{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:08:32Z","timestamp":1791590912540,"version":"4.3.4"},"reference-count":172,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"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-2019R1A2C2007041"],"award-info":[{"award-number":["NRF-2019R1A2C2007041"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A5A2024418"],"award-info":[{"award-number":["NRF-2018R1A5A2024418"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1I1A1A01060952"],"award-info":[{"award-number":["NRF-2019R1I1A1A01060952"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gut microbiota has emerged as an important regulator of bone homeostasis. In particular, the modulation of innate immunity and bone homeostasis is mediated through the interaction between microbe-associated molecular patterns (MAMPs) and the host pattern recognition receptors including Toll-like receptors and nucleotide-binding oligomerization domains. Pathogenic bacteria such as Porphyromonas gingivalis and Staphylococcus aureus tend to induce bone destruction and cause various inflammatory bone diseases including periodontal diseases, osteomyelitis, and septic arthritis. On the other hand, probiotic bacteria such as Lactobacillus and Bifidobacterium species can prevent bone loss. In addition, bacterial metabolites and various secretory molecules such as short chain fatty acids and cyclic nucleotides can also affect bone homeostasis. This review focuses on the regulation of osteoclast and osteoblast by MAMPs including cell wall components and secretory microbial molecules under in vitro and in vivo conditions. MAMPs could be used as potential molecular targets for treating bone-related diseases such as osteoporosis and periodontal diseases.<\/jats:p>","DOI":"10.3390\/ijms22115805","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T11:33:20Z","timestamp":1622201600000},"page":"5805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Regulation of Bone Cell Differentiation and Activation by Microbe-Associated Molecular Patterns"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3923-1418","authenticated-orcid":false,"given":"Yeongkag","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaeyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jueun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-2887","authenticated-orcid":false,"given":"Cheol-Heui","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-3796","authenticated-orcid":false,"given":"Ok-Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-9278","authenticated-orcid":false,"given":"Seung Hyun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.clinbiochem.2012.03.021","article-title":"An overview of the regulation of bone remodelling at the cellular level","volume":"45","author":"Kular","year":"2012","journal-title":"Clin. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1146\/annurev.bioeng.8.061505.095721","article-title":"Biomechanical and molecular regulation of bone remodeling","volume":"8","author":"Robling","year":"2006","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-pathol-011110-130203","article-title":"Disorders of bone remodeling","volume":"6","author":"Feng","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Krauss, J.L., Roper, P.M., Ballard, A., Shih, C.C., Fitzpatrick, J.A.J., Cassat, J.E., Ng, P.Y., Pavlos, N.J., and Veis, D.J. (2019). Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly. mBio, 10.","DOI":"10.1128\/mBio.02447-19"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ijmm.2009.10.003","article-title":"Interaction of staphylococci with bone","volume":"300","author":"Wright","year":"2010","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1172\/JCI116106","article-title":"Lipopolysaccharide binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide. Implications for cytokine production in normal and injured lungs","volume":"90","author":"Martin","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11914-014-0195-2","article-title":"Bone and the innate immune system","volume":"12","author":"Charles","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6019","DOI":"10.1128\/IAI.71.10.6019-6026.2003","article-title":"Streptococcus pyogenes infection induces septic arthritis with increased production of the receptor activator of the NF-kappaB ligand","volume":"71","author":"Sakurai","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"22613","DOI":"10.18632\/oncotarget.4209","article-title":"Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model","volume":"6","author":"Fischman","year":"2015","journal-title":"Oncotarget"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"595962","DOI":"10.1155\/2014\/595962","article-title":"Effect of probiotics supplementation on bone mineral content and bone mass density","volume":"2014","author":"Parvaneh","year":"2014","journal-title":"Sci. World J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1172\/JCI86062","article-title":"Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics","volume":"126","author":"Li","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1002\/jcp.24340","article-title":"Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice","volume":"228","author":"McCabe","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41598-017-00623-9","article-title":"Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease","volume":"7","author":"Kobayashi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/jre.12164","article-title":"Topical