CoChat
Sign Up
Cited by 64Osteoarthritis Treatment and MechanismsRheumatoid Arthritis Research and TherapiesEstrogen and related hormone effects

Arthritis and the role of endogenous glucocorticoids

Open access
Macfarlane, Eugenie, Seibel, Markus J., Zhou, Hong·2020·Bone Research
DOI 10.1038/s41413-020-00112-2PMC PMC7478967
Open this paper in CoChat — free accountOpen PDF

Abstract

Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

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 · 10.1038/s41413-020-00112-2

Cites

15 of 15 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?

  • Impaired HPA-axis reactivity diminishes anti-inflammatory cortisol secretion and alters glucocorticoid receptor sensitivity, weakening feedback loops between the hypothalamus and pituitary.

    “impaired HPA-axis reactivity diminishes anti-inflammatory cortisol secretion and alters glucocorticoid receptor sensitivity, weakening the feedback loops between the hypothalamus and pituitary [77,78]”

    From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [78]

    The ‘Endogenous glucocorticoid actions in rheumatoid arthritis’ section (page unavailable) reports a reduced cortisol response to stimulation and a failure to increase glucocorticoids during chronic inflammation. It does not establish that impaired reactivity alters receptor sensitivity or weakens hypothalamic–pituitary feedback: its arthritis mouse-model passage instead proposes enhanced pituitary negative feedback. Reduced hypothalamic receptor expression is discussed separately in the context of aging. (LLM, conf=0.87)

