{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T10:43:08Z","timestamp":1793788988027,"version":"4.6.1"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K01AR070328"],"award-info":[{"award-number":["K01AR070328"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR064251"],"award-info":[{"award-number":["R01AR064251"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR060364"],"award-info":[{"award-number":["R01AR060364"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006380","name":"Rehabilitation Research and Development Service","doi-asserted-by":"publisher","award":["RX001757"],"award-info":[{"award-number":["RX001757"]}],"id":[{"id":"10.13039\/100006380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Semin Immunopathol"],"published-print":{"date-parts":[[2019,9]]},"DOI":"10.1007\/s00281-019-00762-3","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T13:13:34Z","timestamp":1571058814000},"page":"583-594","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["An emerging role for Toll-like receptors at the neuroimmune interface in osteoarthritis"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4486-5757","authenticated-orcid":false,"given":"Rachel E.","family":"Miller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-188X","authenticated-orcid":false,"given":"Carla R.","family":"Scanzello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-0384","authenticated-orcid":false,"given":"Anne-Marie","family":"Malfait","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,14]]},"reference":[{"issue":"10100","key":"762_CR1","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/S0140-6736(17)32154-2","volume":"390","author":"Collaborators GDaIIaP","year":"2017","unstructured":"Collaborators GDaIIaP (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390(10100):1211\u20131259","journal-title":"Lancet"},{"issue":"5","key":"762_CR2","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.semarthrit.2014.10.012","volume":"44","author":"J Puig-Junoy","year":"2015","unstructured":"Puig-Junoy J, Ruiz Zamora A (2015) Socio-economic costs of osteoarthritis: a systematic review of cost-of-illness studies. Semin Arthritis Rheum 44(5):531\u2013541","journal-title":"Semin Arthritis Rheum"},{"issue":"3","key":"762_CR3","doi-asserted-by":"publisher","first-page":"e91286","DOI":"10.1371\/journal.pone.0091286","volume":"9","author":"GA Hawker","year":"2014","unstructured":"Hawker GA, Croxford R, Bierman AS, Harvey PJ, Ravi B, Stanaitis I, Lipscombe LL (2014) All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study. PLoS One 9(3):e91286","journal-title":"PLoS One"},{"issue":"5","key":"762_CR4","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.berh.2012.07.014","volume":"26","author":"B Ravi","year":"2012","unstructured":"Ravi B, Croxford R, Reichmann WM, Losina E, Katz JN, Hawker GA (2012) The changing demographics of total joint arthroplasty recipients in the United States and Ontario from 2001 to 2007. Best Pract Res Clin Rheumatol 26(5):637\u2013647","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"2","key":"762_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2519\/jospt.2017.7286","volume":"47","author":"IN Ackerman","year":"2017","unstructured":"Ackerman IN, Kemp JL, Crossley KM, Culvenor AG, Hinman RS (2017) Hip and knee osteoarthritis affects younger people, too. J Orthop Sports Phys Ther 47(2):67\u201379","journal-title":"J Orthop Sports Phys Ther"},{"issue":"11","key":"762_CR6","doi-asserted-by":"publisher","first-page":"3368","DOI":"10.1016\/j.arth.2017.05.052","volume":"32","author":"F Castagnini","year":"2017","unstructured":"Castagnini F, Sudanese A, Bordini B, Tassinari E, Stea S, Toni A (2017) Total knee replacement in young patients: survival and causes of revision in a registry population. J Arthroplast 32(11):3368\u20133372","journal-title":"J Arthroplast"},{"issue":"3","key":"762_CR7","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3899\/jrheum.140382","volume":"42","author":"EW Orlowsky","year":"2015","unstructured":"Orlowsky EW, Kraus VB (2015) The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol 42(3):363\u2013371","journal-title":"J