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.
Adult
Aged
Aged, 80 and over
Arthritis, Rheumatoid
/ immunology
Biomarkers
/ analysis
Chondrocalcinosis
/ immunology
Diphosphates
/ metabolism
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress
Female
Humans
Inflammation
/ immunology
Inflammation Mediators
/ metabolism
Male
Middle Aged
Osteoarthritis
/ immunology
Proteins
/ analysis
Proteome
/ analysis
Retrospective Studies
Synovitis
/ immunology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
received:
17
04
2020
accepted:
03
08
2020
entrez:
5
9
2020
pubmed:
6
9
2020
medline:
13
1
2021
Statut:
epublish
Résumé
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 = 24) 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 < 0.001) with the histological score of which 11 proteins (DNAJB11, CALR, ERP29, GANAB, HSP90B1, HSPA1A, HSPA5, HYOU1, LMAN1, PDIA4, and TXNDC5) 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 C1QB and C1QBP 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.
Identifiants
pubmed: 32887899
doi: 10.1038/s41598-020-70803-7
pii: 10.1038/s41598-020-70803-7
pmc: PMC7473860
doi:
Substances chimiques
Biomarkers
0
Diphosphates
0
Endoplasmic Reticulum Chaperone BiP
0
HSPA5 protein, human
0
Inflammation Mediators
0
Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14159Références
Scanzello, C. R. & Goldring, S. R. The role of synovitis in osteoarthritis pathogenesis. Bone 51, 249–257 (2012).
pubmed: 22387238
pmcid: 3372675
Mathiessen, A. & Conaghan, P. G. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res. Ther. 19, 18 (2017).
pubmed: 28148295
pmcid: 5289060
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, 1269–1274 (2010).
pubmed: 20691796
D’Agostino, 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, 1703–1709 (2005).
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, 1185–1190 (2010).
pubmed: 20567866
Gómez, R., Villalvilla, A., Largo, R., Gualillo, O. & Herrero-Beaumont, G. TLR4 signalling in osteoarthritis-finding targets for candidate DMOADs. Nat. Rev. Rheumatol. 11, 159–170 (2015).
pubmed: 25512010
de Seny, D. et al. Acute-phase serum amyloid a in osteoarthritis: Regulatory mechanism and proinflammatory properties. PLoS ONE 8, e66769 (2013).
pubmed: 23776697
pmcid: 3680431
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, 888–894 (1996).
pubmed: 9014582
pmcid: 1010340
Gobezie, R. et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res. Ther. 9, R36 (2007).
pubmed: 17407561
pmcid: 1906814
Ritter, S. Y. et al. Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis Rheum. 65, 981–992 (2013).
pubmed: 23400684
pmcid: 3618606
de Seny, D. et al. Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis. Ann. Rheum. Dis. 70, 1144–1152 (2011).
pubmed: 21362709
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).
pubmed: 26251654
pmcid: 4527102
Chang, X. et al. Identification of proteins with increased expression in rheumatoid arthritis synovial tissues. J. Rheumatol. 36, 872–880 (2009).
pubmed: 19369474
Tak, P. P. et al. Expression of adhesion molecules in early rheumatoid synovial tissue. Clin. Immunol. Immunopathol. 77, 236–242 (1995).
pubmed: 7586733
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, 77–81 (2019).
Costanza, B. et al. Innovative methodology for the identification of soluble biomarkers in fresh tissues. Oncotarget 9, 10665–10680 (2018).
pubmed: 29535834
pmcid: 5828218
Cox, J. et al. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell. Proteomics 13, 2513–2526 (2014).
pubmed: 24942700
pmcid: 4159666
Kellgren, J. H. & Lawrence, J. S. Radiological assessment of osteo-arthrosis. Ann. Rheum. Dis. 16, 494–502 (1957).
pubmed: 13498604
pmcid: 1006995
Rahmati, M., Moosavi, M. A. & McDermott, M. F. ER stress: A therapeutic target in rheumatoid arthritis? Trends Pharmacol. Sci. 39, 610–623 (2018).
pubmed: 29691058
Yoo, S.-A. et al. A novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis. J. Exp. Med. 209, 871–886 (2012).
pubmed: 22430489
pmcid: 3328363
Nakajima, S. et al. Selective abrogation of BiP/GRP78 blunts activation of NF-κB through the ATF6 branch of the UPR: involvement of C/EBPβ and mTOR-dependent dephosphorylation of Akt. Mol. Cell. Biol. 31, 1710–1718 (2011).
