CoChat
Sign Up
Cited by 1,302Osteoarthritis Treatment and MechanismsRheumatoid Arthritis Research and TherapiesMusculoskeletal synovial abnormalities and treatments

The role of synovitis in osteoarthritis pathogenesis

Open access
Scanzello, Carla R., Goldring, Steven R.·2012·Bone
DOI 10.1016/j.bone.2012.02.012PMC PMC3372675
Open this paper in CoChat — free account

Abstract

Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage and peri-articular bone, but there is increasing recognition that OA affects all of the joint tissues, including the synovium (SM). Under normal physiological conditions the synovial lining consists of a thin layer of cells with phenotypic features of macrophages and fibroblasts. These cells and the underlying vascularized connective tissue stroma form a complex structure that is an important source of synovial fluid (SF) components that are essential for normal cartilage and joint function. The histological changes observed in the SM in OA generally include features indicative of an inflammatory "synovitis"; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis. The pattern of synovial reaction varies with disease duration and associated metabolic and structural changes in other joint tissues. Imaging modalities including magnetic resonance (MRI) and ultrasound (US) have proved useful in detecting and quantifying synovial abnormalities, but individual studies have varied in their methods of evaluation. Despite these differences, most studies have concluded that the presence of synovitis in OA is associated with more severe pain and joint dysfunction. In addition, synovitis may be predictive of faster rates of cartilage loss in certain patient populations. Recent studies have provided insights into the pathogenic mechanisms underlying the development of synovitis in OA. Available evidence suggests that the inflammatory process involves engagement of Toll-like receptors and activation of the complement cascade by degradation products of extracellular matrices of cartilage and other joint tissues. The ensuing synovial reaction can lead to synthesis and release of a wide variety of cytokines and chemokines. Some of these inflammatory mediators are detected in joint tissues and SF in OA and have catabolic effects on chondrocytes. These inflammatory mediators represent potential targets for therapeutic interventions designed to reduce both symptoms and structural joint damage in OA. This article is part of a Special Issue entitled "Osteoarthritis".

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bone.2012.02.012

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Inflammatory cytokines play pivotal roles in the pathogenesis of degenerative joint disease, orchestrating catabolic processes that lead to progressive cartilage degradation, synovial inflammation, and bone remodeling.

    “Inflammatory cytokines play pivotal roles in the pathogenesis of degenerative joint disease, orchestrating catabolic processes that lead to progressive cartilage degradation, synovial inflammation, and bone remodeling [31,32,33].”

    From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [31]

    The Soluble Inflammatory Mediators section describes cytokines and chemokines that may contribute to joint inflammation and cartilage matrix destruction, and its IL-1 subsection describes catabolic effects on chondrocytes. The Conclusion says these mediators may affect cartilage homeostasis and peri-articular bone remodeling; it does not establish that cytokines orchestrate a progressive causal sequence across all three outcomes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 105