Rheumatol"},{"issue":"1","key":"762_CR8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/BOR.0000000000000353","volume":"29","author":"CR Scanzello","year":"2017","unstructured":"Scanzello CR (2017) Role of low-grade inflammation in osteoarthritis. Curr Opin Rheumatol 29(1):79\u201385","journal-title":"Curr Opin Rheumatol"},{"issue":"2","key":"762_CR9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11926-018-0716-6","volume":"20","author":"D Syx","year":"2018","unstructured":"Syx D, Tran PB, Miller RE, Malfait AM (2018) Peripheral mechanisms contributing to osteoarthritis pain. Curr Rheumatol Rep 20(2):9","journal-title":"Curr Rheumatol Rep"},{"issue":"5","key":"762_CR10","first-page":"75","volume":"35 Suppl 107","author":"T Neogi","year":"2017","unstructured":"Neogi T (2017) Structural correlates of pain in osteoarthritis. Clin Exp Rheumatol 35 Suppl 107(5):75\u201378","journal-title":"Clin Exp Rheumatol"},{"issue":"2","key":"762_CR11","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.cell.2009.09.028","volume":"139","author":"AI Basbaum","year":"2009","unstructured":"Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139(2):267\u2013284","journal-title":"Cell"},{"issue":"1","key":"762_CR12","first-page":"172","volume":"36","author":"SA Woller","year":"2018","unstructured":"Woller SA, Eddinger KA, Corr M, Yaksh TL (2018) An overview of pathways encoding nociception. Clin Exp Rheumatol 36(1):172","journal-title":"Clin Exp Rheumatol"},{"issue":"1","key":"762_CR13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s00540-018-2579-4","volume":"33","author":"M Matsuda","year":"2019","unstructured":"Matsuda M, Huh Y, Ji RR (2019) Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain. J Anesth 33(1):131\u2013139","journal-title":"J Anesth"},{"key":"762_CR14","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev-neuro-072116-031121","volume":"40","author":"F Denk","year":"2017","unstructured":"Denk F, Bennett DL, McMahon SB (2017) Nerve growth factor and pain mechanisms. Annu Rev Neurosci 40:307\u2013325","journal-title":"Annu Rev Neurosci"},{"issue":"1","key":"762_CR15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.it.2016.10.001","volume":"38","author":"FA Pinho-Ribeiro","year":"2017","unstructured":"Pinho-Ribeiro FA, Verri WA Jr, Chiu IM (2017) Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol 38(1):5\u201319","journal-title":"Trends Immunol"},{"issue":"50","key":"762_CR16","doi-asserted-by":"publisher","first-page":"20602","DOI":"10.1073\/pnas.1209294110","volume":"109","author":"RE Miller","year":"2012","unstructured":"Miller RE, Tran PB, Das R, Ghoreishi-Haack N, Ren D, Miller RJ, Malfait AM (2012) CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis. Proc Natl Acad Sci U S A 109(50):20602\u201320607","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"762_CR17","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nrrheum.2016.162","volume":"12","author":"M Nefla","year":"2016","unstructured":"Nefla M, Holzinger D, Berenbaum F, Jacques C (2016) The danger from within: alarmins in arthritis. Nat Rev Rheumatol 12(11):669\u2013683","journal-title":"Nat Rev Rheumatol"},{"key":"762_CR18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.pharmthera.2017.10.006","volume":"184","author":"MJ Lacagnina","year":"2018","unstructured":"Lacagnina MJ, Watkins LR, Grace PM (2018) Toll-like receptors and their role in persistent pain. Pharmacol Ther 184:145\u2013158","journal-title":"Pharmacol Ther"},{"key":"762_CR19","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","volume":"5","author":"T Kawasaki","year":"2014","unstructured":"Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:461","journal-title":"Front Immunol"},{"issue":"2","key":"762_CR20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1177\/1759720X12467868","volume":"5","author":"J Sokolove","year":"2013","unstructured":"Sokolove J, Lepus CM (2013) Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis 5(2):77\u201394","journal-title":"Ther Adv Musculoskelet Dis"},{"issue":"2","key":"762_CR21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/cei.13237","volume":"195","author":"MHJ van den