treatment with probiotic Lactobacillus brevis CD2 inhibits experimental periodontal inflammation and bone loss","volume":"49","author":"Maekawa","year":"2014","journal-title":"J. Periodontal Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ni.2635","article-title":"Innate immune recognition of the microbiota promotes host-microbial symbiosis","volume":"14","author":"Chu","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1016\/0020-711X(93)90522-G","article-title":"Effects of short chain fatty acid, sodium butyrate, on osteoblastic cells and osteoclastic cells","volume":"25","author":"Iwami","year":"1993","journal-title":"Int. J. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/omi.12307","article-title":"Filifactor alocis-derived extracellular vesicles inhibit osteogenesis through TLR2 signaling","volume":"35","author":"Song","year":"2020","journal-title":"Mol. Oral Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1002\/jbmr.3701","article-title":"Cyclic Dinucleotides Inhibit Osteoclast Differentiation Through STING-Mediated Interferon-beta Signaling","volume":"34","author":"Kwon","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1146\/annurev.arplant.57.032905.105346","article-title":"A renaissance of elicitors: Perception of microbe-associated molecular patterns and danger signals by pattern-recognition receptors","volume":"60","author":"Boller","year":"2009","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Choi, H.W., and Klessig, D.F. (2016). DAMPs, MAMPs, and NAMPs in plant innate immunity. BMC Plant Biol., 16.","DOI":"10.1186\/s12870-016-0921-2"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00535-016-1242-9","article-title":"Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases","volume":"52","author":"Sun","year":"2017","journal-title":"J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-immunol-032414-112240","article-title":"Innate immune pattern recognition: A cell biological perspective","volume":"33","author":"Brubaker","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.smim.2006.12.004","article-title":"TLR signaling","volume":"19","author":"Kawai","year":"2007","journal-title":"Semin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.abb.2019.02.008","article-title":"NOD-like receptors and inflammasomes: A review of their canonical and non-canonical signaling pathways","volume":"670","author":"Platnich","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_26","unstructured":"Chatterjee, S., Jungraithmayr, W., and Bagchi, D. (2018). Immunity and Inflammation in Health and Disease: Emerging Roles of Nutraceuticals and Functional Foods in Immune Support, Academic Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00223-017-0331-y","article-title":"Gut Microbiota, Immune System, and Bone","volume":"102","author":"Sassi","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, M.F., Chang, C.H., Hu, C.C., Wu, Y.Y., Chang, Y., and Ueng, S.W.N. (2019). Periprosthetic Joint Infection Caused by Gram-Positive Versus Gram-Negative Bacteria: Lipopolysaccharide, but not Lipoteichoic Acid, Exerts Adverse Osteoclast-Mediated Effects on the Bone. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091289"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.14202\/vetworld.2018.161-166","article-title":"Effect of lipopolysaccharide derived from surabaya isolates of Actinobacillus actinomycetemcomitans on alveolar bone destruction","volume":"11","author":"Ridwan","year":"2018","journal-title":"Vet. World"},{"key":"ref_30","first-page":"229","article-title":"Membrane-associated interleukin-1 on macrophages stimulated with Actinobacillus actinomycetemcomitans lipopolysaccharide induces osteoclastic bone resorption in vivo","volume":"81","author":"Nishihara","year":"1995","journal-title":"Cytobios"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1359\/jbmr.2002.17.7.1211","article-title":"Dual modulation of osteoclast differentiation by lipopolysaccharide","volume":"17","author":"Zou","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12512","DOI":"10.1074\/jbc.M809789200","article-title":"Molecular mechanism of the bifunctional role of lipopolysaccharide in osteoclastogenesis","volume":"284","author":"Liu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1128\/IAI.67.6.2841-2846.1999","article-title":"Inhibition of osteoblastic cell differentiation by lipopolysaccharide extract from Porphyromonas gingivalis","volume":"67","author":"Kadono","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1359\/jbmr.090410","article-title":"LPS-induced inhibition of osteogenesis is TNF-alpha dependent in a murine tooth extraction model","volume":"24","author":"Tomomatsu","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.bbrc.2010.10.103","article-title":"Molecular mechanisms of the inhibitory effect of lipopolysaccharide (LPS) on osteoblast differentiation","volume":"402","author":"Bandow","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.joen.2016.01.012","article-title":"Lipoteichoic Acid of Enterococcus faecalis Inhibits the Differentiation of Macrophages into