  1. [1]Abdollahi-Roodsaz S Joosten LA Koenders MI Devesa I Roelofs MF Radstake TR Heuvelmans-Jacobs M Akira S Nicklin MJ Ribeiro-Dias F van den Berg WB Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis J Clin Invest 2008 118 205 16 18060042 PMC2104479
  2. [3]Ayral X Pickering EH Woodworth TG Mackillop N Dougados M Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients Osteoarthritis Cartilage 2005 13 361 7 15882559
  3. [4]Baker K Grainger A Niu J Clancy M Guermazi A Crema M Hughes L Buckwalter J Wooley A Nevitt M Felson DT Relation of synovitis to knee pain using contrast-enhanced MRIs Ann Rheum Dis 2010 69 1779 83 20472593 PMC3885343
  4. [5]Barker SA Bayyuk SH Brimacombe JS Hawkins CF Stacey M Fingerprinting the Hyaluronic Acid Component of Normal and Pathological Synovial Fluids Clin Chim Acta 1963 8 902 9 14089562
  5. [6]Belcher C Yaqub R Fawthrop F Bayliss M Doherty M Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees Ann Rheum Dis 1997 56 299 307 9175930 PMC1752377
  6. [7]Benito MJ Veale DJ FitzGerald O van den Berg WB Bresnihan B Synovial tissue inflammation in early and late osteoarthritis Ann Rheum Dis 2005 64 1263 7 15731292 PMC1755629
  7. [8]Blom AB van Lent PL Libregts S Holthuysen AE van der Kraan PM van Rooijen N van den Berg WB Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3 Arthritis Rheum 2007 56 147 57 17195217
  8. [9]Bock HC Michaeli P Bode C Schultz W Kresse H Herken R Miosge N The small proteoglycans decorin and biglycan in human articular cartilage of late-stage osteoarthritis Osteoarthritis Cartilage 2001 9 654 63 11597178
  9. [10]Bondeson J Blom AB Wainwright S Hughes C Caterson B van den Berg WB The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis Arthritis Rheum 2010 62 647 57 20187160
  10. [11]Borzi RM Mazzetti I Cattini L Uguccioni M Baggiolini M Facchini A Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines Arthritis Rheum 2000 43 1734 41 10943863
  11. [12]Bradley K North J Saunders D Schwaeble W Jeziorska M Woolley DE Whaley K Synthesis of classical pathway complement components by chondrocytes Immunology 1996 88 648 56 8881771 PMC1456645
  12. [13]Bresnihan B Flanagan AM Firestein GS Budd RC Harris EDJ McInnes IB Ruddy S Sergent JS Synovium Kelley's Textbook of Rheumatology I 2009 23 36 Saunders Elsevier
  13. [14]Bruhl H Mack M Niedermeier M Lochbaum D Scholmerich J Straub RH Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes Rheumatology (Oxford) 2008 47 1771 4 18838387
  14. [15]Cantatore FP Benazzo F Ribatti D Lapadula G D'Amico S Tursi A Pipitone V Early alteration of synovial membrane in osteoarthrosis Clin Rheumatol 1988 7 214 9 3046827
  15. [16]Carrion M Juarranz Y Perez-Garcia S Jimeno R Pablos JL Gomariz RP Gutierrez-Canas I RNA sensors in human osteoarthritis and rheumatoid arthritis synovial fibroblasts: immune regulation by vasoactive intestinal peptide Arthritis Rheum 2011 63 1626 36 21337319
  16. [17]Chevalier X Claudepierre P Groult N Zardi L Hornebeck W Presence of ED-A containing fibronectin in human articular cartilage from patients with osteoarthritis and rheumatoid arthritis J Rheumatol 1996 23 1022 30 8782135
  17. [18]Chevalier X Giraudeau B Conrozier T Marliere J Kiefer P Goupille P Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study J Rheumatol 2005 32 1317 23 15996071
  18. [19]Chevalier X Groult N Larget-Piet B Zardi L Hornebeck W Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis Arthritis Rheum 1994 37 1013 22 7517675
  19. [20]Cohen SB Proudman S Kivitz AJ Burch FX Donohue JP Burstein D Sun YN Banfield C Vincent MS Ni L Zack DJ A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL 1R1) in patients with osteoarthritis of the knee Arthritis Res Ther 2011 13 R125 21801403 PMC3239365
  20. [21]Conaghan PG D'Agostino MA Le Bars M Baron G Schmidely N Wakefield R Ravaud P Grassi W Martin-Mola E So A Backhaus M Malaise M Emery P Dougados M Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study Ann Rheum Dis 2010 69 644 7 19433410
  21. [22]Crawford A Frazer A Lippitt JM Buttle DJ Smith T A case of chondromatosis indicates a synovial stem cell aetiology. Rheumatology (Oxford) 2006 45 1529 33 16670157
  22. [23]Cs-Szabo G Roughley PJ Plaas AH Glant TT Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage Arthritis Rheum 1995 38 660 8 7538297