Bosch","year":"2019","unstructured":"van den Bosch MHJ (2019) Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease? Clin Exp Immunol 195(2):153\u2013166","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"762_CR22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nrrheum.2014.209","volume":"11","author":"R Gomez","year":"2015","unstructured":"Gomez R, Villalvilla A, Largo R, Gualillo O, Herrero-Beaumont G (2015) TLR4 signalling in osteoarthritis--finding targets for candidate DMOADs. Nat Rev Rheumatol 11(3):159\u2013170","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"762_CR23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1097\/BOR.0b013e3283432d1f","volume":"23","author":"AK Rosenthal","year":"2011","unstructured":"Rosenthal AK (2011) Crystals, inflammation, and osteoarthritis. Curr Opin Rheumatol 23(2):170\u2013173","journal-title":"Curr Opin Rheumatol"},{"issue":"11","key":"762_CR24","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.1002\/art.39291","volume":"67","author":"RE Miller","year":"2015","unstructured":"Miller RE, Belmadani A, Ishihara S, Tran PB, Ren D, Miller RJ, Malfait AM (2015) Damage-associated molecular patterns generated in osteoarthritis directly excite murine nociceptive neurons through Toll-like receptor 4. Arthritis Rheumatol 67(11):2933\u20132943","journal-title":"Arthritis Rheumatol"},{"issue":"1","key":"762_CR25","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1177\/154405910608500108","volume":"85","author":"R Wadachi","year":"2006","unstructured":"Wadachi R, Hargreaves KM (2006) Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. J Dent Res 85(1):49\u201353","journal-title":"J Dent Res"},{"issue":"6","key":"762_CR26","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.pharep.2016.08.006","volume":"68","author":"AT Guerrero","year":"2016","unstructured":"Guerrero AT, Pinto LG, Cunha FQ, Ferreira SH, Alves-Filho JC, Verri WA Jr, Cunha TM (2016) Mechanisms underlying the hyperalgesic responses triggered by joint activation of TLR4. Pharmacol Rep 68(6):1293\u20131300","journal-title":"Pharmacol Rep"},{"issue":"1","key":"762_CR27","doi-asserted-by":"publisher","first-page":"16","DOI":"10.2174\/138920108783497622","volume":"9","author":"MD Tortorella","year":"2008","unstructured":"Tortorella MD, Malfait AM (2008) Will the real aggrecanase(s) step up: evaluating the criteria that define aggrecanase activity in osteoarthritis. Curr Pharm Biotechnol 9(1):16\u201323","journal-title":"Curr Pharm Biotechnol"},{"issue":"24","key":"762_CR28","doi-asserted-by":"publisher","first-page":"15579","DOI":"10.1016\/S0021-9258(18)98442-5","volume":"266","author":"AJ Fosang","year":"1991","unstructured":"Fosang AJ, Neame PJ, Hardingham TE, Murphy G, Hamilton JA (1991) Cleavage of cartilage proteoglycan between G1 and G2 domains by stromelysins. J Biol Chem 266(24):15579\u201315582","journal-title":"J Biol Chem"},{"issue":"5","key":"762_CR29","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1002\/art.39063","volume":"67","author":"S Lees","year":"2015","unstructured":"Lees S, Golub SB, Last K, Zeng W, Jackson DC, Sutton P, Fosang AJ (2015) Bioactivity in an aggrecan 32-mer fragment is mediated via Toll-like receptor 2. Arthritis Rheumatol 67(5):1240\u20131249","journal-title":"Arthritis Rheumatol"},{"issue":"6","key":"762_CR30","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1172\/JCI30765","volume":"117","author":"CB Little","year":"2007","unstructured":"Little CB, Meeker CT, Golub SB, Lawlor KE, Farmer PJ, Smith SM, Fosang AJ (2007) Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair. J Clin Invest 117(6):1627\u20131636","journal-title":"J Clin Invest"},{"key":"762_CR31","first-page":"6","volume":"3","author":"RE Miller","year":"2018","unstructured":"Miller RE, Ishihara S, Tran PB, Golub SB, Last K, Miller RJ, Fosang AJ, Malfait AM (2018) An aggrecan fragment drives osteoarthritis pain through Toll-like receptor 2. JCI Insight 3:6","journal-title":"JCI Insight"},{"issue":"8","key":"762_CR32","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1172\/JCI23755","volume":"115","author":"L Schaefer","year":"2005","unstructured":"Schaefer