{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:35:56Z","timestamp":1791462956655,"version":"4.3.4"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Adelaide University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Osteoporos Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose of the Review<\/jats:title>\n                    <jats:p>The osteoblast lineage has traditionally been viewed through a structural and metabolic lens, yet growing evidence indicates that these cells possess diverse functions, including roles in innate and adaptive immune responses. To establish a coherent mechanistic framework, we performed a systematic review of the literature concerning immune signalling, antigen presentation, and pathogen responses across the osteoblast lineage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>We identified 463 unique studies, with 43 meeting the inclusion criteria. Our synthesis reveals a stage-specialised immune continuum. Osteoprogenitors appear to initiate early inflammatory signalling while mature osteoblasts operate as microbial sensors and conditional antigen-presenting cells via inducible expression of cell membrane and cytosolic pattern recognition receptors, and a functional major histocompatibility complex class II apparatus. Osteocytes, the most abundant and long-lived bone cell type, are also capable of detecting microbial danger and activate extensive interferon, chemokine and cytokine programmes within the lacunocanalicular network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Together, these properties define a stromal immune system that coordinates both innate and adaptive immunity across bone surfaces and the mineralised matrix. This osteoblast lineage-integrated immune architecture provides a conceptual basis for understanding osteomyelitis incidence and persistence, biomaterial\u2013immune interactions, as well as inflammatory bone remodelling, reframing this lineage as a previously underappreciated regulator of skeletal and systemic immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11914-026-00970-5","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:17:45Z","timestamp":1778563065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Innate and Adaptive Immune Functions of Osteoblast-Lineage Cells"],"prefix":"10.1007","volume":"24","author":[{"given":"Mohammad A.","family":"Hossain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Plinio R.","family":"Hurtado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Atkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"970_CR1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1196\/annals.1402.018","volume":"1116","author":"LF Bonewald","year":"2007","unstructured":"Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann Ny Acad Sci. 2007;1116:281\u201390. https:\/\/doi.org\/10.1196\/annals.1402.018.","journal-title":"Ann Ny Acad Sci"},{"issue":"1","key":"970_CR2","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1152\/physrev.00043.2020","volume":"102","author":"J Delgado-Calle","year":"2022","unstructured":"Delgado-Calle J, Bellido T. The osteocyte as a signaling cell. Physiol Rev. 2022;102(1):379\u2013410. https:\/\/doi.org\/10.1152\/physrev.00043.2020.","journal-title":"Physiol Rev"},{"issue":"2","key":"970_CR3","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.bone.2012.10.013","volume":"54","author":"J Klein-Nulend","year":"2013","unstructured":"Klein-Nulend J, Bakker AD, Bacabac RG, Vatsa A, Weinbaum S. Mechanosensation and transduction in osteocytes. Bone. 2013;54(2):182\u201390. https:\/\/doi.org\/10.1016\/j.bone.2012.10.013.","journal-title":"Bone"},{"key":"970_CR4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.coph.2016.02.003","volume":"28","author":"M Prideaux","year":"2016","unstructured":"Prideaux M, Findlay DM, Atkins GJ, Osteocytes. The master cells in bone remodelling. Curr Opin Pharmacol. 2016;28:24\u201330. https:\/\/doi.org\/10.1016\/j.coph.2016.02.003.","journal-title":"Curr Opin Pharmacol"},{"issue":"10","key":"970_CR5","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/s41577-019-0178-8","volume":"19","author":"M Tsukasaki","year":"2019","unstructured":"Tsukasaki M, Takayanagi H. Osteoimmunology: evolving concepts in bone-immune interactions in health and disease. Nat Rev Immunol. 