  23. [24]Cuellar JM Scuderi GJ Cuellar VG Golish SR Yeomans DC Diagnostic utility of cytokine biomarkers in the evaluation of acute knee pain J Bone Joint Surg Am 2009 91 2313 20 19797564
  24. [25]Dahl LB Dahl IM Engstrom-Laurent A Granath K Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies Ann Rheum Dis 1985 44 817 22 4083937 PMC1001790
  25. [26]Dingle JT Saklatvala J Hembry R Tyler J Fell HB Jubb R A cartilage catabolic factor from synovium Biochem J 1979 184 177 80 534517 PMC1161690
  26. [28]Endres M Andreas K Kalwitz G Freymann U Neumann K Ringe J Sittinger M Haupl T Kaps C Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10 and XCL1 recruit human subchondral mesenchymal progenitor cells Osteoarthritis Cartilage 2010 18 1458 66 20709179
  27. [29]Fan J Varshney RR Ren L Cai D Wang DA Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration Tissue Eng Part B Rev 2009 15 75 86 19196118
  28. [30]Fernandez-Madrid F Karvonen RL Teitge RA Miller PR An T Negendank WG Synovial thickening detected by MR imaging in osteoarthritis of the knee confirmed by biopsy as synovitis Magn Reson Imaging 1995 13 177 83 7739358
  29. [31]Fotinos-Hoyer AK Guermazi A Jara H Eckstein F Ozonoff A Khard H Norbash A Bohndorf K Roemer FW Assessment of synovitis in the osteoarthritic knee: Comparison between manual segmentation, semiautomated segmentation, and semiquantitative assessment using contrast-enhanced fat-suppressed T1-weighted MRI Magn Reson Med 2010 64 604 9 20665803
  30. [32]Fox DB Warnock JJ Cell-based Meniscal Tissue Engineering: A Case for Synoviocytes Clin Orthop Relat Res 2011 PMC3171537 21360210
  31. [33]Fujikawa Y Shingu M Torisu T Masumi S Interleukin-1 receptor antagonist production in cultured synovial cells from patients with rheumatoid arthritis and osteoarthritis Ann Rheum Dis 1995 54 318 20 7763113 PMC1005582
  32. [34]Gobezie R Kho A Krastins B Sarracino DA Thornhill TS Chase M Millett PJ Lee DM High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis Arthritis Res Ther 2007 9 R36 17407561 PMC1906814
  33. [35]Goldberg RL Huff JP Lenz ME Glickman P Katz R Thonar EJ Elevated plasma levels of hyaluronate in patients with osteoarthritis and rheumatoid arthritis Arthritis Rheum 1991 34 799 807 2059228
  34. [36]Goldenberg DL Egan MS Cohen AS Inflammatory synovitis in degenerative joint disease J Rheumatol 1982 9 204 9 7097678
  35. [37]Goldring MB Birkhead J Sandell LJ Kimura T Krane SM Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes J Clin Invest 1988 82 2026 37 3264290 PMC442785
  36. [38]Goldring MB Otero M Plumb DA Dragomir C Favero M El Hachem K Hashimoto K Roach HI Olivotto E Borzi RM Marcu KB Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis Eur Cell Mater 2011 21 202 20 21351054 PMC3937960
  37. [39]Guermazi A Roemer FW Hayashi D Crema MD Niu J Zhang Y Marra MD Katur A Lynch JA El-Khoury GY Baker K Hughes LB Nevitt MC Felson DT Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study Ann Rheum Dis 2011 70 805 11 21187293 PMC4180232
  38. [40]Happonen KE Saxne T Aspberg A Morgelin M Heinegard D Blom AM Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis Arthritis Rheum 2010 62 3574 83 20737467 PMC4576017
  39. [41]Haringman JJ Smeets TJ Reinders-Blankert P Tak PP Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis Ann Rheum Dis 2006 65 294 300 16107514 PMC1798063
  40. [42]Heiland GR Aigner E Dallos T Sahinbegovic E Krenn V Thaler C Weiss G Distler JH Datz C Schett G Zwerina J Synovial immunopathology in haemochromatosis arthropathy Ann Rheum Dis 2010 69 1214 1219 19933745
  41. [43]Hill CL Hunter DJ Niu J Clancy M Guermazi A Genant H Gale D Grainger A Conaghan P Felson DT Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis Ann Rheum Dis 2007 66 1599 603 17491096 PMC2095318
  42. [44]Hui AY McCarty WJ Masuda K Firestein GS Sah RL A systems biology approach to synovial joint lubrication in health, injury, and disease Wiley Interdiscip Rev Syst Biol Med 2011 PMC3593048 21826801
  43. [45]Hunter DJ Lo GH Gale D Grainger AJ Guermazi A Conaghan PG The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score) Ann Rheum Dis 2008 67 206 11 17472995
  44. [46]Ishijima M Watari T Naito K Kaneko H Futami I Yoshimura-Ishida K Tomonaga A Yamaguchi H Yamamoto T Nagaoka I Kurosawa H Poole RA Kaneko K Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis Arthritis Res Ther 2011 13 R22 21320321 PMC3241366
