IgG showed marked enhancement in osteoclastogenesis and bone resorption compared to non-treated S. aureus or a protein A-deficient mutant. Blocking of the Fc receptor and deletion of the Fc\u03b3 receptor gene in osteoclast precursor cells showed that enhanced osteoclastogenesis stimulated by S. aureus IgG immune complexes (ICs) was mediated by the Fc receptor on osteoclast precursor cells. In addition, osteoclastogenesis stimulated by S. aureus ICs but not the protein A-deficient mutant was markedly reduced in osteoclast precursor cells of Myd88-knockout mice. Moreover, NFATc1, Syk and NF-\u03baB signals were necessary for osteoclastogenesis stimulated by S. aureus ICs. The results suggest the contribution of a of Toll-like receptor 2 (TLR2)-Myd88 signal to the activity of S. aureus ICs. We further examined the expression of pro-inflammatory cytokines that is known to be enhanced by Fc\u03b3R-TLR cross-talk. Osteoclasts induced by S. aureus ICs showed higher expression of TNF-\u03b1 and IL-1\u03b2, and marked stimulation of proton secretion of osteoclasts activated by pro-inflammatory cytokines. Finally, injection of S. aureus, but not the protein A-deficient mutant, exacerbated bone loss in implantation and intra-peritoneal administration mouse models. Our results provide a novel mechanistic aspect of bone loss induced by S. aureus in which ICs and both Fc receptors and TLR pathways are involved.<\/jats:p>","DOI":"10.1093\/intimm\/dxz063","type":"journal-article","created":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T11:29:01Z","timestamp":1569497341000},"page":"89-104","source":"Crossref","is-referenced-by-count":26,"title":["IgG immune complexes with <i>Staphylococcus aureus<\/i> protein A enhance osteoclast differentiation and bone resorption by stimulating Fc receptors and TLR2"],"prefix":"10.1093","volume":"32","author":[{"given":"Asana","family":"Kamohara","sequence":"first","affiliation":[{"name":"Department of Pathology and Microbiology , Saga, Japan"},{"name":"Department of Oral & Maxillofacial Surgery , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology , Saga, Japan"},{"name":"Department of Orthopedic Surgery, Faculty of Medicine, Saga University , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghe","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology , Saga, Japan"},{"name":"Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dentistry, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology , Saga, Japan"},{"name":"Department of Orthopedic Surgery, Faculty of Medicine, Saga University , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakuo","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Department of Clinical Nutrition, Faculty of Health Science & Technology, Kawasaki University of Medical Welfare , Kurashiki, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine, Saga University , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kukita","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology & Oral Anatomy, Faculty of Dentistry, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Toyonaga","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuteru","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology & Molecular Imaging, Graduate School of Medicine , Hongo, Tokyo, Japan"},{"name":"Department of Chemistry & Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo , Hongo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Oral & Maxillofacial Surgery , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kukita","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology , Saga, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"2022070911583815800_CIT0001","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.chom.2013.05.015","article-title":"Staphylococcus aureus osteomyelitis: bad to the bone","volume":"13","author":"Olson","year":"2013","journal-title":"Cell Host Microbe"},{"key":"2022070911583815800_CIT0002","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fcimb.2015.00085","article-title":"Staphylococcus aureus vs. osteoblast: relationship and consequences in osteomyelitis","volume":"5","author":"Josse","year":"2015","journal-title":"Front. 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