pubmed: 21300786
pmcid: 3126329
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, 684–698 (2017).
pubmed: 28597544
Guo, F. & Snapp, E. L. ERdj3 regulates BiP occupancy in living cells. J. Cell Sci. 126, 1429–1439 (2013).
pubmed: 23378021
pmcid: 3644143
Liu, B. & Li, Z. Endoplasmic reticulum HSP90b1 (gp96, grp94) optimizes B-cell function via chaperoning integrin and TLR but not immunoglobulin. Blood 112, 1223–1230 (2008).
pubmed: 18509083
pmcid: 2515121
Huang, Q.-Q. & Pope, R. M. The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis. Arch. Biochem. Biophys. 530, 1–6 (2013).
pubmed: 23257071
Huang, Q.-Q. et al. Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J. Immunol. 182, 4965–4973 (2009).
pubmed: 19342676
pmcid: 2814438
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, 841–849 (2018).
pubmed: 29652658
Ding, H. et al. Calreticulin promotes angiogenesis via activating nitric oxide signalling pathway in rheumatoid arthritis. Clin. Exp. Immunol. 178, 236–244 (2014).
pubmed: 24988887
pmcid: 4233373
Duo, C.-C. et al. Soluble calreticulin induces tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 production by macrophages through mitogen-activated protein kinase (MAPK) and NFκB signaling pathways. Int. J. Mol. Sci. 15, 2916–2928 (2014).
pubmed: 24566135
pmcid: 3958890
Lin, H. Y. et al. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Mol. Biol. Cell 4, 1109–1119 (1993).
pubmed: 8305733
pmcid: 275747
Ozawa, K. et al. 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death. J. Biol. Chem. 274, 6397–6404 (1999).
pubmed: 10037731
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).
pubmed: 26973652
pmcid: 4771732
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, 818–824 (2012).
pubmed: 22892132
Li, J. et al. TXNDC5 contributes to rheumatoid arthritis by down-regulating IGFBP1 expression. Clin. Exp. Immunol. 192, 82–94 (2018).
pubmed: 29131315
Xu, B. et al. CXCL10 and TRAIL are upregulated by TXNDC5 in rheumatoid arthritis fibroblast-like synoviocytes. J. Rheumatol. 45, 335–340 (2018).
pubmed: 29247155
Wang, L. et al. TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling. Cell. Mol. Immunol. 15, 685–696 (2018).
pubmed: 28603283
Chang, X. et al. Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis. Arthritis Res. Ther. 13, R124 (2011).
pubmed: 21801346
pmcid: 3239364
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, 522–532 (2015).
pubmed: 25204493
Zhang, D. & Richardson, D. R. Endoplasmic reticulum protein 29 (ERp29): An emerging role in cancer. Int. J. Biochem. Cell Biol. 43, 33–36 (2011).
pubmed: 20920593
Martínez-Solano, L., Reales-Calderón, 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, 2995–3010 (2009).
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, 685–695 (2014).
pubmed: 24464223
pmcid: 3978299
Negroni, A. et al. Endoplasmic reticulum stress and unfolded protein response are involved in paediatric inflammatory bowel disease. Dig. Liver Dis. 46, 788–794 (2014).
pubmed: 24953208
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, 25881–25886 (2005).
pubmed: 15886209
Nelson, T. J. & Alkon, D. L. Protection against beta-amyloid-induced apoptosis by peptides interacting with beta-amyloid. J. Biol. Chem. 282, 31238–31249 (2007).
pubmed: 17761669
Pelletier, M. F. et al. The heterodimeric structure of glucosidase II is required for its activity, solubility, and localization in vivo. Glycobiology 10, 815–827 (2000).
pubmed: 10929008
Luo, X., Zuo, X., Mo, X., Zhou, Y. & Xiao, X. Treatment with recombinant Hsp72 suppresses collagen-induced arthritis in mice. Inflammation 34, 432–439 (2011).
pubmed: 20852924
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, 1066–1075 (2008).
pubmed: 18436720
Baillet, A. S100A8, S100A9 and S100A12 proteins in rheumatoid arthritis. La Rev. Med. interne 31, 458–461 (2010).
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, 1874–1884 (2016).
pubmed: 27481901
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, 1466–1476 (2012).
pubmed: 22143922
Lambert, C. et al. Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol. (Hoboken, N.J.) 66, 960–8 (2014).
Neumann, E. et al. Local production of complement proteins in rheumatoid arthritis synovium. Arthritis Rheum. 46, 934–945 (2002).
pubmed: 11953970