  45. [48]Jin C Frayssinet P Pelker R Cwirka D Hu B Vignery A Eisenbarth SC Flavell RA NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy Proc Natl Acad Sci U S A 2011 PMC3169126 21856950
  46. [49]Jung YO Cho ML Kang CM Jhun JY Park JS Oh HJ Min JK Park SH Kim HY Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts Immunol Lett 2007 109 21 7 17289161
  47. [50]Kalchishkova N Furst CM Heinegard D Blom AM NC4 Domain of Cartilage-specific Collagen IX Inhibits Complement Directly Due to Attenuation of Membrane Attack Formation and Indirectly through Binding and Enhancing Activity of Complement Inhibitors C4B-binding Protein and Factor H J Biol Chem 2011 286 27915 26 21659506 PMC3151037
  48. [52]Kim HA Cho ML Choi HY Yoon CS Jhun JY Oh HJ Kim HY The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes Arthritis Rheum 2006 54 2152 63 16802353
  49. [53]Kokebie R Aggarwal R Lidder S Hakimiyan AA Rueger DC Block JA Chubinskaya S The role of synovial fluid markers of catabolism and anabolism in osteoarthritis, rheumatoid arthritis and asymptomatic organ donors Arthritis Res Ther 2011 13 R50 21435227 PMC3132039
  50. [54]Konttinen YT Ceponis A Meri S Vuorikoski A Kortekangas P Sorsa T Sukura A Santavirta S Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin (CD59) in synovial membrane Ann Rheum Dis 1996 55 888 94 9014582 PMC1010340
  51. [55]Krasnokutsky S Belitskaya-Levy I Bencardino J Samuels J Attur M Regatte R Rosenthal P Greenberg J Schweitzer M Abramson SB Rybak L Quantitative magnetic resonance imaging evidence of synovial proliferation is associated with radiographic severity of knee osteoarthritis Arthritis Rheum 2011 63 2983 91 21647860 PMC3183134
  52. [56]Krenn V Morawietz L Burmester GR Kinne RW Mueller-Ladner U Muller B Haupl T Synovitis score: discrimination between chronic low-grade and high-grade synovitis Histopathology 2006 49 358 64 16978198
  53. [57]Krenn V Morawietz L Haupl T Neidel J Petersen I Konig A Grading of chronic synovitis--a histopathological grading system for molecular and diagnostic pathology Pathol Res Pract 2002 198 317 25 12092767
  54. [58]Kyburz D Rethage J Seibl R Lauener R Gay RE Carson DA Gay S Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll-like receptor signaling Arthritis Rheum 2003 48 642 50 12632416
  55. [59]Lasarte JJ Casares N Gorraiz M Hervas-Stubbs S Arribillaga L Mansilla C Durantez M Llopiz D Sarobe P Borras-Cuesta F Prieto J Leclerc C The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo J Immunol 2007 178 748 56 17202335
  56. [60]Lawrence RC Felson DT Helmick CG Arnold LM Choi H Deyo RA Gabriel S Hirsch R Hochberg MC Hunder GG Jordan JM Katz JN Kremers HM Wolfe F Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II Arthritis Rheum 2008 58 26 35 18163497 PMC3266664
  57. [61]Lindblad S Hedfors E Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis Arthritis Rheum 1987 30 1081 8 3314876
  58. [62]Ling SM Patel DD Garnero P Zhan M Vaduganathan M Muller D Taub D Bathon JM Hochberg M Abernethy DR Metter EJ Ferrucci L Serum protein signatures detect early radiographic osteoarthritis Osteoarthritis Cartilage 2009 17 43 8 18571442 PMC2667202
  59. [63]Liu-Bryan R Terkeltaub R Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice Arthritis Rheum 2010 62 2004 12 20506365 PMC2902571
  60. [64]Liu L Ishijima M Futami I Kaneko H Kubota M Kawasaki T Matsumoto T Kurihara H Ning L Xu Z Ikeda H Takazawa Y Saita Y Kimura Y Xu S Kaneko K Kurosawa H 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 2010 29 1185 90 20567866
  61. [65]Loeuille D Chary-Valckenaere I Champigneulle J Rat AC Toussaint F Pinzano-Watrin A Goebel JC Mainard D Blum A Pourel J Netter P Gillet P Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity Arthritis Rheum 2005 52 3492 501 16255041
  62. [66]Long D Blake S Song XY Lark M Loeser RF Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13 Arthritis Res Ther 2008 10 R23 18289383 PMC2374453
  63. [67]Magnano MD Chakravarty EF Broudy C Chung L Kelman A Hillygus J Genovese M C. A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands J Rheumatol 2007 34 1323 7 17516620
  64. [68]Marcu KB Otero M Olivotto E Borzi RM Goldring MB NF-kappaB signaling: multiple angles to target OA Curr Drug Targets 2010 11 599 613 20199390 PMC3076145