    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: 253

  1. [1]James SL Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 Lancet 2018 392 1789 1858 30496104 PMC6227754
  2. [2]March LM Bachmeier CJM 10 Economics of osteoarthritis: a global perspective Baillière’s Clin. Rheumatol. 1997 11 817 834 9429738
  3. [3]Murphy LB Cisternas MG Pasta DJ Helmick CG Yelin EH Medical expenditures and earnings losses among US adults with arthritis in 2013 Arthritis Care Res. 2018 70 869 876 28950426
  4. [4]Aletaha D 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative Arthritis Rheumatol. 2010 62 2569 2581 20872595
  5. [5]Cross M The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 Study Ann. Rheum. Dis. 2014 73 1323 1330 24553908
  6. [6]The Joint Committee of the Medical Research Council and Nuffield Foundation. A comparison of cortisone and aspirin in the treatment of early cases of rheumatoid arthritis; a report by the Joint Committee of the Medical Research Council and Nuffield Foundation on clinical trials of cortisone, A.C.T.H., and other therapeutic measures in chronic rheumatic diseases BMJ 1954 1 1223 1227 13160439 PMC2085095
  7. [7]Hench PS The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis Proc. Staff Meet. Mayo Clin. 1949 24 181 197 18118071
  8. [8]The Joint Committee of the Medical Research Council and Nuffield Foundation. A comparison of prednisolone with aspirin or other analgesics in the treatment of rheumatoid arthritis. A second report by the joint committee of the Medical Research Council and Nuffield Foundation on clinical trials of cortisone, ACTH, and other therapeutic measures in chronic rheumatic diseases Ann. Rheum. Dis. 1960 19 331 337 14447267 PMC1007163
  9. [9]Saag KG Criswell LA Sems KM Nettleman MD Kolluri S Low-dose corticosteroids in rheumatoid arthritis. A meta-analysis of their moderate-term effectiveness Arthritis Rheum. 1996 39 1818 1825 8912503
  10. [10]McDonough AK Curtis JR Saag KG The epidemiology of glucocorticoid-associated adverse events Curr. Opin. Rheumatol. 2008 20 131 137 18349741
  11. [11]McAlindon TE Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial JAMA 2017 317 1967 1975 28510679 PMC5815012
  12. [12]Wernecke C Braun HJ Dragoo JL The effect of intra-articular corticosteroids on articular cartilage: a systematic review Orthop. J. Sports Med. 2015 3 2325967115581163 26674652 PMC4622344
  13. [13]Taurog JD Chhabra A Colbert RA Ankylosing spondylitis and axial spondyloarthritis N. Engl J. Med. 2016 374 2563 2574 27355535
  14. [14]Ritchlin CT Colbert RA Gladman DD Psoriatic arthritis N. Engl J. Med. 2017 376 957 970 28273019
  15. [16]Roddy E Zhang W Doherty M The changing epidemiology of gout Nat. Clin. Pract. Rheumatol. 2007 3 443 449 17664951
  16. [17]Emery P Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide Ann. Rheum. Dis. 2002 61 290 297 11874828 PMC1754044
  17. [18]Grassi W De Angelis R Lamanna G Cervini C The clinical features of rheumatoid arthritis Eur. J. Radiol. 1998 27 S18 S24 9652497
  18. [19]Finckh A Liang MH van Herckenrode CM de Pablo P Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: a meta-analysis Arthritis Rheum. 2006 55 864 872 17139662
  19. [20]Goekoop-Ruiterman YPM Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial Ann. Intern. Med. 2007 146 406 415 17371885
  20. [21]Singh JA 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis Arthritis Rheumatol. 2016 68 1 26 26545940
  21. [22]Smolen JS EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update Ann. Rheum. Dis. 2017 76 960 977 28264816
  22. [23]Catrina AI Ytterberg AJ Reynisdottir G Malmström V Klareskog L Lungs, joints and immunity against citrullinated proteins in rheumatoid arthritis Nat. Rev. Rheumatol. 2014 10 645 653 25072264
  23. [24]van Zanten A Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands Ann. Rheum. Dis. 2017 76 1184 1190 28043998 PMC5530344
  24. [25]Syversen SW High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study Ann. Rheum. Dis. 2008 67 212 217 17526555
  25. [26]Clavel C Induction of macrophage secretion of tumor necrosis factor α through Fcγ receptor IIa engagement by rheumatoid arthritis-specific autoantibodies to citrullinated proteins complexed with fibrinogen Arthritis Rheum. 2008 58 678 688 18311806
  26. [27]Harre U Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin J. Clin. Investig. 2012 122 1791 1802 22505457 PMC3336988
  27. [28]Engdahl C Periarticular bone loss in arthritis is induced by autoantibodies against citrullinated vimentin J. Bone Miner. Res. 2017 32 1681 1691 28425620
  28. [29]MacGregor AJ Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins Arthritis Rheum. 2000 43 30 37 10643697
  29. [30]Saag KG Cigarette smoking and rheumatoid arthritis severity Ann. Rheum. Dis. 1997 56 463 469 9306868 PMC1752420