L, Babelova A, Kiss E, Hausser HJ, Baliova M, Krzyzankova M, Marsche G, Young MF, Mihalik D, Gotte M et al (2005) The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest 115(8):2223\u20132233","journal-title":"J Clin Invest"},{"key":"762_CR33","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.matbio.2013.12.003","volume":"35","author":"J Zeng-Brouwers","year":"2014","unstructured":"Zeng-Brouwers J, Beckmann J, Nastase MV, Iozzo RV, Schaefer L (2014) De novo expression of circulating biglycan evokes an innate inflammatory tissue response via MyD88\/TRIF pathways. Matrix Biol 35:132\u2013142","journal-title":"Matrix Biol"},{"key":"762_CR34","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1186\/s13075-015-0902-0","volume":"17","author":"G Barreto","year":"2015","unstructured":"Barreto G, Soininen A, Ylinen P, Sandelin J, Konttinen YT, Nordstrom DC, Eklund KK (2015) Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis. Arthritis Res Ther 17:379","journal-title":"Arthritis Res Ther"},{"key":"762_CR35","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.abb.2018.01.007","volume":"640","author":"A Avenoso","year":"2018","unstructured":"Avenoso A, D'Ascola A, Scuruchi M, Mandraffino G, Calatroni A, Saitta A, Campo S, Campo GM (2018) The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in human chondrocytes: inhibition by specific siRNA and high polymerized Hyaluronan. Arch Biochem Biophys 640:75\u201382","journal-title":"Arch Biochem Biophys"},{"issue":"3","key":"762_CR36","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.kint.2018.10.037","volume":"95","author":"C Poluzzi","year":"2019","unstructured":"Poluzzi C, Nastase MV, Zeng-Brouwers J, Roedig H, Hsieh LT, Michaelis JB, Buhl EM, Rezende F, Manavski Y, Bleich A et al (2019) Biglycan evokes autophagy in macrophages via a novel CD44\/Toll-like receptor 4 signaling axis in ischemia\/reperfusion injury. Kidney Int 95(3):540\u2013562","journal-title":"Kidney Int"},{"key":"762_CR37","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1111\/febs.14791","volume":"286","author":"H Roedig","year":"2019","unstructured":"Roedig H, Nastase MV, Wygrecka M, Schaefer L (2019) Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy. FEBS J 286:2965\u20132979","journal-title":"FEBS J"},{"issue":"3","key":"762_CR38","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1172\/JCI59643","volume":"122","author":"A Sica","year":"2012","unstructured":"Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122(3):787\u2013795","journal-title":"J Clin Invest"},{"issue":"2","key":"762_CR39","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.joca.2012.10.016","volume":"21","author":"PS Chockalingam","year":"2013","unstructured":"Chockalingam PS, Glasson SS, Lohmander LS (2013) Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation. Osteoarthr Cartil 21(2):339\u2013345","journal-title":"Osteoarthr Cartil"},{"issue":"7","key":"762_CR40","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/nm.1987","volume":"15","author":"K Midwood","year":"2009","unstructured":"Midwood K, Sacre S, Piccinini AM, Inglis J, Trebaul A, Chan E, Drexler S, Sofat N, Kashiwagi M, Orend G, Brennan F, Foxwell B (2009) Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med 15(7):774\u2013780","journal-title":"Nat Med"},{"issue":"1","key":"762_CR41","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1038\/s41467-017-01718-7","volume":"8","author":"L Zuliani-Alvarez","year":"2017","unstructured":"Zuliani-Alvarez L, Marzeda AM, Deligne C, Schwenzer A, McCann FE, Marsden BD, Piccinini AM, Midwood KS (2017) Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nat Commun 8(1):1595","journal-title":"Nat Commun"},{"issue":"6","key":"762_CR42","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.joca.2009.08.013","volume":"18","author":"N Okamura","year":"2010","unstructured":"Okamura N, Hasegawa M, Nakoshi Y, Iino T, Sudo A, Imanaka-Yoshida K, Yoshida T, Uchida A (2010) Deficiency of tenascin-C delays articular cartilage repair in mice. Osteoarthr Cartil 18(6):839\u2013848","journal-title":"Osteoarthr Cartil"},{"issue":"1","key":"762_CR43","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1177\/1947603516681134","volume":"9","author":"Y