  65. [70]Mazieres B Garnero P Gueguen A Abbal M Berdah L Lequesne M Nguyen M Salles JP Vignon E Dougados M Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort Ann Rheum Dis 2006 65 354 9 16322084 PMC1798072
  66. [71]Mengshol JA Vincenti MP Coon CI Barchowsky A Brinckerhoff CE Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3 Arthritis Rheum 2000 43 801 11 10765924
  67. [72]Midwood K Sacre S Piccinini AM Inglis J Trebaul A Chan E Drexler S Sofat N Kashiwagi M Orend G Brennan F Foxwell B Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease Nat Med 2009 15 774 80 19561617
  68. [73]Oehler S Neureiter D Meyer-Scholten C Aigner T Subtyping of osteoarthritic synoviopathy Clin Exp Rheumatol 2002 20 633 40 12412193
  69. [74]Ospelt C Brentano F Rengel Y Stanczyk J Kolling C Tak PP Gay RE Gay S Kyburz D Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis Arthritis Rheum 2008 58 3684 92 19035519
  70. [75]Ozawa T Koyama K Ando T Ohnuma Y Hatsushika K Ohba T Sugiyama H Hamada Y Ogawa H Okumura K Nakao A Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and interferon-gamma/dexamethasone Mod Rheumatol 2007 17 459 63 18084696
  71. [76]Pazar B Ea HK Narayan S Kolly L Bagnoud N Chobaz V Roger T Liote F So A Busso N Basic calcium phosphate crystals induce monocyte/macrophage IL-1beta secretion through the NLRP3 inflammasome in vitro J Immunol 2011 186 2495 502 21239716
  72. [77]Pessler F Dai L Diaz-Torne D Gomez-Vaquero C Paessler ME Zheng DH Einhorn E Range U Schumacher HR The synovitis of “non-inflammatory” orthopedic arthropathies: a quantitative histologic and immunohistochemical analysis Ann Rheum Dis 2008 18203762
  73. [78]Peterfy CG Guermazi A Zaim S Tirman PF Miaux Y White D Kothari M Lu Y Fye K Zhao S Genant HK Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis Osteoarthritis Cartilage 2004 12 177 90 14972335
  74. [79]Piccinini AM Midwood KS DAMPening inflammation by modulating TLR signalling Mediators Inflamm 2010 2010 PMC2913853 20706656
  75. [80]Poole AR Rosenberg LC Reiner A Ionescu M Bogoch E Roughley PJ Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage J Orthop Res 1996 14 681 9 8893759
  76. [81]Revell PA Mayston V Lalor P Mapp P The synovial membrane in osteoarthritis: a histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies Ann Rheum Dis 1988 47 300 7 3259125 PMC1003511
  77. [82]Rhee DK Marcelino J Baker M Gong Y Smits P Lefebvre V Jay GD Stewart M Wang H Warman ML Carpten JD The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth J Clin Invest 2005 115 622 31 15719068 PMC548698
  78. [83]Richardson DW Dodge GR Effects of interleukin-1beta and tumor necrosis factor-alpha on expression of matrix-related genes by cultured equine articular chondrocytes Am J Vet Res 2000 61 624 30 10850836
  79. [84]Roemer FW Guermazi A Felson DT Niu J Nevitt MC Crema MD Lynch JA Lewis CE Torner J Zhang Y Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study Ann Rheum Dis 2011 PMC3496084 21791448
  80. [85]Roemer FW Kassim Javaid M Guermazi A Thomas M Kiran A Keen R King L Arden NK Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI Osteoarthritis Cartilage 2010 18 1269 74 20691796
  81. [86]Rosenthal AK Gohr CM Ninomiya J Wakim BT Proteomic analysis of articular cartilage vesicles from normal and osteoarthritic cartilage Arthritis Rheum 2011 63 401 11 21279997 PMC3038242
  82. [87]Scanzello CR McKeon B Swaim BH DiCarlo E Asomugha EU Kanda V Nair A Lee DM Richmond JC Katz JN Crow MK Goldring SR Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship to symptoms Arthritis Rheum 2011 63 391 400 21279996 PMC3260472
  83. [88]Scanzello CR Plaas A Crow MK Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol 2008 20 565 72 18698179
  84. [89]Scanzello CR Umoh E Pessler F Diaz-Torne C Miles T Dicarlo E Potter HG Mandl L Marx R Rodeo S Goldring SR Crow MK Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease Osteoarthritis Cartilage 2009 17 1040 8 19289234
  85. [90]Schaefer L Babelova A Kiss E Hausser HJ Baliova M Krzyzankova M Marsche G Young MF Mihalik D Gotte M Malle E Schaefer RM Grone HJ The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages J Clin Invest 2005 115 2223 33 16025156 PMC1174916
  86. [91]Scheibner KA Lutz MA Boodoo S Fenton MJ Powell JD Horton MR Hyaluronan fragments act as an endogenous danger signal by engaging TLR2 J Immunol 2006 177 1272 81 16818787