2019;19(10):626\u201342. https:\/\/doi.org\/10.1038\/s41577-019-0178-8.","journal-title":"Nat Rev Immunol"},{"key":"970_CR6","doi-asserted-by":"publisher","first-page":"7813","DOI":"10.2147\/IJGM.S558927","volume":"18","author":"L Chen","year":"2025","unstructured":"Chen L, Liang L. Osteoimmunology of Osteoporosis in Rheumatoid Arthritis: Emerging Mechanisms and Therapeutic Implications. Int J Gen Med. 2025;18:7813\u201322. https:\/\/doi.org\/10.2147\/IJGM.S558927.","journal-title":"Int J Gen Med"},{"key":"970_CR7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.bone.2018.02.012","volume":"119","author":"P Divieti Pajevic","year":"2019","unstructured":"Divieti Pajevic P, Krause DS. Osteocyte regulation of bone and blood. Bone. 2019;119:13\u20138. https:\/\/doi.org\/10.1016\/j.bone.2018.02.012.","journal-title":"Bone"},{"key":"970_CR8","doi-asserted-by":"publisher","first-page":"116296","DOI":"10.1016\/j.bone.2021.116296","volume":"168","author":"D Grcevic","year":"2023","unstructured":"Grcevic D, Sanjay A, Lorenzo J. Interactions of B-lymphocytes and bone cells in health and disease. Bone. 2023;168:116296. https:\/\/doi.org\/10.1016\/j.bone.2021.116296.","journal-title":"Bone"},{"issue":"1","key":"970_CR9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-023-00249-w","volume":"11","author":"H Zhang","year":"2023","unstructured":"Zhang H, Liesveld JL, Calvi LM, Lipe BC, Xing L, Becker MW, et al. The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies. Bone Res. 2023;11(1):15. https:\/\/doi.org\/10.1038\/s41413-023-00249-w.","journal-title":"Bone Res"},{"key":"970_CR10","doi-asserted-by":"publisher","unstructured":"Yang D, Wijenayaka AR, Solomon LB, Pederson SM, Findlay DM, Kidd SP, Atkins GJ. Novel Insights into Staphylococcus aureus Deep Bone Infections: the Involvement of Osteocytes. Mbio. 2018;9(2). https:\/\/doi.org\/10.1128\/mBio.00415-18.","DOI":"10.1128\/mBio.00415-18"},{"issue":"6","key":"970_CR11","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1007\/s00774-006-0708-x","volume":"24","author":"K Maruyama","year":"2006","unstructured":"Maruyama K, Sano G, Matsuo K. Murine osteoblasts respond to LPS and IFN-gamma similarly to macrophages. J Bone Min Metab. 2006;24(6):454\u201360. https:\/\/doi.org\/10.1007\/s00774-006-0708-x.","journal-title":"J Bone Min Metab"},{"issue":"5","key":"970_CR12","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/s8756-3282(03)00265-5","volume":"33","author":"LW Schrum","year":"2003","unstructured":"Schrum LW, Bost KL, Hudson MC, Marriott I. Bacterial infection induces expression of functional MHC class II molecules in murine and human osteoblasts. Bone. 2003;33(5):812\u201321. https:\/\/doi.org\/10.1016\/s8756-3282(03)00265-5.","journal-title":"Bone"},{"issue":"1","key":"970_CR13","doi-asserted-by":"publisher","first-page":"e70130","DOI":"10.1002\/jor.70130","volume":"44","author":"G Muthukrishnan","year":"2026","unstructured":"Muthukrishnan G, Coraca-Huber DC, Atkins GJ, Abbaszadeh A, Abedi AA, Abuhussein E, et al. 2025 International Consensus Meeting on Musculoskeletal Infection: Summary From the Biofilm Workgroup on Biofilm Formation, Persistence, and Host-Environment Interactions. J Orthop Res. 2026;44(1):e70130. https:\/\/doi.org\/10.1002\/jor.70130.","journal-title":"J Orthop Res"},{"issue":"12","key":"970_CR14","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1302\/0301-620X.105B12.BJJ-2023-0454.R1","volume":"105\u2013B","author":"L Knoll","year":"2023","unstructured":"Knoll L, Steppacher SD, Furrer H, Thurnheer-Zurcher MC, Renz N. High treatment failure rate in haematogenous compared to non-haematogenous periprosthetic joint infection. Bone Joint J. 2023;105\u2013B(12):1294\u2013302. https:\/\/doi.org\/10.1302\/0301-620X.105B12.BJJ-2023-0454.R1.","journal-title":"Bone Joint J"},{"issue":"7","key":"970_CR15","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.cmi.2018.10.010","volume":"25","author":"A Rakow","year":"2019","unstructured":"Rakow A, Perka C, Trampuz A, Renz N. Origin and characteristics of haematogenous periprosthetic joint infection. Clin Microbiol Infect. 2019;25(7):845\u201350. https:\/\/doi.org\/10.1016\/j.cmi.2018.10.010.","journal-title":"Clin Microbiol Infect"},{"key":"970_CR16","doi-asserted-by":"publisher","first-page":"101192","DOI":"10.1016\/j.eclinm.2021.101192","volume":"42","author":"AJ Hotchen","year":"2021","unstructured":"Hotchen AJ, Wismayer MG, Robertson-Waters E, McDonnell SM, Kendrick B, Taylor A, et al. The Joint-Specific BACH classification: A predictor of outcome in prosthetic joint infection. EClinicalMedicine. 