Osteoclasts","volume":"42","author":"Yang","year":"2016","journal-title":"J. Endod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/1753425918812646","article-title":"Lipoteichoic acid of Enterococcus faecalis inhibits osteoclastogenesis via transcription factor RBP-J","volume":"25","author":"Wang","year":"2019","journal-title":"Innate Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1189\/jlb.0309206","article-title":"Impaired osteoclastogenesis by staphylococcal lipoteichoic acid through Toll-like receptor 2 with partial involvement of MyD88","volume":"86","author":"Yang","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.bbrc.2017.02.062","article-title":"Staphylococcal lipoteichoic acid promotes osteogenic differentiation of mouse mesenchymal stem cells by increasing autophagic activity","volume":"485","author":"Liu","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hu, C.C., Chang, C.H., Hsiao, Y.M., Chang, Y., Wu, Y.Y., Ueng, S.W.N., and Chen, M.F. (2020). Lipoteichoic Acid Accelerates Bone Healing by Enhancing Osteoblast Differentiation and Inhibiting Osteoclast Activation in a Mouse Model of Femoral Defects. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155550"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/jbmr.1973","article-title":"Lipoproteins are an important bacterial component responsible for bone destruction through the induction of osteoclast differentiation and activation","volume":"28","author":"Kim","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1084\/jem.20040689","article-title":"MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha","volume":"200","author":"Sato","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e012","DOI":"10.1590\/1807-3107bor-2020.vol34.0012","article-title":"Pam2CSK4 (TLR2 agonist) induces periodontal destruction in mice","volume":"34","author":"Souza","year":"2020","journal-title":"Braz. Oral Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1292\/jvms.14-0463","article-title":"Porphyromonas gulae 41-kDa fimbriae induced osteoclast differentiation and cytokine production","volume":"77","author":"Sasaki","year":"2015","journal-title":"J. Vet. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0378-1097(03)00788-2","article-title":"Porphyromonas gingivalis 67-kDa fimbriae induced cytokine production and osteoclast differentiation utilizing TLR2","volume":"229","author":"Hiramine","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1128\/iai.62.7.3012-3016.1994","article-title":"Porphyromonas gingivalis fimbriae stimulate bone resorption in vitro","volume":"62","author":"Kawata","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1128\/iai.63.6.2374-2377.1995","article-title":"Porphyromonas gingivalis fimbria-stimulated bone resorption in vitro is inhibited by a tyrosine kinase inhibitor","volume":"63","author":"Hanazawa","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1902\/jop.2010.100501","article-title":"Fimbriae of Porphyromonas gingivalis are important for initial invasion of osteoblasts, but not for inhibition of their differentiation and mineralization","volume":"82","author":"Zhang","year":"2011","journal-title":"J. Periodontol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, W., Ju, J., Rigney, T., and Tribble, G. (2013). Integrin alpha5beta1-fimbriae binding and actin rearrangement are essential for Porphyromonas gingivalis invasion of osteoblasts and subsequent activation of the JNK pathway. BMC Microbiol., 13.","DOI":"10.1186\/1471-2180-13-5"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/j.1600-0765.2011.01452.x","article-title":"Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis","volume":"47","author":"Kishimoto","year":"2012","journal-title":"J. Periodontal Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"104990","DOI":"10.1016\/j.archoralbio.2020.104990","article-title":"Expression of osteoclastogenic and anti-osteoclastogenic cytokines differs in mouse gingiva injected with lipopolysaccharide, peptidoglycan, or both","volume":"122","author":"Ozaki","year":"2021","journal-title":"Arch. Oral Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"132765","DOI":"10.1155\/2015\/132765","article-title":"Muramyl dipeptide enhances lipopolysaccharide-induced osteoclast formation and bone resorption through increased RANKL expression in stromal cells","volume":"2015","author":"Ishida","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.archoralbio.2012.07.012","article-title":"Peptidoglycan of Actinomyces naeslundii induces inflammatory cytokine production and stimulates osteoclastogenesis in alveolar bone resorption","volume":"57","author":"Sato","year":"2012","journal-title":"Arch. Oral Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/imm.12654","article-title":"NOD1 in the modulation of host-microbe interactions and inflammatory bone resorption in the periodontal disease model","volume":"149","author":"Frasnelli","year":"2016","journal-title":"Immunology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8047610","DOI":"10.1155\/2018\/8047610","article-title":"Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity","volume":"2018","author":"Kitaura","year":"2018","journal-title":"Anal. Cell. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.chom.2013.04.005","article-title":"Induction of bone loss by pathobiont-mediated Nod1 signaling in the oral cavity","volume":"13","author":"Jiao","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1002\/jbmr.3137","article-title":"Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2","volume":"32","author":"Park","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1096\/fasebj.8.2.8119492","article-title":"Bacterial endotoxin: Molecular relationships of structure to activity and function","volume":"8","author":"Rietschel","year":"1994","journal-title":"FASEB J."},{"key":"ref_59","first-page":"383","article-title":"Structural analysis of lipopolysaccharides from Gram-negative bacteria","volume":"75","author":"Kabanov","year":"2010","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.1074\/jbc.274.16.10689","article-title":"Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction","volume":"274","author":"Chow","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1084\/jem.189.11.1777","article-title":"MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4","volume":"189","author":"Shimazu","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1053\/he.2000.5634","article-title":"Kupffer cell activation by lipopolysaccharide in rats: Role for lipopolysaccharide binding protein and toll-like receptor 4","volume":"31","author":"Su","year":"2000","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00018-014-1762-5","article-title":"Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling","volume":"72","author":"Plociennikowska","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/35092578","article-title":"Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction","volume":"413","author":"Fitzgerald","year":"2001","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7611","DOI":"10.1074\/jbc.274.12.7611","article-title":"Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes","volume":"274","author":"Zhang","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s43188-019-00030-4","article-title":"Beet root (Beta vulgaris) protects lipopolysaccharide and alcohol-induced liver damage in rat","volume":"36","author":"Kim","year":"2020","journal-title":"Toxicol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1128\/iai.62.2.390-397.1994","article-title":"Mouse interleukin-1 receptor antagonist induced by Actinobacillus actinomycetemcomitans lipopolysaccharide blocks the effects of interleukin-1 on bone resorption and osteoclast-like cell formation","volume":"62","author":"Nishihara","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.4049\/jimmunol.169.3.1516","article-title":"Stimulation by toll-like receptors inhibits osteoclast differentiation","volume":"169","author":"Takami","year":"2002","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.joen.2014.12.015","article-title":"Enterococcus faecalis attenuates the differentiation of macrophages into osteoclasts","volume":"41","author":"Park","year":"2015","journal-title":"J. Endod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.4049\/jimmunol.145.10.3297","article-title":"IL-6 is produced by osteoblasts and induces bone resorption","volume":"145","author":"Ishimi","year":"1990","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/jbmr.5650060807","article-title":"Evidence for interleukin-1 beta production by cultured normal human osteoblast-like cells","volume":"6","author":"Keeting","year":"1991","journal-title":"J. Bone Miner. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6819","DOI":"10.1128\/IAI.68.12.6819-6825.2000","article-title":"Impaired bone resorption by lipopolysaccharide in vivo in mice deficient in the prostaglandin E receptor EP4 subtype","volume":"68","author":"Sakuma","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.4049\/jimmunol.166.5.3574","article-title":"Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via Toll-like receptors","volume":"166","author":"Kikuchi","year":"2001","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev-micro-091213-112949","article-title":"Lipoteichoic acid synthesis and function in gram-positive bacteria","volume":"68","author":"Percy","year":"2014","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1007\/s12272-016-0804-y","article-title":"Lipoteichoic acids as a major virulence factor causing inflammatory responses via Toll-like receptor 2","volume":"39","author":"Kang","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.neuroscience.2004.09.067","article-title":"Signal transduction pathways of nitric oxide release in primary microglial culture challenged with gram-positive bacterial constituent, lipoteichoic acid","volume":"133","author":"Chien","year":"2005","journal-title":"Neuroscience"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1016\/j.molimm.2011.07.009","article-title":"Lipoteichoic acid from Lactobacillus plantarum induces nitric oxide production in the presence of interferon-gamma in murine macrophages","volume":"48","author":"Kang","year":"2011","journal-title":"Mol. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.molimm.2013.10.004","article-title":"Lipoteichoic acid of Streptococcus mutans interacts with Toll-like receptor 2 through the lipid moiety for induction of inflammatory mediators in murine macrophages","volume":"57","author":"Hong","year":"2014","journal-title":"Mol. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.4049\/jimmunol.177.5.3162","article-title":"Not lipoteichoic acid but lipoproteins appear to be the dominant immunobiologically active compounds in Staphylococcus aureus","volume":"177","author":"Hashimoto","year":"2006","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1038\/s41467-017-02234-4","article-title":"Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses","volume":"8","author":"Nguyen","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0952-7915(02)00013-4","article-title":"Mammalian Toll-like receptors","volume":"15","author":"Akira","year":"2003","journal-title":"Curr. Opin. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8406","DOI":"10.1074\/jbc.M809618200","article-title":"The Triacylated ATP Binding Cluster Transporter Substrate-binding Lipoprotein of Staphylococcus aureus Functions as a Native Ligand for Toll-like Receptor 2","volume":"284","author":"Kurokawa","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.cell.2007.09.008","article-title":"Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide","volume":"130","author":"Jin","year":"2007","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.immuni.2009.09.018","article-title":"Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer","volume":"31","author":"Kang","year":"2009","journal-title":"Immunity"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"24192","DOI":"10.1074\/jbc.M109.023044","article-title":"MyD88 adapter-like (Mal)\/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses","volume":"284","author":"Verstak","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"126392","DOI":"10.1016\/j.micres.2019.126392","article-title":"The cell surface adhesins of Mycobacterium tuberculosis","volume":"232","author":"Vinod","year":"2020","journal-title":"Microbiol. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ijbiomac.2018.01.151","article-title":"Host-bacteria interaction and adhesin study for development of therapeutics","volume":"112","author":"Solanki","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.cell.2006.02.012","article-title":"Bacterial adhesion and entry into host cells","volume":"124","author":"Cossart","year":"2006","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-6976.2007.00094.x","article-title":"Peptidoglycan structure and architecture","volume":"32","author":"Vollmer","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1073\/pnas.0507656103","article-title":"Dual strategies for peptidoglycan discrimination by peptidoglycan recognition proteins (PGRPs)","volume":"103","author":"Swaminathan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3892\/ijmm.2012.878","article-title":"NOD1 and NOD2 stimulation triggers innate immune responses of human periodontal ligament cells","volume":"29","author":"Jeon","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"27823","DOI":"10.1074\/jbc.M003415200","article-title":"An induced proximity model for NF-kappa B activation in the Nod1\/RICK and RIP signaling pathways","volume":"275","author":"Inohara","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/embo-reports\/kve155","article-title":"CARD4\/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri","volume":"2","author":"Girardin","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1177\/0022034515606045","article-title":"Oral Microbiome Metabolism: From \u201cWho Are They?\u201d to \u201cWhat Are They Doing?\u201d","volume":"94","author":"Takahashi","year":"2015","journal-title":"J. Dent. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1136\/gut.22.9.763","article-title":"Short chain fatty acids in the human colon","volume":"22","author":"Cummings","year":"1981","journal-title":"Gut"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1152\/physrev.1990.70.2.567","article-title":"Energy contributions of volatile fatty acids from the gastrointestinal tract in various species","volume":"70","author":"Bergman","year":"1990","journal-title":"Physiol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41580-018-0049-3","article-title":"Mechanisms of signalling and biased agonism in G protein-coupled receptors","volume":"19","author":"Wootten","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/cphy.c170050","article-title":"Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology","volume":"8","author":"Priyadarshini","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"32913","DOI":"10.1074\/jbc.M805601200","article-title":"Conserved polar residues in transmembrane domains V, VI, and VII of free fatty acid receptor 2 and free fatty acid receptor 3 are required for the binding and function of short chain fatty acids","volume":"283","author":"Stoddart","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5092","DOI":"10.1210\/en.2005-0545","article-title":"Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43","volume":"146","author":"Hong","year":"2005","journal-title":"Endocrinology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.intimp.2013.06.034","article-title":"Neutrophil cell surface receptors and their intracellular signal transduction pathways","volume":"17","author":"Futosi","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.3389\/fimmu.2019.02031","article-title":"Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41413-019-0059-6","article-title":"The role of GPCRs in bone diseases and dysfunctions","volume":"7","author":"Luo","year":"2019","journal-title":"Bone Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Yi, S.J., Lee, H., Lee, J., Lee, K., Kim, J., Kim, Y., Park, J.I., and Kim, K. (2019). Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133147"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.4110\/in.2019.19.e9","article-title":"Short-chain Fatty Acids Inhibit Staphylococcal Lipoprotein-induced Nitric Oxide Production in Murine Macrophages","volume":"19","author":"Park","year":"2019","journal-title":"Immune Netw."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fimmu.2018.00055","article-title":"Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate","volume":"9","author":"Sim","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1080\/19490976.2017.1371893","article-title":"Mechanisms of gut microbiota-mediated bone remodeling","volume":"9","author":"Yan","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1182\/blood-2002-08-2622","article-title":"Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages","volume":"101","author":"Rahman","year":"2003","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Chang, M.C., Chen, Y.J., Lian, Y.C., Chang, B.E., Huang, C.C., Huang, W.L., Pan, Y.H., and Jeng, J.H. (2018). Butyrate Stimulates Histone H3 Acetylation, 8-Isoprostane Production, RANKL Expression, and Regulated Osteoprotegerin Expression\/Secretion in MG-63 Osteoblastic Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124071"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6542","DOI":"10.1074\/jbc.M112.429084","article-title":"The free fatty acid receptor G protein-coupled receptor 40 (GPR40) protects from bone loss through inhibition of osteoclast differentiation","volume":"288","author":"Wauquier","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.bone.2019.05.016","article-title":"Short-chain fatty acids and FFAR2 as suppressors of bone resorption","volume":"125","author":"Duffles","year":"2019","journal-title":"Bone"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2334\/josnusd.53.509","article-title":"High concentration of sodium butyrate suppresses osteoblastic differentiation and mineralized nodule formation in ROS17\/2.8 cells","volume":"53","author":"Morozumi","year":"2011","journal-title":"J. Oral Sci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Chang, M.C., Tsai, Y.L., Liou, E.J., Tang, C.M., Wang, T.M., Liu, H.C., Liao, M.W., Yeung, S.Y., Chan, C.P., and Jeng, J.H. (2016). Effect of Butyrate on Collagen Expression, Cell Viability, Cell Cycle Progression and Related Proteins Expression of MG-63 Osteoblastic Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165438"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41467-017-02490-4","article-title":"Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss","volume":"9","author":"Lucas","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Kalluri, R., and LeBleu, V.S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367.","DOI":"10.1126\/science.aau6977"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41579-018-0112-2","article-title":"Types and origins of bacterial membrane vesicles","volume":"17","author":"Toyofuku","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1002\/pmic.200700196","article-title":"Global proteomic profiling of native outer membrane vesicles derived from Escherichia coli","volume":"7","author":"Lee","year":"2007","journal-title":"Proteomics"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4248","DOI":"10.1128\/AEM.71.8.4248-4253.2005","article-title":"Naturally occurring DNA transfer system associated with membrane vesicles in cellulolytic Ruminococcus spp. of ruminal origin","volume":"71","author":"Klieve","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Macia, L., Nanan, R., Hosseini-Beheshti, E., and Grau, G.E. (2019). Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010107"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Codemo, M., Muschiol, S., Iovino, F., Nannapaneni, P., Plant, L., Wai, S.N., and Henriques-Normark, B. (2018). Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses. mBio, 9.","DOI":"10.1128\/mBio.00559-18"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"43","DOI":"10.11613\/BM.2013.007","article-title":"Osteoimmunology and the influence of pro-inflammatory cytokines on osteoclasts","volume":"23","author":"Zupan","year":"2013","journal-title":"Biochem. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3389\/fmicb.2015.00496","article-title":"Bacterial exopolysaccharides: Biosynthesis pathways and engineering strategies","volume":"6","author":"Schmid","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"14002","DOI":"10.3390\/ijms131114002","article-title":"Bacterial exopolysaccharides: Functionality and prospects","volume":"13","author":"Nwodo","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000081689","article-title":"Capsular polysaccharides and their role in virulence","volume":"12","author":"Taylor","year":"2005","journal-title":"Contrib. Microbiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jobm.200610203","article-title":"Bacterial exopolysaccharides\u2014A perception","volume":"47","author":"Kumar","year":"2007","journal-title":"J. Basic Microbiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s00223-020-00790-4","article-title":"An