{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:12:05Z","timestamp":1792807925156,"version":"4.5.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    It is now well recognized that osteoarthritis (OA) synovial membrane presents inflammatory components. The aim of this work is to provide evidence that similar inflammatory mechanisms exist in synovial membrane (n\u2009=\u200924) obtained from three pathologies presenting altogether an inflammatory gradient: OA, chronic pyrophosphate arthropathy (CPPA) and rheumatoid arthritis (RA). Synovial biopsies were first characterized by a histological score based on synovial hyperplasia and infiltration of lymphocytes, plasma cells, polymorphonuclear and macrophages. All biopsies were also analyzed by 2D-nano-UPLC-ESI-Q-Orbitrap for protein identification and quantification. Protein levels were correlated with the histological score. Histological score was in the range of 3 to 8 for OA, 5 to 13 for CPPA and 12 to 17 for RA. Of the 4,336 proteins identified by mass spectrometry, 51 proteins were selected for their strong correlation (p\u2009&lt;\u20090.001) with the histological score of which 11 proteins (\n                    <jats:italic>DNAJB11, CALR, ERP29, GANAB, HSP90B1, HSPA1A, HSPA5, HYOU1, LMAN1, PDIA4,<\/jats:italic>\n                    and\n                    <jats:italic>TXNDC5<\/jats:italic>\n                    ) were involved in the endoplasmic reticulum (ER) stress. Protein levels of S100A8 and S100A9 were significantly higher in RA compared to OA (for both) or to CPPA (for S100A8 only) and also significantly correlated with the histological score. Eighteen complement component proteins were identified, but only\n                    <jats:italic>C1QB<\/jats:italic>\n                    and\n                    <jats:italic>C1QBP<\/jats:italic>\n                    were weakly correlated with the histological score. This study highlights the inflammatory gradient existing between OA, CPPA and RA synovitis either at the protein level or at the histological level. Inflamed synovitis was characterized by the overexpression of ER stress proteins.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-70803-7","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T06:03:02Z","timestamp":1599199382000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Proteins involved in the endoplasmic reticulum stress are modulated in synovitis of osteoarthritis, chronic pyrophosphate arthropathy and rheumatoid arthritis, and correlate with the histological inflammatory score"],"prefix":"10.1038","volume":"10","author":[{"given":"Dominique","family":"de Seny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elettra","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Baiwir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Cobraiville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Collin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9gane","family":"Deli\u00e8ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jo\u00eblle","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Mazzucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Hauzeur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Delvenne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel G.","family":"Malaise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"70803_CR1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bone.2012.02.012","volume":"51","author":"CR Scanzello","year":"2012","unstructured":"Scanzello, C. R. & Goldring, S. R. The role of synovitis in osteoarthritis pathogenesis. Bone 51, 249\u2013257 (2012).","journal-title":"Bone"},{"key":"70803_CR2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","volume":"19","author":"A Mathiessen","year":"2017","unstructured":"Mathiessen, A. & Conaghan, P. G. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res. Ther. 19, 18 (2017).","journal-title":"Arthritis Res. Ther."},{"key":"70803_CR3","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.joca.2010.07.008","volume":"18","author":"FW Roemer","year":"2010","unstructured":"Roemer, F. W. et al. Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI. Osteoarthr. Cartil. 18, 1269\u20131274 (2010).","journal-title":"Osteoarthr. Cartil."