2021;42:101192. https:\/\/doi.org\/10.1016\/j.eclinm.2021.101192.","journal-title":"EClinicalMedicine"},{"issue":"9","key":"970_CR17","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1016\/j.arth.2024.03.070","volume":"39","author":"NK Kristensen","year":"2024","unstructured":"Kristensen NK, Manning L, Lange J, Davis JS. External Validation of the Joint-Specific Bone Involvement, Antimicrobial Options, Coverage of the Soft Tissues, and Host Status (JS-BACH) Classification for Predicting Outcome in Periprosthetic Joint Infections: A Cohort of 653 Patients. J Arthroplasty. 2024;39(9):2352\u20136. https:\/\/doi.org\/10.1016\/j.arth.2024.03.070.","journal-title":"J Arthroplasty"},{"issue":"6","key":"970_CR18","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1086\/315138","volume":"180","author":"KL Bost","year":"1999","unstructured":"Bost KL, Ramp WK, Nicholson NC, Bento JL, Marriott I, Hudson MC. infection of mouse or human osteoblasts induces high levels of interleukin-6 and interleukin-12 production. J Infect Dis. 1999;180(6):1912\u201320. https:\/\/doi.org\/10.1086\/315138.","journal-title":"J Infect Dis"},{"issue":"3","key":"970_CR19","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/jbmr.1547","volume":"27","author":"J Xiong","year":"2012","unstructured":"Xiong J, O\u2019Brien CA. Osteocyte RANKL: new insights into the control of bone remodeling. J Bone Min Res. 2012;27(3):499\u2013505. https:\/\/doi.org\/10.1002\/jbmr.1547.","journal-title":"J Bone Min Res"},{"key":"970_CR20","doi-asserted-by":"publisher","first-page":"264","DOI":"10.22203\/eCM.v042a19","volume":"42","author":"RT Ormsby","year":"2021","unstructured":"Ormsby RT, Zelmer AR, Yang D, Gunn NJ, Starczak Y, Kidd SP, et al. Evidence for osteocyte-mediated bone-matrix degradation associated with periprosthetic joint infection (PJI). Eur Cell Mater. 2021;42:264\u201380. https:\/\/doi.org\/10.22203\/eCM.v042a19.","journal-title":"Eur Cell Mater"},{"key":"970_CR21","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.mce.2014.10.007","volume":"399","author":"N Ito","year":"2015","unstructured":"Ito N, Wijenayaka AR, Prideaux M, Kogawa M, Ormsby RT, Evdokiou A, et al. Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli. Mol Cell Endocrinol. 2015;399:208\u201318. https:\/\/doi.org\/10.1016\/j.mce.2014.10.007.","journal-title":"Mol Cell Endocrinol"},{"issue":"6","key":"970_CR22","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","volume":"140","author":"O Takeuchi","year":"2010","unstructured":"Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805\u201320. https:\/\/doi.org\/10.1016\/j.cell.2010.01.022.","journal-title":"Cell"},{"issue":"5","key":"970_CR23","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1007\/s10753-012-9477-y","volume":"35","author":"H Cvija","year":"2012","unstructured":"Cvija H, Kovacic N, Katavic V, Ivcevic S, Aguila HL, Marusic A, Grcevic D. Chemotactic and immunoregulatory properties of bone cells are modulated by endotoxin-stimulated lymphocytes. Inflammation. 2012;35(5):1618\u201331. https:\/\/doi.org\/10.1007\/s10753-012-9477-y.","journal-title":"Inflammation"},{"issue":"12","key":"970_CR24","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1902\/jop.1999.70.12.1472","volume":"70","author":"YL Jiang","year":"1999","unstructured":"Jiang YL, Graves DT. Periodontal pathogens stimulate CC-chemokine production by mononuclear and bone-derived cells. J Periodontol. 1999;70(12):1472\u20138. https:\/\/doi.org\/10.1902\/jop.1999.70.12.1472.","journal-title":"J Periodontol"},{"issue":"2","key":"970_CR25","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00418-008-0522-8","volume":"131","author":"D Varoga","year":"2009","unstructured":"Varoga D, Wruck CJ, Tohidnezhad M, Brandenburg L, Paulsen F, Mentlein R, et al. Osteoblasts participate in the innate immunity of the bone by producing human beta defensin-3. Histochem Cell Biol. 2009;131(2):207\u201318. https:\/\/doi.org\/10.1007\/s00418-008-0522-8.","journal-title":"Histochem Cell Biol"},{"key":"970_CR26","doi-asserted-by":"publisher","first-page":"1066237","DOI":"10.3389\/fmicb.2022.1066237","volume":"13","author":"MB Johnson","year":"2022","unstructured":"Johnson MB, Furr KH, Suptela SR, Leach W, Marriott I. Induction of protective interferon-beta responses in murine osteoblasts following Staphylococcus aureus infection. Front Microbiol. 2022;13:1066237. https:\/\/doi.org\/10.3389\/fmicb.2022.1066237.","journal-title":"Front Microbiol"},{"key":"970_CR27","doi-asserted-by":"publisher","first-page":"1138539","DOI":"10.3389\/fimmu.2023.1138539","volume":"14","author":"E Chaumond","year":"2023","unstructured":"Chaumond E, Peron S, Daniel N, Le Gouar Y, Guedon E, Williams DL, et al. Development of innate immune memory by non-immune cells during Staphylococcus aureus infection depends on reactive oxygen species. Front Immunol. 