  30. [31]Másdóttir B Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis Rheumatology 2000 39 1202 1205 11085797
  31. [32]Scher JU Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis Arthritis Rheum. 2012 64 3083 3094 22576262 PMC3428472
  32. [33]Scher JU Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis eLife 2013 2 e01202 24192039 PMC3816614
  33. [34]Pianta A Evidence of the immune relevance of Prevotella copri, a gut microbe, in patients with rheumatoid arthritis Arthritis Rheumatol. 2017 69 964 975 27863183 PMC5406252
  34. [35]Stastny P Association of the b-cell alloantigen DRw4 with rheumatoid arthritis N. Engl J. Med. 1978 298 869 871 147420
  35. [36]Gregersen PK Silver J Winchester RJ The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis Arthritis Rheum. 1987 30 1205 1213 2446635
  36. [37]Weyand CM Hicok KC Conn DL Goronzy JJ The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis Ann. Intern. Med. 1992 117 801 806 1416553
  37. [38]Huizinga TW Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins Arthritis Rheum. 2005 52 3433 3438 16255021
  38. [39]Padyukov L A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis Ann. Rheum. Dis. 2011 70 259 265 21156761 PMC3015094
  39. [40]Derijk RH A human glucocorticoid receptor gene variant that increases the stability of the glucocorticoid receptor beta-isoform mRNA is associated with rheumatoid arthritis J. Rheumatol. 2001 28 2383 2388 11708406
  40. [41]de Hair MJH Features of the synovium of individuals at risk of developing rheumatoid arthritis: implications for understanding preclinical rheumatoid arthritis Arthritis Rheumatol. 2014 66 513 522 24574210 PMC4034588
  41. [42]Shiozawa S Shiozawa K Fujita T Morphologic observations in the early phase of the cartilage-pannus junction Arthritis Rheum. 1983 26 472 478 6838672
  42. [43]Bromley M Woolley DE Histopathology of the rheumatoid lesion Arthritis Rheum. 1984 27 857 863 6466394
  43. [44]Fassbender HG The role of connective tissue cells in the synovial tissue Rheumatol. Rehabil. 1979 18 5 7 441632
  44. [45]Fassbender HG Simmling-Annefeld M The potential aggressiveness of synovial tissue in rheumatoid arthritis J. Pathol. 1983 139 399 406 6834180
  45. [46]Fassbender HG Histomorphological basis of articular cartilage destruction in rheumatoid arthritis Coll. Relat. Res. 1983 3 141 155 6851475
  46. [47]Fassbender HG Is pannus a residue of inflammation? Arthritis Rheum. 1984 27 956 957 6466399
  47. [48]Fassbender HG Seibel M Hebert T Pathways of destruction in metacarpal and metatarsal joints of patients with rheumatoid arthritis Scand. J. Rheumatol. 1992 21 10 16 1570480
  48. [49]Elshabrawy HA The pathogenic role of angiogenesis in rheumatoid arthritis Angiogenesis 2015 18 433 448 26198292 PMC4879881
  49. [50]Lafyatis R Anchorage-independent growth of synoviocytes from arthritic and normal joints. Stimulation by exogenous platelet-derived growth factor and inhibition by transforming growth factor-beta and retinoids J. Clin. Investig. 1989 83 1267 1276 2784799 PMC303817
  50. [51]Rinaldi N Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins Ann. Rheum. Dis. 1997 56 45 51 9059141 PMC1752256
  51. [52]Lefèvre S Synovial fibroblasts spread rheumatoid arthritis to unaffected joints Nat. Med. 2009 15 1414 1420 19898488 PMC3678354
  52. [53]Tak PP Bresnihan B The pathogenesis and prevention of joint damage in rheumatoid arthritis: advances from synovial biopsy and tissue analysis Arthritis Rheum. 2000 43 2619 2633 11145019
  53. [54]Kennedy A Fearon U Veale D Godson C Macrophages in synovial inflammation Front Immunol. 2011 2 52 22566842 PMC3342259
  54. [55]Fukui S M1 and M2 monocytes in rheumatoid arthritis: a contribution of imbalance of M1/M2 monocytes to osteoclastogenesis Front Immunol. 2018 8 1958 29375576 PMC5766997
  55. [56]Stockinger B Veldhoen M Differentiation and function of Th17 T cells Curr. Opin. Immunol. 2007 19 281 286 17433650
  56. [57]Ziolkowska M High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin a-sensitive mechanism J. Immunol. 2000 164 2832 2838 10679127
  57. [58]Nakae S Nambu A Sudo K Iwakura Y Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice J. Immunol. 2003 171 6173 6177 14634133
  58. [59]Pfeifle R Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease Nat. Immunol. 2017 18 104 113 27820809 PMC5164937
  59. [60]Kobayashi I Ziff M Electron microscopic studies of the cartilage-pannus junction in rheumatoid arthritis Arthritis Rheum. 1975 18 475 483 1191348
  60. [61]Ainola M Pannus invasion and cartilage degradation in rheumatoid arthritis: involvement of MMP-3 and interleukin-1b Clin. Exp. Rheumatol. 2005 23 644 650 16173240