},{"key":"70803_CR4","doi-asserted-by":"crossref","unstructured":"D\u2019Agostino, M. A. et al. EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: Prevalence of inflammation in osteoarthritis. Ann. Rheum. Dis. 64, 1703\u20131709 (2005).","DOI":"10.1136\/ard.2005.037994"},{"key":"70803_CR5","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s10067-010-1522-3","volume":"29","author":"L Liu","year":"2010","unstructured":"Liu, L. et al. Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery. Clin. Rheumatol. 29, 1185\u20131190 (2010).","journal-title":"Clin. Rheumatol."},{"key":"70803_CR6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrrheum.2014.209","volume":"11","author":"R G\u00f3mez","year":"2015","unstructured":"G\u00f3mez, R., Villalvilla, A., Largo, R., Gualillo, O. & Herrero-Beaumont, G. TLR4 signalling in osteoarthritis-finding targets for candidate DMOADs. Nat. Rev. Rheumatol. 11, 159\u2013170 (2015).","journal-title":"Nat. Rev. Rheumatol."},{"key":"70803_CR7","doi-asserted-by":"crossref","first-page":"e66769","DOI":"10.1371\/journal.pone.0066769","volume":"8","author":"D de Seny","year":"2013","unstructured":"de Seny, D. et al. Acute-phase serum amyloid a in osteoarthritis: Regulatory mechanism and proinflammatory properties. PLoS ONE 8, e66769 (2013).","journal-title":"PLoS ONE"},{"key":"70803_CR8","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1136\/ard.55.12.888","volume":"55","author":"YT Konttinen","year":"1996","unstructured":"Konttinen, Y. T. et al. Complement in acute and chronic arthritides: Assessment of C3c, C9, and protectin (CD59) in synovial membrane. Ann. Rheum. Dis. 55, 888\u2013894 (1996).","journal-title":"Ann. Rheum. Dis."},{"key":"70803_CR9","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/ar2172","volume":"9","author":"R Gobezie","year":"2007","unstructured":"Gobezie, R. et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res. Ther. 9, R36 (2007).","journal-title":"Arthritis Res. Ther."},{"key":"70803_CR10","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/art.37823","volume":"65","author":"SY Ritter","year":"2013","unstructured":"Ritter, S. Y. et al. Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis Rheum. 65, 981\u2013992 (2013).","journal-title":"Arthritis Rheum."},{"key":"70803_CR11","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1136\/ard.2010.135541","volume":"70","author":"D de Seny","year":"2011","unstructured":"de Seny, D. et al. Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis. Ann. Rheum. Dis. 70, 1144\u20131152 (2011).","journal-title":"Ann. Rheum. Dis."},{"key":"70803_CR12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12014-015-9091-8","volume":"12","author":"J Hayashi","year":"2015","unstructured":"Hayashi, J., Kihara, M., Kato, H. & Nishimura, T. A proteomic profile of synoviocyte lesions microdissected from formalin-fixed paraffin-embedded synovial tissues of rheumatoid arthritis. Clin. Proteomics 12, 20 (2015).","journal-title":"Clin. Proteomics"},{"key":"70803_CR13","doi-asserted-by":"crossref","first-page":"872","DOI":"10.3899\/jrheum.080939","volume":"36","author":"X Chang","year":"2009","unstructured":"Chang, X. et al. Identification of proteins with increased expression in rheumatoid arthritis synovial tissues. J. Rheumatol. 36, 872\u2013880 (2009).","journal-title":"J. Rheumatol."},{"key":"70803_CR14","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1006\/clin.1995.1149","volume":"77","author":"PP Tak","year":"1995","unstructured":"Tak, P. P. et al. Expression of adhesion molecules in early rheumatoid synovial tissue. Clin. Immunol. Immunopathol. 77, 236\u2013242 (1995).","journal-title":"Clin. Immunol. Immunopathol."},{"key":"70803_CR15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jbspin.2018.04.004","volume":"86","author":"A Najm","year":"2019","unstructured":"Najm, A. et al. IMSYC immunologic synovitis score: A new score for synovial membrane characterization in inflammatory and non-inflammatory arthritis. Jt. Bone Spine 86, 77\u201381 (2019).","journal-title":"Jt. Bone Spine"},{"key":"70803_CR16","doi-asserted-by":"crossref","first-page":"10665","DOI":"10.18632\/oncotarget.24366","volume":"9","author":"B Costanza","year":"2018","unstructured":"Costanza, B. et al. Innovative methodology for the identification of soluble biomarkers in fresh tissues. Oncotarget 9, 10665\u201310680 (2018).","journal-title":"Oncotarget"},{"key":"70803_CR17","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1074\/mcp.M113.031591","volume":"13","author":"J Cox","year":"2014","unstructured":"Cox, J. et al. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell. Proteomics 13, 2513\u20132526 (2014).","journal-title":"Mol. Cell. Proteomics"},{"key":"70803_CR18","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1136\/ard.16.4.494","volume":"16","author":"JH Kellgren","year":"1957","unstructured":"Kellgren, J. H. & Lawrence, J. S. Radiological assessment of osteo-arthrosis. Ann. Rheum. Dis. 16, 494\u2013502 (1957).","journal-title":"Ann. Rheum. Dis."},{"key":"70803_CR19","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.tips.2018.03.010","volume":"39","author":"M Rahmati","year":"2018","unstructured":"Rahmati, M., Moosavi, M. A. & McDermott, M. F. ER stress: A therapeutic target in rheumatoid arthritis? Trends Pharmacol. Sci. 39, 610\u2013623 (2018).","journal-title":"Trends Pharmacol. Sci."},{"key":"70803_CR20","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1084\/jem.20111783","volume":"209","author":"S-A Yoo","year":"2012","unstructured":"Yoo, S.-A. et al. A novel pathogenic role of the ER chaperone GRP78\/BiP in rheumatoid arthritis. J. Exp. Med. 209, 871\u2013886 (2012).","journal-title":"J. Exp. Med."},{"key":"70803_CR21","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1128\/MCB.00939-10","volume":"31","author":"S Nakajima","year":"2011","unstructured":"Nakajima, S. et al. Selective abrogation of BiP\/GRP78 blunts activation of NF-\u03baB through the ATF6 branch of the UPR: involvement of C\/EBP\u03b2 and mTOR-dependent dephosphorylation of Akt. Mol. Cell. Biol. 31, 1710\u20131718 (2011).","journal-title":"Mol. Cell. Biol."},{"key":"70803_CR22","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/gtc.12506","volume":"22","author":"T Fujimori","year":"2017","unstructured":"Fujimori, T. et al. Endoplasmic reticulum proteins SDF2 and SDF2L1 act as components of the BiP chaperone cycle to prevent protein aggregation. Genes Cells 22, 684\u2013698 (2017).","journal-title":"Genes Cells"},{"key":"70803_CR23","first-page":"1429","volume":"126","author":"F Guo","year":"2013","unstructured":"Guo, F. & Snapp, E. L. ERdj3 regulates BiP occupancy in living cells. J. Cell Sci. 126, 1429\u20131439 (2013).","journal-title":"J. Cell Sci."},{"key":"70803_CR24","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1182\/blood-2008-03-143107","volume":"112","author":"B Liu","year":"2008","unstructured":"Liu, B. & Li, Z. Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin. Blood 112, 1223\u20131230 (2008).","journal-title":"Blood"},{"key":"70803_CR25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2012.12.008","volume":"530","author":"Q-Q Huang","year":"2013","unstructured":"Huang, Q.-Q. & Pope, R. M. The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis. Arch. Biochem. Biophys. 530, 1\u20136 (2013).","journal-title":"Arch. Biochem. Biophys."},{"key":"70803_CR26","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.4049\/jimmunol.0801563","volume":"182","author":"Q-Q Huang","year":"2009","unstructured":"Huang, Q.-Q. et al. Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J. Immunol. 182, 4965\u20134973 (2009).","journal-title":"J. Immunol."},{"key":"70803_CR27","first-page":"841","volume":"36","author":"Y Jiao","year":"2018","unstructured":"Jiao, Y. et al. Bcl-XL and Mcl-1 upregulation by calreticulin promotes apoptosis resistance of fibroblast-like synoviocytes via activation of PI3K\/Akt and STAT3 pathways in rheumatoid arthritis. Clin. Exp. Rheumatol. 36, 841\u2013849 (2018).","journal-title":"Clin. Exp. Rheumatol."},{"key":"70803_CR28","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/cei.12411","volume":"178","author":"H Ding","year":"2014","unstructured":"Ding, H. et al. Calreticulin promotes angiogenesis via activating nitric oxide signalling pathway in rheumatoid arthritis. Clin. Exp. Immunol. 178, 236\u2013244 (2014).","journal-title":"Clin. Exp. Immunol."},{"key":"70803_CR29","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.3390\/ijms15022916","volume":"15","author":"C-C Duo","year":"2014","unstructured":"Duo, C.