2023;14:1138539. https:\/\/doi.org\/10.3389\/fimmu.2023.1138539.","journal-title":"Front Immunol"},{"key":"970_CR28","doi-asserted-by":"publisher","first-page":"937466","DOI":"10.3389\/fmicb.2022.937466","volume":"13","author":"M Garcia-Moreno","year":"2022","unstructured":"Garcia-Moreno M, Jordan PM, Gunther K, Dau T, Fritzsch C, Vermes M, et al. Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms. Front Microbiol. 2022;13:937466. https:\/\/doi.org\/10.3389\/fmicb.2022.937466.","journal-title":"Front Microbiol"},{"key":"970_CR29","doi-asserted-by":"publisher","first-page":"781022","DOI":"10.3389\/fcimb.2021.781022","volume":"11","author":"NJ Gunn","year":"2021","unstructured":"Gunn NJ, Zelmer AR, Kidd SP, Solomon LB, Roscioli E, Yang D, Atkins GJ. A Human Osteocyte Cell Line Model for Studying Staphylococcus aureus Persistence in Osteomyelitis. Front Cell Infect Microbiol. 2021;11:781022. https:\/\/doi.org\/10.3389\/fcimb.2021.781022.","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"970_CR30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1189\/jlb.0204065","volume":"76","author":"MJ Ruddy","year":"2004","unstructured":"Ruddy MJ, Shen F, Smith JB, Sharma A, Gaffen SL. Interleukin-17 regulates expression of the CXC chemokine LIX\/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment. J Leukoc Biol. 2004;76(1):135\u201344. https:\/\/doi.org\/10.1189\/jlb.0204065.","journal-title":"J Leukoc Biol"},{"issue":"6","key":"970_CR31","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/j.immuni.2016.05.012","volume":"44","author":"A Terashima","year":"2016","unstructured":"Terashima A, Okamoto K, Nakashima T, Akira S, Ikuta K, Takayanagi H. Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency. Immunity. 2016;44(6):1434\u201343. https:\/\/doi.org\/10.1016\/j.immuni.2016.05.012.","journal-title":"Immunity"},{"issue":"12","key":"970_CR32","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1359\/jbmr.1997.12.12.2014","volume":"12","author":"Y Kato","year":"1997","unstructured":"Kato Y, Windle JJ, Koop BA, Mundy GR, Bonewald LF. Establishment of an osteocyte-like cell line, MLO-Y4. J Bone Min Res. 1997;12(12):2014\u201323. https:\/\/doi.org\/10.1359\/jbmr.1997.12.12.2014.","journal-title":"J Bone Min Res"},{"issue":"1","key":"970_CR33","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1083\/jcb.96.1.191","volume":"96","author":"H Sudo","year":"1983","unstructured":"Sudo H, Kodama HA, Amagai Y, Yamamoto S, Kasai S. In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol. 1983;96(1):191\u20138. https:\/\/doi.org\/10.1083\/jcb.96.1.191.","journal-title":"J Cell Biol"},{"issue":"1","key":"970_CR34","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s12985-014-0189-9","volume":"11","author":"W Chen","year":"2014","unstructured":"Chen W, Foo SS, Li RW, Smith PN, Mahalingam S. Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses. Virol J. 2014;11(1):189. https:\/\/doi.org\/10.1186\/s12985-014-0189-9.","journal-title":"Virol J"},{"issue":"1","key":"970_CR35","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s12891-016-1091-y","volume":"17","author":"U Dapunt","year":"2016","unstructured":"Dapunt U, Giese T, Stegmaier S, Moghaddam A, Hansch GM. The osteoblast as an inflammatory cell: production of cytokines in response to bacteria and components of bacterial biofilms. BMC Musculoskelet Disord. 2016;17(1):243. https:\/\/doi.org\/10.1186\/s12891-016-1091-y.","journal-title":"BMC Musculoskelet Disord"},{"key":"970_CR36","doi-asserted-by":"publisher","first-page":"854242","DOI":"10.3389\/fcimb.2022.854242","volume":"12","author":"A Nicolas","year":"2022","unstructured":"Nicolas A, Deplanche M, Commere PH, Diot A, Genthon C, Marques da Silva W, et al. Transcriptome Architecture of Osteoblastic Cells Infected With Staphylococcus aureus Reveals Strong Inflammatory Responses and Signatures of Metabolic and Epigenetic Dysregulation. Front Cell Infect Microbiol. 2022;12:854242. https:\/\/doi.org\/10.3389\/fcimb.2022.854242.","journal-title":"Front Cell Infect Microbiol"},{"issue":"6","key":"970_CR37","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1189\/jlb.0903433","volume":"75","author":"KM Wright","year":"2004","unstructured":"Wright KM, Friedland JS. Regulation of monocyte chemokine and MMP-9 secretion by proinflammatory cytokines in tuberculous osteomyelitis. J Leukoc Biol. 2004;75(6):1086\u201392. https:\/\/doi.org\/10.1189\/jlb.0903433.","journal-title":"J Leukoc Biol"},{"issue":"9","key":"970_CR38","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.micinf.2004.04.008","volume":"6","author":"KM Wright","year":"2004","unstructured":"Wright KM, Friedland JS. Regulation of chemokine gene expression and secretion in Staphylococcus aureus-infected osteoblasts. Microbes Infect. 