Matsui","year":"2018","unstructured":"Matsui Y, Hasegawa M, Iino T, Imanaka-Yoshida K, Yoshida T, Sudo A (2018) Tenascin-C prevents articular cartilage degeneration in murine osteoarthritis models. Cartilage 9(1):80\u201388","journal-title":"Cartilage"},{"key":"762_CR44","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.ejphar.2016.06.039","volume":"788","author":"J Kato","year":"2016","unstructured":"Kato J, Agalave NM, Svensson CI (2016) Pattern recognition receptors in chronic pain: mechanisms and therapeutic implications. Eur J Pharmacol 788:261\u2013273","journal-title":"Eur J Pharmacol"},{"key":"762_CR45","doi-asserted-by":"publisher","first-page":"28188","DOI":"10.1038\/srep28188","volume":"6","author":"XJ Liu","year":"2016","unstructured":"Liu XJ, Liu T, Chen G, Wang B, Yu XL, Yin C, Ji RR (2016) TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation. Sci Rep 6:28188","journal-title":"Sci Rep"},{"issue":"4","key":"762_CR46","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.jbspin.2014.01.018","volume":"81","author":"S Nasi","year":"2014","unstructured":"Nasi S, Ea HK, Chobaz V, van Lent P, Liote F, So A, Busso N (2014) Dispensable role of myeloid differentiation primary response gene 88 (MyD88) and MyD88-dependent toll-like receptors (TLRs) in a murine model of osteoarthritis. Joint Bone Spine 81(4):320\u2013324","journal-title":"Joint Bone Spine"},{"key":"762_CR47","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/1742-2094-10-148","volume":"10","author":"JA Stokes","year":"2013","unstructured":"Stokes JA, Cheung J, Eddinger K, Corr M, Yaksh TL (2013) Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice. J Neuroinflammation 10:148","journal-title":"J Neuroinflammation"},{"issue":"12","key":"762_CR48","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1016\/j.pain.2011.09.020","volume":"152","author":"CA Christianson","year":"2011","unstructured":"Christianson CA, Dumlao DS, Stokes JA, Dennis EA, Svensson CI, Corr M, Yaksh TL (2011) Spinal TLR4 mediates the transition to a persistent mechanical hypersensitivity after the resolution of inflammation in serum-transferred arthritis. Pain 152(12):2881\u20132891","journal-title":"Pain"},{"issue":"11","key":"762_CR49","doi-asserted-by":"publisher","first-page":"e0206217","DOI":"10.1371\/journal.pone.0206217","volume":"13","author":"N Sambamurthy","year":"2018","unstructured":"Sambamurthy N, Zhou C, Nguyen V, Smalley R, Hankenson KD, Dodge GR, Scanzello CR (2018) Deficiency of the pattern-recognition receptor CD14 protects against joint pathology and functional decline in a murine model of osteoarthritis. PLoS One 13(11):e0206217","journal-title":"PLoS One"},{"issue":"10","key":"762_CR50","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1002\/art.23870","volume":"58","author":"JJ Inglis","year":"2008","unstructured":"Inglis JJ, McNamee KE, Chia SL, Essex D, Feldmann M, Williams RO, Hunt SP, Vincent T (2008) Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system. Arthritis Rheum 58(10):3110\u20133119","journal-title":"Arthritis Rheum"},{"key":"762_CR51","unstructured":"Blom AB, van Lent PL, Abdollahi-Roodsaz S, van der Kraan PM, van den Berg WB: Toll like receptor-2 prevents cartilage damage in osteoarthritis models that display synovial activation. In: Orthopaedic Research Society annual meeting. San Francisco; 2012"},{"issue":"1","key":"762_CR52","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1136\/annrheumdis-2014-205480","volume":"75","author":"RF Schelbergen","year":"2016","unstructured":"Schelbergen RF, de Munter W, van den Bosch MH, Lafeber FP, Sloetjes A, Vogl T, Roth J, van den Berg WB, van der Kraan PM, Blom AB et al (2016) Alarmins S100A8\/S100A9 aggravate osteophyte formation in experimental osteoarthritis and predict osteophyte progression in early human symptomatic osteoarthritis. Ann Rheum Dis 75(1):218\u2013225","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"762_CR53","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1002\/art.34315","volume":"64","author":"PL van Lent","year":"2012","unstructured":"van Lent