-C. et al. Soluble calreticulin induces tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin (IL)-6 production by macrophages through mitogen-activated protein kinase (MAPK) and NF\u03baB signaling pathways. Int. J. Mol. Sci. 15, 2916\u20132928 (2014).","journal-title":"Int. J. Mol. Sci."},{"key":"70803_CR30","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1091\/mbc.4.11.1109","volume":"4","author":"HY Lin","year":"1993","unstructured":"Lin, H. Y. et al. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Mol. Biol. Cell 4, 1109\u20131119 (1993).","journal-title":"Mol. Biol. Cell"},{"key":"70803_CR31","doi-asserted-by":"crossref","first-page":"6397","DOI":"10.1074\/jbc.274.10.6397","volume":"274","author":"K Ozawa","year":"1999","unstructured":"Ozawa, K. et al. 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death. J. Biol. Chem. 274, 6397\u20136404 (1999).","journal-title":"J. Biol. Chem."},{"key":"70803_CR32","first-page":"75","volume":"7","author":"D Zuo","year":"2016","unstructured":"Zuo, D., Subjeck, J. & Wang, X.-Y. Unfolding the role of large heat shock proteins: New insights and therapeutic implications. Front. Immunol. 7, 75 (2016).","journal-title":"Front. Immunol."},{"key":"70803_CR33","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.bbrc.2012.07.158","volume":"425","author":"K Tanaka","year":"2012","unstructured":"Tanaka, K. et al. Expression of 150-kDa oxygen-regulated protein (ORP150) stimulates bleomycin-induced pulmonary fibrosis and dysfunction in mice. Biochem. Biophys. Res. Commun. 425, 818\u2013824 (2012).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"70803_CR34","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/cei.13080","volume":"192","author":"J Li","year":"2018","unstructured":"Li, J. et al. TXNDC5 contributes to rheumatoid arthritis by down-regulating IGFBP1 expression. Clin. Exp. Immunol. 192, 82\u201394 (2018).","journal-title":"Clin. Exp. Immunol."},{"key":"70803_CR35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3899\/jrheum.170170","volume":"45","author":"B Xu","year":"2018","unstructured":"Xu, B. et al. CXCL10 and TRAIL are upregulated by TXNDC5 in rheumatoid arthritis fibroblast-like synoviocytes. J. Rheumatol. 45, 335\u2013340 (2018).","journal-title":"J. Rheumatol."},{"key":"70803_CR36","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/cmi.2017.20","volume":"15","author":"L Wang","year":"2018","unstructured":"Wang, L. et al. TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-\u03baB signaling. Cell. Mol. Immunol. 15, 685\u2013696 (2018).","journal-title":"Cell. Mol. Immunol."},{"key":"70803_CR37","doi-asserted-by":"crossref","first-page":"R124","DOI":"10.1186\/ar3429","volume":"13","author":"X Chang","year":"2011","unstructured":"Chang, X. et al. Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis. Arthritis Res. Ther. 13, R124 (2011).","journal-title":"Arthritis Res. Ther."},{"key":"70803_CR38","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/s12035-014-8840-4","volume":"52","author":"Y-H Zhang","year":"2015","unstructured":"Zhang, Y.-H. et al. Endoplasmic Reticulum Protein 29 Protects Axotomized Neurons from Apoptosis and Promotes Neuronal Regeneration Associated with Erk Signal. Mol. Neurobiol. 52, 522\u2013532 (2015).","journal-title":"Mol. Neurobiol."},{"key":"70803_CR39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.biocel.2010.09.019","volume":"43","author":"D Zhang","year":"2011","unstructured":"Zhang, D. & Richardson, D. R. Endoplasmic reticulum protein 29 (ERp29): An emerging role in cancer. Int. J. Biochem. Cell Biol. 43, 33\u201336 (2011).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"70803_CR40","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Solano, L., Reales-Calder\u00f3n, J. A., Nombela, C., Molero, G. & Gil, C. Proteomics of RAW 264.7 macrophages upon interaction with heat-inactivated Candida albicans cells unravel an anti-inflammatory response. Proteomics 9, 2995\u20133010 (2009).","DOI":"10.1002\/pmic.200800016"},{"key":"70803_CR41","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/cdd.2013.193","volume":"21","author":"G Tufo","year":"2014","unstructured":"Tufo, G. et al. The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma. Cell Death Differ. 21, 685\u2013695 (2014).","journal-title":"Cell Death Differ."