  61. [62]Hembry RM Bagga MR Reynolds JJ Hamblen DL Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo- and rheumatoid arthritis Ann. Rheum. Dis. 1995 54 25 32 7880117 PMC1005508
  62. [63]Mimata Y Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis Int J. Rheum. Dis. 2012 15 36 44 22324945
  63. [64]Vankemmelbeke MN Expression and activity of ADAMTS-5 in synovium Eur. J. Biochem. 2001 268 1259 1268 11231277
  64. [65]Hou W-S Cathepsin K is a critical protease in synovial fibroblast-mediated collagen degradation Am. J. Pathol. 2001 159 2167 2177 11733367 PMC1850593
  65. [66]Chabaud M Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis Cytokine 2000 12 1092 1099 10880256
  66. [67]Mitchell NS Shepard N Changes in proteoglycan and collagen in cartilage in rheumatoid arthritis J. Bone Jt. Surg. Am. 1978 60 342 348 77275
  67. [68]Korb-Pap A Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis Ann. Rheum. Dis. 2012 71 1004 1011 22258493
  68. [69]Mazzetti I Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis Clin. Sci. 2001 101 593 539 11724645
  69. [70]Aida Y The effect of IL-1β on the expression of inflammatory cytokines and their receptors in human chondrocytes Life Sci. 2006 79 764 771 16616208
  70. [71]Pap T Modulation of fibroblast-mediated cartilage degradation by articular chondrocytes in rheumatoid arthritis Arthritis Rheum. 2000 43 2531 2536 11083277
  71. [72]Yatsugi N Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc J. Orthop. Sci. 2000 5 150 156 10982649
  72. [73]Machold KP Very recent onset arthritis-clinical, laboratory, and radiological findings during the first year of disease J. Rheumatol. 2002 29 2278 2287 12415582
  73. [74]van der Heijde DM Joint erosions and patients with early rheumatoid arthritis Rheumatology 1995 34 74 78 8535653
  74. [75]Ødegård S Association of early radiographic damage with impaired physical function in rheumatoid arthritis: a ten-year, longitudinal observational study in 238 patients Arthritis Rheum. 2006 54 68 75 16385497
  75. [76]McGonagle D Tan AL Moller Dohn U Ostergaard M Benjamin M Microanatomic studies to define predictive factors for the topography of periarticular erosion formation in inflammatory arthritis Arthritis Rheum. 2009 60 1042 1051 19333927
  76. [77]Cambré I Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis Nat. Commun. 2018 9 4613 4613 30397205 PMC6218475
  77. [78]Gravallese EM Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor Arthritis Rheum. 2000 43 250 258 10693863
  78. [79]Bromley M Woolley DE Chondroclasts and osteoclasts at subchondral sites of erosion in the rheumatoid joint Arthritis Rheum. 1984 27 968 975 6236824
  79. [80]Pettit AR Walsh NC Manning C Goldring SR Gravallese EM RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis Rheumatology 2006 45 1068 1076 16490750
  80. [81]Romas E Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis Am. J. Pathol. 2002 161 1419 1427 12368214 PMC1867274
  81. [83]Kleyer A Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies Ann. Rheum. Dis. 2014 73 854 860 23520034
  82. [84]Oray M Abu Samra K Ebrahimiadib N Meese H Foster CS Long-term side effects of glucocorticoids Expert Opin. Drug Saf. 2016 15 457 465 26789102
  83. [85]Hardy RS Zhou H Seibel MJ Cooper MS Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy Endocr. Rev. 2018 39 519 548 29905835
  84. [87]Hoes JN EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases Ann. Rheum. Dis. 2007 66 1560 1567 17660219 PMC2095301
  85. [88]Ho CTK Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology Clin. Rheumatol. 2019 38 3331 3350 31485846
  86. [89]Makrygiannakis D Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis Arthritis Res. Ther. 2012 14 R20 22284820 PMC3392813
  87. [90]Fingerle-Rowson G Regulation of macrophage migration inhibitory factor expression by glucocorticoids in vivo Am. J. Pathol. 2003 162 47 56 12507889 PMC1851131
  88. [92]Franco LM Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses J. Exp. Med. 2019 216 384 406 30674564 PMC6363437
  89. [94]Barczyk K Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3 Blood 2010 116 446 455 20460503
  90. [95]Huang Y Cai GQ Peng JP Shen C Glucocorticoids induce apoptosis and matrix metalloproteinase-13 expression in chondrocytes through the NOX4/ROS/p38 MAPK pathway J. Steroid Biochem. Mol. Biol. 2018 181 52 62 29526705
  91. [96]Peat G McCarney R Croft P Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care Ann. Rheum. Dis. 2001 60 91 97 11156538 PMC1753462
  92. [97]Hunter DJ McDougall JJ Keefe FJ The symptoms of osteoarthritis and the genesis of pain Rheum. Dis. Clin. North Am. 2008 34 623 643 18687276 PMC2597216
  93. [98]Hannan MT Felson DT Pincus T Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee J. Rheumatol. 2000 27 1513 1517 10852280