PL, Blom AB, Schelbergen RF, Sloetjes A, Lafeber FP, Lems WF, Cats H, Vogl T, Roth J, van den Berg WB (2012) Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheum 64(5):1466\u20131476","journal-title":"Arthritis Rheum"},{"issue":"12","key":"762_CR54","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1136\/annrheumdis-2014-206517","volume":"74","author":"RF Schelbergen","year":"2015","unstructured":"Schelbergen RF, Geven EJ, van den Bosch MH, Eriksson H, Leanderson T, Vogl T, Roth J, van de Loo FA, Koenders MI, van der Kraan PM et al (2015) Prophylactic treatment with S100A9 inhibitor paquinimod reduces pathology in experimental collagenase-induced osteoarthritis. Ann Rheum Dis 74(12):2254\u20132258","journal-title":"Ann Rheum Dis"},{"issue":"8","key":"762_CR55","doi-asserted-by":"publisher","first-page":"5016","DOI":"10.4049\/jimmunol.174.8.5016","volume":"174","author":"R Liu-Bryan","year":"2005","unstructured":"Liu-Bryan R, Pritzker K, Firestein GS, Terkeltaub R (2005) TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. J Immunol 174(8):5016\u20135023","journal-title":"J Immunol"},{"issue":"10","key":"762_CR56","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.joca.2005.04.017","volume":"13","author":"SL Su","year":"2005","unstructured":"Su SL, Tsai CD, Lee CH, Salter DM, Lee HS (2005) Expression and regulation of Toll-like receptor 2 by IL-1beta and fibronectin fragments in human articular chondrocytes. Osteoarthr Cartil 13(10):879\u2013886","journal-title":"Osteoarthr Cartil"},{"issue":"7","key":"762_CR57","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1002\/art.21951","volume":"54","author":"HA Kim","year":"2006","unstructured":"Kim HA, Cho ML, Choi HY, Yoon CS, Jhun JY, Oh HJ, Kim HY (2006) The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis Rheum 54(7):2152\u20132163","journal-title":"Arthritis Rheum"},{"key":"762_CR58","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1186\/s13075-015-0833-9","volume":"17","author":"HS Hwang","year":"2015","unstructured":"Hwang HS, Park SJ, Cheon EJ, Lee MH, Kim HA (2015) Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes. Arthritis Res Ther 17:320","journal-title":"Arthritis Res Ther"},{"issue":"11","key":"762_CR59","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1136\/ard.2007.079574","volume":"67","author":"Q Zhang","year":"2008","unstructured":"Zhang Q, Hui W, Litherland GJ, Barter MJ, Davidson R, Darrah C, Donell ST, Clark IM, Cawston TE, Robinson JH, Rowan AD, Young DA (2008) Differential Toll-like receptor-dependent collagenase expression in chondrocytes. Ann Rheum Dis 67(11):1633\u20131641","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"762_CR60","doi-asserted-by":"publisher","first-page":"585","DOI":"10.3109\/17453674.2013.854666","volume":"84","author":"T Sillat","year":"2013","unstructured":"Sillat T, Barreto G, Clarijs P, Soininen A, Ainola M, Pajarinen J, Korhonen M, Konttinen YT, Sakalyte R, Hukkanen M, Ylinen P, Nordstr\u00f6m DCE (2013) Toll-like receptors in human chondrocytes and osteoarthritic cartilage. Acta Orthop 84(6):585\u2013592","journal-title":"Acta Orthop"},{"issue":"3","key":"762_CR61","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1080\/17453674.2017.1281058","volume":"88","author":"G Barreto","year":"2017","unstructured":"Barreto G, Sandelin J, Salem A, Nordstrom DC, Waris E (2017) Toll-like receptors and their soluble forms differ in the knee and thumb basal osteoarthritic joints. Acta Orthop 88(3):326\u2013333","journal-title":"Acta Orthop"},{"issue":"1","key":"762_CR62","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/jor.21494","volume":"30","author":"SL Su","year":"2012","unstructured":"Su SL, Yang HY, Lee CH, Huang GS, Salter DM, Lee HS (2012) The (-1486T\/C) promoter polymorphism of the TLR-9 gene is associated with end-stage knee osteoarthritis in a Chinese population. J Orthop Res 30(1):9\u201314","journal-title":"J Orthop Res"},{"issue":"11","key":"762_CR63","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1002\/jor.23559","volume":"35","author":"O Balbaloglu","year":"2017","unstructured":"Balbaloglu O, Sabah Ozcan S, Korkmaz M, Yilmaz N (2017) Promoter polymorphism (T-1486C) of TLR-9 gene is associated with knee osteoarthritis in a Turkish population. J Orthop Res 35(11):2484\u20132489","journal-title":"J Orthop Res"},{"issue":"5","key":"762_CR64","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1002\/jor.22291","volume":"31","author":"HY Yang","year":"2013","unstructured":"Yang HY, Lee HS, Lee CH, Fang WH, Chen HC, Salter DM, Su SL (2013) Association of a functional polymorphism in the promoter region of TLR-3 with osteoarthritis: a two-stage case-control study. J Orthop Res 31(5):680\u2013685","journal-title":"J Orthop Res"},{"issue":"11","key":"762_CR65","doi-asserted-by":"publisher","first-page":"e3165","DOI":"10.1038\/cddis.2017.534","volume":"8","author":"C Li","year":"2017","unstructured":"Li C, Chen K, Kang H, Yan Y, Liu K, Guo C, Qi J, Yang K, Wang F, Guo L, He C, Deng L (2017) Double-stranded RNA released from damaged articular chondrocytes promotes cartilage degeneration via Toll-like receptor 3-interleukin-33 pathway. Cell Death Dis 8(11):e3165","journal-title":"Cell Death Dis"},{"issue":"10","key":"762_CR66","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1016\/j.joca.2016.05.008","volume":"24","author":"ZY Huang","year":"2016","unstructured":"Huang ZY, Stabler T, Pei FX, Kraus VB (2016) Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthr Cartil 24(10):1769\u20131775","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"762_CR67","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nrrheum.2015.158","volume":"12","author":"Z Huang","year":"2016","unstructured":"Huang Z, Kraus VB (2016) Does lipopolysaccharide-mediated inflammation have a role in OA? Nat Rev Rheumatol 12(2):123\u2013129","journal-title":"Nat Rev Rheumatol"},{"issue":"4","key":"762_CR68","doi-asserted-by":"publisher","first-page":"e10079","DOI":"10.1002\/jbm4.10079","volume":"3","author":"E Kalaitzoglou","year":"2019","unstructured":"Kalaitzoglou E, Lopes EBP, Fu Y, Herron JC, Flaming JM, Donovan EL, Hu Y, Filiberti A, Griffin TM, Humphrey MB (2019) TLR4 promotes and DAP12 limits obesity-induced osteoarthritis in aged female mice. JBMR Plus 3(4):e10079","journal-title":"JBMR Plus"},{"issue":"1","key":"762_CR69","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.joca.2018.07.020","volume":"27","author":"JD Guss","year":"2019","unstructured":"Guss JD, Ziemian SN, Luna M, Sandoval TN, Holyoak DT, Guisado GG, Roubert S, Callahan RL, Brito IL, van der Meulen MCH, Goldring SR, Hernandez CJ (2019) The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis. Osteoarthr Cartil 27(1):129\u2013139","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"762_CR70","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.4049\/jimmunol.181.2.1446","volume":"181","author":"KL Lloyd-Jones","year":"2008","unstructured":"Lloyd-Jones KL, Kelly MM, Kubes P (2008) Varying importance of soluble and membrane CD14 in endothelial detection of lipopolysaccharide. J Immunol 181(2):1446\u20131453","journal-title":"J Immunol"},{"issue":"7","key":"762_CR71","doi-asserted-by":"publisher","first-page":"2268","DOI":"10.1002\/art.34495","volume":"64","author":"A Nair","year":"2012","unstructured":"Nair A, Kanda V, Bush-Joseph C, Verma N, Chubinskaya S, Mikecz K, Glant TT, Malfait AM, Crow MK, Spear GT, Finnegan A, Scanzello CR (2012) Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to toll-like receptor 4 and toll-like receptor 2 ligands via soluble CD14. Arthritis Rheum 64(7):2268\u20132277","journal-title":"Arthritis Rheum"},{"issue":"4","key":"762_CR72","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1002\/art.39006","volume":"67","author":"HN Daghestani","year":"2015","unstructured":"Daghestani HN, Pieper CF, Kraus VB (2015) Soluble macrophage biomarkers indicate inflammatory phenotypes in patients with knee osteoarthritis. Arthritis Rheumatol 67(4):956\u2013965","journal-title":"Arthritis Rheumatol"},{"issue":"12","key":"762_CR73","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1016\/j.joca.2018.08.005","volume":"26","author":"ZY Huang","year":"2018","unstructured":"Huang ZY, Perry E, Huebner JL, Katz B, Li YJ, Kraus VB (2018) Biomarkers of