2004;6(9):844\u201352. https:\/\/doi.org\/10.1016\/j.micinf.2004.04.008.","journal-title":"Microbes Infect"},{"issue":"3","key":"970_CR39","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1128\/IAI.71.3.1209-1216.2003","volume":"71","author":"LW Schrum","year":"2003","unstructured":"Schrum LW, Marriott I, Butler BR, Thomas EK, Hudson MC, Bost KL. Functional CD40 expression induced following bacterial infection of mouse and human osteoblasts. Infect Immun. 2003;71(3):1209\u201316. https:\/\/doi.org\/10.1128\/IAI.71.3.1209-1216.2003.","journal-title":"Infect Immun"},{"key":"970_CR40","doi-asserted-by":"publisher","first-page":"780272","DOI":"10.3389\/fcimb.2022.780272","volume":"12","author":"W Ma","year":"2022","unstructured":"Ma W, Jin W, He X, Sun Y, Yin H, Wang Z, Shi S. Mycobacterium tuberculosis Induced Osteoblast Dysregulation Involved in Bone Destruction in Spinal Tuberculosis. Front Cell Infect Microbiol. 2022;12:780272. https:\/\/doi.org\/10.3389\/fcimb.2022.780272.","journal-title":"Front Cell Infect Microbiol"},{"issue":"9","key":"970_CR41","doi-asserted-by":"publisher","first-page":"e70165","DOI":"10.1111\/acel.70165","volume":"24","author":"AO Gonzalez","year":"2025","unstructured":"Gonzalez AO, Abdul Azees PA, Chen JP, Marinkovic M, Cao B, Liang T, et al. Aging Adipose-Derived Mesenchymal Stem Cells, Cultured on a Native Young Extracellular Matrix, Are Protected From Senescence and Apoptosis Along With Increased Expression of HLA-DR and CD74 Associated With PI3K Signaling. Aging Cell. 2025;24(9):e70165. https:\/\/doi.org\/10.1111\/acel.70165.","journal-title":"Aging Cell"},{"issue":"1","key":"970_CR42","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1146\/annurev-immunol-032712-095910","volume":"31","author":"JS Blum","year":"2013","unstructured":"Blum JS, Wearsch PA, Cresswell P. Pathways of antigen processing. Annu Rev Immunol. 2013;31(1):443\u201373.","journal-title":"Annu Rev Immunol"},{"issue":"12","key":"970_CR43","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nri3084","volume":"11","author":"J Neefjes","year":"2011","unstructured":"Neefjes J, Jongsma ML, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11(12):823\u201336.","journal-title":"Nat Rev Immunol"},{"issue":"4","key":"970_CR44","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nri3818","volume":"15","author":"PA Roche","year":"2015","unstructured":"Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015;15(4):203\u201316.","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"970_CR45","doi-asserted-by":"publisher","first-page":"5075","DOI":"10.1128\/IAI.68.9.5075-5083.2000","volume":"68","author":"KL Bost","year":"2000","unstructured":"Bost KL, Bento JL, Ellington JK, Marriott I, Hudson MC. Induction of colony-stimulating factor expression following Staphylococcus or Salmonella interaction with mouse or human osteoblasts. Infect Immun. 2000;68(9):5075\u201383. https:\/\/doi.org\/10.1128\/IAI.68.9.5075-5083.2000.","journal-title":"Infect Immun"},{"issue":"4","key":"970_CR46","doi-asserted-by":"publisher","first-page":"ftw030","DOI":"10.1093\/femspd\/ftw030","volume":"74","author":"AR Munoz-Duarte","year":"2016","unstructured":"Munoz-Duarte AR, Castrejon-Jimenez NS, Baltierra-Uribe SL, Perez-Rangel SJ, Carapia-Minero N, Castaneda-Sanchez JI, et al. Candida glabrata survives and replicates in human osteoblasts. FEMS Pathogens Disease. 2016;74(4):ftw030.","journal-title":"FEMS Pathogens Disease"},{"issue":"4","key":"970_CR47","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1016\/S0002-9440(10)63226-9","volume":"164","author":"I Marriott","year":"2004","unstructured":"Marriott I, Gray DL, Tranguch SL, Fowler VG Jr., Stryjewski M, Scott Levin L, et al. Osteoblasts express the inflammatory cytokine interleukin-6 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. Am J Pathol. 2004;164(4):1399\u2013406. https:\/\/doi.org\/10.1016\/S0002-9440(10)63226-9.","journal-title":"Am J Pathol"},{"issue":"5","key":"970_CR48","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.1128\/IAI.73.5.2967-2973.2005","volume":"73","author":"I Marriott","year":"2005","unstructured":"Marriott I, Rati DM, McCall SH, Tranguch SL. Induction of Nod1 and Nod2 intracellular pattern recognition receptors in murine osteoblasts following bacterial challenge. Infect Immun. 