},{"key":"70803_CR42","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.dld.2014.05.013","volume":"46","author":"A Negroni","year":"2014","unstructured":"Negroni, A. et al. Endoplasmic reticulum stress and unfolded protein response are involved in paediatric inflammatory bowel disease. Dig. Liver Dis. 46, 788\u2013794 (2014).","journal-title":"Dig. Liver Dis."},{"key":"70803_CR43","doi-asserted-by":"crossref","first-page":"25881","DOI":"10.1074\/jbc.M502160200","volume":"280","author":"B Zhang","year":"2005","unstructured":"Zhang, B., Kaufman, R. J. & Ginsburg, D. LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway. J. Biol. Chem. 280, 25881\u201325886 (2005).","journal-title":"J. Biol. Chem."},{"key":"70803_CR44","doi-asserted-by":"crossref","first-page":"31238","DOI":"10.1074\/jbc.M705558200","volume":"282","author":"TJ Nelson","year":"2007","unstructured":"Nelson, T. J. & Alkon, D. L. Protection against beta-amyloid-induced apoptosis by peptides interacting with beta-amyloid. J. Biol. Chem. 282, 31238\u201331249 (2007).","journal-title":"J. Biol. Chem."},{"key":"70803_CR45","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/glycob\/10.8.815","volume":"10","author":"MF Pelletier","year":"2000","unstructured":"Pelletier, M. F. et al. The heterodimeric structure of glucosidase II is required for its activity, solubility, and localization in vivo. Glycobiology 10, 815\u2013827 (2000).","journal-title":"Glycobiology"},{"key":"70803_CR46","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/s10753-010-9250-z","volume":"34","author":"X Luo","year":"2011","unstructured":"Luo, X., Zuo, X., Mo, X., Zhou, Y. & Xiao, X. Treatment with recombinant Hsp72 suppresses collagen-induced arthritis in mice. Inflammation 34, 432\u2013439 (2011).","journal-title":"Inflammation"},{"key":"70803_CR47","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1373\/clinchem.2007.099549","volume":"54","author":"D de Seny","year":"2008","unstructured":"de Seny, D. et al. Monomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis. Clin. Chem. 54, 1066\u20131075 (2008).","journal-title":"Clin. Chem."},{"key":"70803_CR48","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.revmed.2009.10.435","volume":"31","author":"A Baillet","year":"2010","unstructured":"Baillet, A. S100A8, S100A9 and S100A12 proteins in rheumatoid arthritis. La Rev. Med. interne 31, 458\u2013461 (2010).","journal-title":"La Rev. Med. interne"},{"key":"70803_CR49","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.3899\/jrheum.160270","volume":"43","author":"MH van den Bosch","year":"2016","unstructured":"van den Bosch, M. H. et al. Alarmin S100A9 induces proinflammatory and catabolic effects predominantly in the M1 macrophages of human osteoarthritic synovium. J. Rheumatol. 43, 1874\u20131884 (2016).","journal-title":"J. Rheumatol."},{"key":"70803_CR50","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1002\/art.34315","volume":"64","author":"PLEM van Lent","year":"2012","unstructured":"van Lent, P. L. E. M. et al. Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheum. 64, 1466\u20131476 (2012).","journal-title":"Arthritis Rheum."},{"key":"70803_CR51","doi-asserted-by":"crossref","unstructured":"Lambert, C. et al. Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol. (Hoboken, N.J.) 66, 960\u20138 (2014).","DOI":"10.1002\/art.38315"},{"key":"70803_CR52","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/art.10183","volume":"46","author":"E Neumann","year":"2002","unstructured":"Neumann, E. et al. Local production of complement proteins in rheumatoid arthritis synovium. Arthritis Rheum. 46, 934\u2013945 (2002).","journal-title":"Arthritis Rheum."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70803-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70803-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70803-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T13:18:05Z","timestamp":1670332685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70803-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["70803"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-70803-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]},"assertion":[{"value":"17 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14159"}}