Exopolysaccharide Produced by Bifidobacterium longum 35624(R) Inhibits Osteoclast Formation via a TLR2-Dependent Mechanism","volume":"108","author":"Wallimann","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s00223-001-2091-x","article-title":"A new bone-healing material: A hyaluronic acid-like bacterial exopolysaccharide","volume":"72","author":"Zanchetta","year":"2003","journal-title":"Calcif. Tissue Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/glycob\/cwr002","article-title":"Effects of a sulfated exopolysaccharide produced by Altermonas infernus on bone biology","volume":"21","author":"Velasco","year":"2011","journal-title":"Glycobiology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1128\/iai.63.5.1893-1898.1995","article-title":"Actinobacillus actinomycetemcomitans Y4 capsular-polysaccharide-like polysaccharide promotes osteoclast-like cell formation by interleukin-1 alpha production in mouse marrow cultures","volume":"63","author":"Nishihara","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1399-302X.1995.tb00121.x","article-title":"Role of prostaglandin in the formation of osteoclasts induced by capsular-like polysaccharide antigen of Actinobacillus actinomycetemcomitans strain Y4","volume":"10","author":"Ueda","year":"1995","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1177\/00220345990780060601","article-title":"Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells","volume":"78","author":"Yamamoto","year":"1999","journal-title":"J. Dent. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1128\/IAI.71.4.2283-2287.2003","article-title":"Immunization with Porphyromonas gingivalis capsular polysaccharide prevents P. gingivalis-elicited oral bone loss in a murine model","volume":"71","author":"Gonzalez","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/325279a0","article-title":"Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid","volume":"325","author":"Ross","year":"1987","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.cell.2013.08.014","article-title":"Cyclic dinucleotides and the innate immune response","volume":"154","author":"Danilchanka","year":"2013","journal-title":"Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrmicro3069","article-title":"Cyclic di-AMP: Another second messenger enters the fray","volume":"11","author":"Corrigan","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1574-6968.2006.00493.x","article-title":"Proteins with GGDEF and EAL domains regulate Pseudomonas putida biofilm formation and dispersal","volume":"265","author":"Gjermansen","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1128\/IAI.00447-16","article-title":"Cyclic di-AMP Released from Staphylococcus aureus Biofilm Induces a Macrophage Type I Interferon Response","volume":"84","author":"Gries","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature07317","article-title":"STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling","volume":"455","author":"Ishikawa","year":"2008","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e00018-13","DOI":"10.1128\/mBio.00018-13","article-title":"STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection","volume":"4","author":"Barker","year":"2013","journal-title":"mBio"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/s41586-019-1000-2","article-title":"Structural basis of STING binding with and phosphorylation by TBK1","volume":"567","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"ra20","DOI":"10.1126\/scisignal.2002521","article-title":"STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway","volume":"5","author":"Tanaka","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.febslet.2015.02.018","article-title":"Transmembrane protein 173 inhibits RANKL-induced osteoclast differentiation","volume":"589","author":"Choe","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/art.39863","article-title":"STING Contributes to Abnormal Bone Formation Induced by Deficiency of DNase II in Mice","volume":"69","author":"Baum","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/416744a","article-title":"RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta","volume":"416","author":"Takayanagi","year":"2002","journal-title":"Nature"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.molcel.2018.07.034","article-title":"Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-kappaB Signaling after Nuclear DNA Damage","volume":"71","author":"Dunphy","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"ofz181","DOI":"10.1093\/ofid\/ofz181","article-title":"The History of Antibiotic Treatment of Osteomyelitis","volume":"6","author":"Kulkarni","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jtbi.2008.10.025","article-title":"Exploring the role of the immune response in preventing antibiotic resistance","volume":"256","author":"Handel","year":"2009","journal-title":"J. Theor. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: Mechanism of action and role in clinical practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/ijcp.12022","article-title":"Denosumab: Mechanism of action and clinical outcomes","volume":"66","author":"Hanley","year":"2012","journal-title":"Int. J. Clin. Pract."