2005;73(5):2967\u201373. https:\/\/doi.org\/10.1128\/IAI.73.5.2967-2973.2005.","journal-title":"Infect Immun"},{"issue":"1","key":"970_CR49","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.molimm.2012.04.005","volume":"52","author":"L Die","year":"2012","unstructured":"Die L, Yan P, Jun Jiang Z, Min Hua T, Cai W, Xing L. Glycogen synthase kinase-3 beta inhibitor suppresses Porphyromonas gingivalis lipopolysaccharide-induced CD40 expression by inhibiting nuclear factor-kappa B activation in mouse osteoblasts. Mol Immunol. 2012;52(1):38\u201349. https:\/\/doi.org\/10.1016\/j.molimm.2012.04.005.","journal-title":"Mol Immunol"},{"issue":"4","key":"970_CR50","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1002\/eji.200425891","volume":"35","author":"K Hochweller","year":"2005","unstructured":"Hochweller K, Anderton SM. Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo. Eur J Immunol. 2005;35(4):1086\u201396. https:\/\/doi.org\/10.1002\/eji.200425891.","journal-title":"Eur J Immunol"},{"issue":"1","key":"970_CR51","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1196\/annals.1288.014","volume":"1005","author":"AE Juedes","year":"2003","unstructured":"Juedes AE, Von Herrath MG. Using regulatory APCs to induce\/maintain tolerance. Ann N Y Acad Sci. 2003;1005(1):128\u201337. https:\/\/doi.org\/10.1196\/annals.1288.014.","journal-title":"Ann N Y Acad Sci"},{"key":"970_CR52","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3389\/fimmu.2013.00082","volume":"4","author":"M Hubo","year":"2013","unstructured":"Hubo M, Trinschek B, Kryczanowsky F, Tuettenberg A, Steinbrink K, Jonuleit H. Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells. Front Immunol. 2013;4:82. https:\/\/doi.org\/10.3389\/fimmu.2013.00082.","journal-title":"Front Immunol"},{"issue":"3","key":"970_CR53","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.coi.2010.02.013","volume":"22","author":"JM Curtsinger","year":"2010","unstructured":"Curtsinger JM, Mescher MF. Inflammatory cytokines as a third signal for T cell activation. Curr Opin Immunol. 2010;22(3):333\u201340. https:\/\/doi.org\/10.1016\/j.coi.2010.02.013.","journal-title":"Curr Opin Immunol"},{"issue":"7090","key":"970_CR54","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature04753","volume":"441","author":"E Bettelli","year":"2006","unstructured":"Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235\u20138. https:\/\/doi.org\/10.1038\/nature04753.","journal-title":"Nature"},{"issue":"5609","key":"970_CR55","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1126\/science.1078231","volume":"299","author":"C Pasare","year":"2003","unstructured":"Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4\u2009+\u2009CD25+ T cell-mediated suppression by dendritic cells. Science. 2003;299(5609):1033\u20136. https:\/\/doi.org\/10.1126\/science.1078231.","journal-title":"Science"},{"issue":"2","key":"970_CR56","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/s8756-3282(00)00421-x","volume":"28","author":"H Kamioka","year":"2001","unstructured":"Kamioka H, Honjo T, Takano-Yamamoto T. A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy. Bone. 2001;28(2):145\u20139. https:\/\/doi.org\/10.1016\/s8756-3282(00)00421-x.","journal-title":"Bone"},{"issue":"5","key":"970_CR57","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/jbmr.3055","volume":"32","author":"KL de Mesy Bentley","year":"2017","unstructured":"de Mesy Bentley KL, Trombetta R, Nishitani K, Bello-Irizarry SN, Ninomiya M, Zhang L, et al. Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis. J Bone Min Res. 2017;32(5):985\u201390. https:\/\/doi.org\/10.1002\/jbmr.3055.","journal-title":"J Bone Min Res"},{"issue":"9","key":"970_CR58","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1359\/jbmr.2002.17.9.1680","volume":"17","author":"KM Wright","year":"2002","unstructured":"Wright KM, Friedland JS. Differential regulation of chemokine secretion in tuberculous and staphylococcal osteomyelitis. J Bone Min Res. 2002;17(9):1680\u201390. https:\/\/doi.org\/10.1359\/jbmr.2002.17.9.1680.","journal-title":"J Bone Min Res"},{"issue":"10","key":"970_CR59","doi-asserted-by":"publisher","first-page":"e0080824","DOI":"10.1128\/aac.00808-24","volume":"68","author":"AR Zelmer","year":"2024","unstructured":"Zelmer AR, Yang D, Gunn NJ, Solomon LB, Nelson R, Kidd SP, et al. Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular S. aureus infections in osteocytes. Antimicrob Agents Chemother. 