  87. [92]Schlaak JF Pfers I Meyer Zum Buschenfelde KH Marker-Hermann E Different cytokine profiles in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and seronegative spondylarthropathies Clin Exp Rheumatol 1996 14 155 62 8737721
  88. [93]Sellam J Berenbaum F The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis Nat Rev Rheumatol 2010 6 625 35 20924410
  89. [94]Shen PC Wu CL Jou IM Lee CH Juan HY Lee PJ Chen SH Hsieh JL T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1gamma Osteoarthritis Cartilage 2011 19 728 36 21376128
  90. [95]Sjoberg A Onnerfjord P Morgelin M Heinegard D Blom AM The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q J Biol Chem 2005 280 32301 8 16046396
  91. [96]Sjoberg AP Manderson GA Morgelin M Day AJ Heinegard D Blom AM Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of complement interaction and activation Mol Immunol 2009 46 830 9 18962898 PMC2760063
  92. [97]Slansky E Li J Haupl T Morawietz L Krenn V Pessler F Quantitative determination of the diagnostic accuracy of the synovitis score and its components Histopathology 2010 57 436 43 20840673
  93. [98]Sohn DH Sokolove J Sharpe O Erhart JC Chandra PE Lahey LJ Lindstrom TM Hwang I Boyer KA Andriacchi TP Robinson WH Arthritis Res Ther 2012 14 1 R7 98 22225630 PMC3392793
  94. [99]Song IH Althoff CE Hermann KG Scheel AK Knetsch T Burmester GR Backhaus M Contrast-enhanced ultrasound in monitoring the efficacy of a bradykinin receptor 2 antagonist in painful knee osteoarthritis compared with MRI Ann Rheum Dis 2009 68 75 83 18375537
  95. [100]Sowers M Karvonen-Gutierrez CA Jacobson JA Jiang Y Yosef M Associations of anatomical measures from MRI with radiographically defined knee osteoarthritis score, pain, and physical functioning J Bone Joint Surg Am 2011 93 241 51 21266638 PMC3028452
  96. [101]Stafford CT Niedermeier W Holley HL Pigman W Studies on the Concentration and Intrinsic Viscosity of Hyaluronic Acid in Synovial Fluids of Patients with Rheumatic Diseases Ann Rheum Dis 1964 23 152 7 14130036 PMC1010360
  97. [102]Su SL Yang HY Lee CH Huang GS Salter DM Lee HS The (-1486T/C) promoter polymorphism of the TLR-9 gene is associated with end-stage knee osteoarthritis in a Chinese population J Orthop Res 2011 21748790
  98. [104]Tamaki Y Takakubo Y Hirayama T Konttinen YT Goodman SB Yamakawa M Takagi M Expression of Toll-like receptors and their signaling pathways in rheumatoid synovitis J Rheumatol 2011 38 810 20 21324962
  99. [105]Taylor KR Trowbridge JM Rudisill JA Termeer CC Simon JC Gallo RL Hyaluronan fragments stimulate endothelial recognition of injury through TLR4 J Biol Chem 2004 279 17079 84 14764599
  100. [107]Torres L Dunlop DD Peterfy C Guermazi A Prasad P Hayes KW Song J Cahue S Chang A Marshall M Sharma L The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis Osteoarthritis Cartilage 2006 14 1033 40 16713310
  101. [108]Tortorella MD Burn TC Pratta MA Abbaszade I Hollis JM Liu R Rosenfeld SA Copeland RA Decicco CP Wynn R Rockwell A Yang F Duke JL Solomon K George H Bruckner R Nagase H Itoh Y Ellis DM Ross H Wiswall BH Murphy K Hillman MC Jr. Hollis GF Newton RC Magolda RL Trzaskos JM Arner EC Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins Science 1999 284 1664 6 10356395
  102. [109]van Lent PL Blom AB van der Kraan P Holthuysen AE Vitters E van Rooijen N Smeets RL Nabbe KC van den Berg WB Crucial role of synovial lining macrophages in the promotion of transforming growth factor beta-mediated osteophyte formation Arthritis Rheum 2004 50 103 11 14730606
  103. [110]Walsh DA Bonnet CS Turner EL Wilson D Situ M McWilliams DF Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis Osteoarthritis Cartilage 2007 15 743 51 17376709
  104. [111]Wang Q Rozelle A Lepus C Scanzello C Song J Larsen D Crish J Bebek G Ritter S Lindstrom T Hwang I Wong H Punzi L Encarnacion A Shamloo M Goodman S Wyss-Coray T Goldring S Gobezie R Crow M Holers V Lee D Robinson W Identification of a central role for complement in osteoarthritis Nature Medicine 2011 17 1674 9 PMC3257059 22057346
  105. [112]Yang Z Schmitt JF Lee EH Immunohistochemical analysis of human mesenchymal stem cells differentiating into chondrogenic, osteogenic, and adipogenic lineages Methods Mol Biol 2011 698 353 66 21431531