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3892\/or.2016.4986","article-title":"Parathyroid hormone\/parathyroid hormone-related peptide regulate osteosarcoma cell functions: Focus on the extracellular matrix (Review)","volume":"36","author":"Nikitovic","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00198-010-1177-6","article-title":"Denosumab-related osteonecrosis of the jaws","volume":"22","author":"Kyrgidis","year":"2011","journal-title":"Osteoporos. Int."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1053\/berh.2001.0161","article-title":"Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis","volume":"15","author":"Woo","year":"2001","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Park, O.J., Kwon, Y., Park, C., So, Y.J., Park, T.H., Jeong, S., Im, J., Yun, C.H., and Han, S.H. (2020). Streptococcus gordonii: Pathogenesis and Host Response to Its Cell Wall Components. Microorganisms, 8.","DOI":"10.3390\/microorganisms8121852"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12016-015-8522-7","article-title":"Animal Models of Bone Loss in Inflammatory Arthritis: From Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review","volume":"51","author":"Alves","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1002\/art.24781","article-title":"Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo","volume":"60","author":"Axmann","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3389\/fphys.2017.00508","article-title":"Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics","volume":"8","author":"Gao","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.3389\/fimmu.2019.01663","article-title":"Finding a Toll on the Route: The Fate of Osteoclast Progenitors After Toll-Like Receptor Activation","volume":"10","author":"Souza","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Jung, K., Lee, J.E., Kim, H.Z., Kim, H.M., Park, B.S., Hwang, S.I., Lee, J.O., Kim, S.C., and Koh, G.Y. (2009). Toll-like receptor 4 decoy, TOY, attenuates gram-negative bacterial sepsis. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007403"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Andresen, L., Theodorou, K., Grunewald, S., Czech-Zechmeister, B., Konnecke, B., Luhder, F., and Trendelenburg, G. (2016). Evaluation of the Therapeutic Potential of Anti-TLR4-Antibody MTS510 in Experimental Stroke and Significance of Different Routes of Application. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148428"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.3389\/fimmu.2018.01704","article-title":"Inhibition of Lipopolysaccharide- and Lipoprotein-Induced Inflammation by Antitoxin Peptide Pep19-2.5","volume":"9","author":"Heinbockel","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/jsre.2001.6227","article-title":"Lipopolysaccharide: Neutralization by polymyxin B shuts down the signaling pathway of nuclear factor kappaB in peripheral blood mononuclear cells, even during activation","volume":"100","author":"Tsuzuki","year":"2001","journal-title":"J. Surg. Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/jbmr.3635","article-title":"Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption","volume":"34","author":"Schepper","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1002\/jcp.24636","article-title":"Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model","volume":"229","author":"Britton","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1210\/EN.2015-1308","article-title":"Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri","volume":"156","author":"Zhang","year":"2015","journal-title":"Endocrinology"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/jcpe.12838","article-title":"Probiotic Lactobacillus rhamnosus GG prevents alveolar bone loss in a mouse model of experimental periodontitis","volume":"45","author":"Gatej","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.1021\/jf2013716","article-title":"Antiosteoporotic effects of Lactobacillus-fermented soy skim milk on bone mineral density and the microstructure of femoral bone in ovariectomized mice","volume":"59","author":"Chiang","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"5387","DOI":"10.2147\/IJN.S130485","article-title":"Probiotics protect mice from CoCrMo particles-induced osteolysis","volume":"12","author":"Wang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1177271919843825","DOI":"10.1177\/1177271919843825","article-title":"Circulatory Levels of RANKL, OPG, and Oxidative Stress Markers in Postmenopausal Women With Normal or Low Bone Mineral Density","volume":"14","author":"Azizieh","year":"2019","journal-title":"Biomark. Insights"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1172\/JCI128521","article-title":"The gut-bone axis: How bacterial metabolites bridge the distance","volume":"129","author":"Zaiss","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1083\/jcb.200201089","article-title":"Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor","volume":"157","author":"Kato","year":"2002","journal-title":"J. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:04Z","timestamp":1760163004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/5805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":172,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22115805"],"URL":"https:\/\/doi.org\/10.3390\/ijms22115805","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,28]]}}}