2024;68(10):e0080824. https:\/\/doi.org\/10.1128\/aac.00808-24.","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"970_CR60","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41413-022-00227-8","volume":"10","author":"AR Zelmer","year":"2022","unstructured":"Zelmer AR, Nelson R, Richter K, Atkins GJ. Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis. Bone Res. 2022;10(1):53. https:\/\/doi.org\/10.1038\/s41413-022-00227-8.","journal-title":"Bone Res"},{"key":"970_CR61","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.actbio.2019.01.047","volume":"87","author":"RT Ormsby","year":"2019","unstructured":"Ormsby RT, Solomon LB, Yang D, Crotti TN, Haynes DR, Findlay DM, Atkins GJ. Osteocytes respond to particles of clinically-relevant conventional and cross-linked polyethylene and metal alloys by up-regulation of resorptive and inflammatory pathways. Acta Biomater. 2019;87:296\u2013306. https:\/\/doi.org\/10.1016\/j.actbio.2019.01.047.","journal-title":"Acta Biomater"},{"key":"970_CR62","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.actbio.2016.01.016","volume":"33","author":"RT Ormsby","year":"2016","unstructured":"Ormsby RT, Cantley M, Kogawa M, Solomon LB, Haynes DR, Findlay DM, Atkins GJ. Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis. Acta Biomater. 2016;33:242\u201351. https:\/\/doi.org\/10.1016\/j.actbio.2016.01.016.","journal-title":"Acta Biomater"},{"key":"970_CR63","doi-asserted-by":"publisher","unstructured":"Goodman SB, Gallo J Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment. J Clin Med. 2019;8(12). https:\/\/doi.org\/10.3390\/jcm8122091.","DOI":"10.3390\/jcm8122091"},{"issue":"6","key":"970_CR64","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.ajpath.2020.02.007","volume":"190","author":"MI Hofstee","year":"2020","unstructured":"Hofstee MI, Muthukrishnan G, Atkins GJ, Riool M, Thompson K, Morgenstern M, et al. Current Concepts of Osteomyelitis: From Pathologic Mechanisms to Advanced Research Methods. Am J Pathol. 2020;190(6):1151\u201363. https:\/\/doi.org\/10.1016\/j.ajpath.2020.02.007.","journal-title":"Am J Pathol"},{"issue":"3","key":"970_CR65","first-page":"189","volume":"15","author":"RD Ning","year":"2011","unstructured":"Ning RD, Zhang XL, Guo XK, Li QT. regulates secretion of interleukin-6 and monocyte chemoattractant protein-1 through activation of nuclear factor kappaB signaling pathway in human osteoblasts. Braz J Infect Dis. 2011;15(3):189\u201394.","journal-title":"Braz J Infect Dis"},{"issue":"1 Pt 1","key":"970_CR66","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.jfma.2020.04.010","volume":"120","author":"HH Lin","year":"2021","unstructured":"Lin HH, Lin YW, Wu CY, Hsiao FP, Lai YL, Hung SL. Stimulatory effects of Porphyromonas gingivalis GroEL protein on interleukin-6 and interleukin-8 in human osteoblasts. J Formos Med Assoc. 2021;120(1 Pt 1):150\u20136. https:\/\/doi.org\/10.1016\/j.jfma.2020.04.010.","journal-title":"J Formos Med Assoc"},{"issue":"8","key":"970_CR67","doi-asserted-by":"publisher","first-page":"4075","DOI":"10.1128\/IAI.70.8.4075-4082.2002","volume":"70","author":"NA Gasper","year":"2002","unstructured":"Gasper NA, Petty CC, Schrum LW, Marriott I, Bost KL. Bacterium-induced CXCL10 secretion by osteoblasts can be mediated in part through toll-like receptor 4. Infect Immun. 2002;70(8):4075\u201382. https:\/\/doi.org\/10.1128\/IAI.70.8.4075-4082.2002.","journal-title":"Infect Immun"},{"issue":"Pt 7","key":"970_CR68","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1099\/jmm.0.015859-0","volume":"59","author":"VS Chauhan","year":"2010","unstructured":"Chauhan VS, Marriott I. Differential roles for NOD2 in osteoblast inflammatory immune responses to bacterial pathogens of bone tissue. J Med Microbiol. 2010;59(Pt 7):755\u201362. https:\/\/doi.org\/10.1099\/jmm.0.015859-0.","journal-title":"J Med Microbiol"},{"issue":"6","key":"970_CR69","doi-asserted-by":"publisher","first-page":"e0156708","DOI":"10.1371\/journal.pone.0156708","volume":"11","author":"A Kassem","year":"2016","unstructured":"Kassem A, Lindholm C, Lerner UH. Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL. PLoS ONE. 2016;11(6):e0156708. https:\/\/doi.org\/10.1371\/journal.pone.0156708.","journal-title":"PLoS ONE"},{"issue":"1","key":"970_CR70","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3390\/biom11010072","volume":"11","author":"N Musso","year":"2021","unstructured":"Musso N, Caruso G, Bongiorno D, Grasso M, Bivona DA, Campanile F, et al. Different Modulatory Effects of Four Methicillin-Resistant Staphylococcus aureus Clones on MG-63 Osteoblast-Like Cells. Biomolecules. 