inflammation - LBP and TLR- predict progression of knee osteoarthritis in the DOXY clinical trial. Osteoarthr Cartil 26(12):1658\u20131665","journal-title":"Osteoarthr Cartil"},{"issue":"7","key":"762_CR74","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1002\/art.21122","volume":"52","author":"KD Brandt","year":"2005","unstructured":"Brandt KD, Mazzuca SA, Katz BP, Lane KA, Buckwalter KA, Yocum DE, Wolfe F, Schnitzer TJ, Moreland LW, Manzi S, Bradley JD, Sharma L, Oddis CV, Hugenberg ST, Heck LW (2005) Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum 52(7):2015\u20132025","journal-title":"Arthritis Rheum"},{"issue":"7","key":"762_CR75","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1074\/jbc.M115.675900","volume":"291","author":"E Krock","year":"2016","unstructured":"Krock E, Currie JB, Weber MH, Ouellet JA, Stone LS, Rosenzweig DH, Haglund L (2016) Nerve growth factor is regulated by Toll-like receptor 2 in human intervertebral discs. J Biol Chem 291(7):3541\u20133551","journal-title":"J Biol Chem"},{"issue":"5","key":"762_CR76","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.3390\/ijms18051028","volume":"18","author":"Gaetana Minnone","year":"2017","unstructured":"Minnone G, De Benedetti F, Bracci-Laudiero L (2017) NGF and its receptors in the regulation of inflammatory response. Int J Mol Sci 18(5)","journal-title":"International Journal of Molecular Sciences"},{"issue":"suppl_4","key":"762_CR77","doi-asserted-by":"publisher","first-page":"iv99","DOI":"10.1093\/rheumatology\/kex522","volume":"57","author":"RE Miller","year":"2018","unstructured":"Miller RE, Block JA, Malfait AM (2018) What is new in pain modification in osteoarthritis? Rheumatology (Oxford) 57(suppl_4):iv99\u2013iv107","journal-title":"Rheumatology (Oxford)"},{"issue":"12","key":"762_CR78","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1002\/eji.201444553","volume":"44","author":"M Baliu-Pique","year":"2014","unstructured":"Baliu-Pique M, Jusek G, Holzmann B (2014) Neuroimmunological communication via CGRP promotes the development of a regulatory phenotype in TLR4-stimulated macrophages. Eur J Immunol 44(12):3708\u20133716","journal-title":"Eur J Immunol"},{"key":"762_CR79","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3389\/fphys.2017.00508","volume":"8","author":"W Gao","year":"2017","unstructured":"Gao W, Xiong Y, Li Q, Yang H (2017) Inhibition of Toll-like receptor signaling as a promising therapy for inflammatory diseases: a journey from molecular to nano therapeutics. Front Physiol 8:508","journal-title":"Front Physiol"},{"issue":"2","key":"762_CR80","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1002\/cpt.522","volume":"101","author":"E Monnet","year":"2017","unstructured":"Monnet E, Lapeyre G, Poelgeest EV, Jacqmin P, Graaf K, Reijers J, Moerland M, Burggraaf J, Min C (2017) Evidence of NI-0101 pharmacological activity, an anti-TLR4 antibody, in a randomized phase I dose escalation study in healthy volunteers receiving LPS. Clin Pharmacol Ther 101(2):200\u2013208","journal-title":"Clin Pharmacol Ther"}],"container-title":["Seminars in Immunopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00281-019-00762-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00281-019-00762-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00281-019-00762-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T05:08:42Z","timestamp":1650085722000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00281-019-00762-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":80,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["762"],"URL":"https:\/\/doi.org\/10.1007\/s00281-019-00762-3","relation":{},"ISSN":["1863-2297","1863-2300"],"issn-type":[{"value":"1863-2297","type":"print"},{"value":"1863-2300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9]]},"assertion":[{"value":"8 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"R. E. Miller and C.R. Scanzello have no conflicts to declare. A.M. Malfait has received research funding from Galapagos N.V. and from GSK, and consulting fees from Eli-Lilly\/Pfizer, EMD Serono, and Vizuri.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}