Cited by

Sorted by citations

Authors
Scanzello, C. R., & Goldring, S. R.
Affiliations
  • Rush University Medical Center (US)
  • Hospital for Special Surgery (US)
Corresponding author
Scanzello, Carla R.
ORCID
Scanzello, Carla R.
Venue
Bone
Publisher
Elsevier BV
Published
2012-08
Volume
51
Issue
2
Pages
249-257
ISSN
  • 1873-2763 (ISSN-L)
  • 8756-3282
DOI
10.1016/j.bone.2012.02.012
PMC
PMC3372675
OpenAlex
W2085788584
Cited by
1,302
References
7
Citations by year
2026: 116 · 2025: 136 · 2024: 119 · 2023: 109 · 2022: 89 · 2021: 110 · 2020: 105 · 2019: 95 · 2018: 86 · 2017: 84 · 2016: 68 · 2015: 74 · 2014: 68 · 2013: 36 · 2012: 6
FWCI
8.82
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Bone (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5k08ar057859-05)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08-AR-057859, 1K08 AR057859-02)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Rheumatology › Musculoskeletal synovial abnormalities and treatments
Keywords
osteoarthritis, synovitis, synovium, synovial fluid, Toll-like receptors, complement system, cartilage degeneration, cytokines, chemokines, chondrocyte catabolism, synovial fibrosis, neoangiogenesis, joint pain
MeSH terms
Animals, Humans, Osteoarthritis, Synovial Membrane, Synovitis, Signal Transduction, Disease Progression, Inflammation Mediators

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review