2021;11(1):72. https:\/\/doi.org\/10.3390\/biom11010072.","journal-title":"Biomolecules"},{"issue":"8","key":"970_CR71","doi-asserted-by":"publisher","first-page":"e13204","DOI":"10.1111\/cmi.13204","volume":"22","author":"E Lima Leite","year":"2020","unstructured":"Lima Leite E, Gautron A, Deplanche M, Nicolas A, Ossemond J, Nguyen MT, et al. Involvement of caspase-1 in inflammasomes activation and bacterial clearance in S. aureus-infected osteoblast-like MG-63 cells. Cell Microbiol. 2020;22(8):e13204. https:\/\/doi.org\/10.1111\/cmi.13204.","journal-title":"Cell Microbiol"},{"key":"970_CR72","doi-asserted-by":"publisher","first-page":"102762","DOI":"10.1016\/j.nano.2024.102762","volume":"60","author":"EL Mills","year":"2024","unstructured":"Mills EL, Avila YI, Beasock D, Radwan Y, Suptela SR, Marriott I, et al. Immunostimulatory nucleic acid nanoparticles (NANPs) augment protective osteoblast and osteoclast type I interferon responses to Staphylococcus aureus. Nanomedicine. 2024;60:102762. https:\/\/doi.org\/10.1016\/j.nano.2024.102762.","journal-title":"Nanomedicine"},{"issue":"33","key":"970_CR73","doi-asserted-by":"publisher","first-page":"20147","DOI":"10.1074\/jbc.M115.655787","volume":"290","author":"A Kassem","year":"2015","unstructured":"Kassem A, Henning P, Lundberg P, Souza PPC, Lindholm C, Lerner UH. Stimulates Bone Resorption by Enhancing RANKL (Receptor Activator of NF-\u03baB Ligand) through Activation of Toll-like Receptor 2 in Osteoblasts. J Biol Chem. 2015;290(33):20147\u201358. https:\/\/doi.org\/10.1074\/jbc.M115.655787.","journal-title":"J Biol Chem"},{"key":"970_CR74","doi-asserted-by":"publisher","unstructured":"Morita Y, Saito M, Rangel-Moreno J, Franchini AM, Owen JR, Martinez JC et al. Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation. Bone Research. 2022;10(1):56. https:\/\/doi.org\/10.1038\/s41413-022-00228-7.","DOI":"10.1038\/s41413-022-00228-7"},{"issue":"4","key":"970_CR76","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1111\/omi.12022","volume":"28","author":"C Jauregui","year":"2013","unstructured":"Jauregui C, Mansell JP, Jepson MA, Jenkinson HF. Differential interactions of S treptococcus gordonii and S taphylococcus aureus with cultured osteoblasts. Mol oral Microbiol. 2013;28(4):250\u201366.","journal-title":"Mol oral Microbiol"},{"issue":"4","key":"970_CR77","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.micinf.2005.10.021","volume":"8","author":"T Ohno","year":"2006","unstructured":"Ohno T, Okahashi N, Kawai S, Kato T, Inaba H, Shibata Y, et al. Proinflammatory gene expression in mouse ST2 cell line in response to infection by Porphyromonas gingivalis. Microbes Infect. 2006;8(4):1025\u201334. https:\/\/doi.org\/10.1016\/j.micinf.2005.10.021.","journal-title":"Microbes Infect"},{"issue":"1","key":"970_CR78","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1007\/s10753-022-01731-z","volume":"46","author":"MB Johnson","year":"2023","unstructured":"Johnson MB, Suptela SR, Sipprell SE, Marriott I. Substance P Exacerbates the Inflammatory and Pro-osteoclastogenic Responses of Murine Osteoclasts and Osteoblasts to Staphylococcus aureus. Inflammation. 2023;46(1):256\u201369. https:\/\/doi.org\/10.1007\/s10753-022-01731-z.","journal-title":"Inflammation"},{"issue":"4","key":"970_CR79","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.bone.2005.05.011","volume":"37","author":"I Marriott","year":"2005","unstructured":"Marriott I, Gray DL, Rati DM, Fowler VG Jr., Stryjewski ME, Levin LS, et al. Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. Bone. 2005;37(4):504\u201312. https:\/\/doi.org\/10.1016\/j.bone.2005.05.011.","journal-title":"Bone"}],"container-title":["Current Osteoporosis Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11914-026-00970-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11914-026-00970-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11914-026-00970-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:17:47Z","timestamp":1778563067000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11914-026-00970-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["970"],"URL":"https:\/\/doi.org\/10.1007\/s11914-026-00970-5","relation":{},"ISSN":["1544-2241"],"issn-type":[{"value":"1544-2241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"1 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"G.J.A. is an Inventor on PCT Patent PCT\/AU2025\/050524, Histological Markers and Methods For Analysis of Bone Matrix Integrity. None of the other authors has any competing interests to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"22"}}