  94. [99]Bannuru RR OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis Osteoarthr. Cartil. 2019 27 1578 1589 31278997
  95. [100]Hochberg MC American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee Arthritis Care Res. 2012 64 465 474 22563589
  96. [101]Jafarzadeh SR Felson DT Updated estimates suggest a much higher prevalence of arthritis in United States adults than previous ones Arthritis Rheum. 2018 70 185 192 PMC5788727 29178176
  97. [102]Martin JA Brown TD Heiner AD Buckwalter JA Chondrocyte senescence, joint loading and osteoarthritis Clin. Orthop. Relat. Res. 2004 427 S96 S103 15480082
  98. [103]Gao SG Correlation between senescence-associated beta-galactosidase expression in articular cartilage and disease severity of patients with knee osteoarthritis Int. J. Rheum. Dis. 2016 19 226 232 26112901
  99. [105]Singh P Marcu KB Goldring MB Otero M Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy Ann. N. Y. Acad. Sci. 2019 1442 17 34 30008181
  100. [106]Wu W Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13 Arthritis Rheum. 2002 46 2087 2094 12209513
  101. [107]Dai SM Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: possible involvement of caveolin 1-induced down-regulation of articular chondrocytes in the pathogenesis of osteoarthritis Arthritis Rheum. 2006 54 818 831 16508959
  102. [108]López-Otín C Blasco MA Partridge L Serrano M Kroemer G The hallmarks of aging Cell 2013 153 1194 1217 23746838 PMC3836174
  103. [109]Harman D The free radical theory of aging: effect of age on serum copper levels J. Gerontol. 1965 20 151 153 14284786
  104. [110]Harman D The biologic clock: the mitochondria? J. Am. Geriatr. Soc. 1972 20 145 147 5016631
  105. [111]Maneiro E Mitochondrial respiratory activity is altered in osteoarthritic human articular chondrocytes Arthritis Rheum. 2003 48 700 708 12632423
  106. [112]Ruiz-Romero C Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance Mol. Cell Proteom. 2009 8 172 189 PMC2713027 18784066
  107. [113]Gavriilidis C Miwa S von Zglinicki T Taylor RW Young DA Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2 Arthritis Rheum. 2013 65 378 387 23138846
  108. [114]Scott JL Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease Ann. Rheum. Dis. 2010 69 1502 1510 20511611 PMC3789136
  109. [115]Koike M Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration Sci. Rep. 2015 5 11722 26108578 PMC4480010
  110. [116]Verzijl N Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis Arthritis Rheum. 2002 46 114 123 11822407
  111. [117]Odetti P Advanced glycation end products and bone loss during aging Ann. N. Y. Acad. Sci. 2005 1043 710 717 16037297
  112. [118]Rasheed Z Akhtar N Haqqi TM Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-κB in human osteoarthritis chondrocytes Rheumatology 2010 50 838 851 21172926 PMC3077911
  113. [119]Loeser RF Articular chondrocytes express the receptor for advanced glycation end products: potential role in osteoarthritis Arthritis Rheum. 2005 52 2376 2385 16052547 PMC1488730
  114. [120]DeGroot J Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis Arthritis Rheum. 2004 50 1207 1215 15077303
  115. [121]Shane Anderson A Loeser RF Why is osteoarthritis an age-related disease? Best. Pract. Res. Clin. Rheumatol. 2010 24 15 26 20129196 PMC2818253
  116. [122]Franceschi C Inflamm-aging. An evolutionary perspective on immunosenescence Ann. N. Y. Acad. Sci. 2000 908 244 254 10911963
  117. [124]Cooper C Risk factors for the incidence and progression of radiographic knee osteoarthritis Arthritis Rheum. 2000 43 995 1000 10817551
  118. [125]Silverwood V Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis Osteoarthr. Cartil. 2015 23 507 515 25447976
  119. [126]Felson DT Zhang Y Anthony JM Naimark A Anderson JJ Weight loss reduces the risk for symptomatic knee osteoarthritis in women: the Framingham Study Ann. Intern. Med. 1992 116 535 539 1543306
  120. [127]Atukorala I Is there a dose-response relationship between weight loss and symptom improvement in persons with knee osteoarthritis? Arthritis Care Res. 2016 68 1106 1114 26784732
  121. [128]Runhaar J Prevention of incident knee osteoarthritis by moderate weight loss in overweight and obese females Arthritis Care Res. 2016 68 1428 1433 26866630
  122. [129]Riddle DL Stratford PW Body weight changes and corresponding changes in pain and function in persons with symptomatic knee osteoarthritis: a cohort study Arthritis Care Res. 2013 65 15 22 PMC3401342 22505346
  123. [130]Reyes C Association between overweight and obesity and risk of clinically diagnosed knee, hip, and hand osteoarthritis: a population-based cohort study Arthritis Rheumatol. 2016 68 1869 1875 27059260 PMC4966641
  124. [131]Leyland KM Obesity and the relative risk of knee replacement surgery in patients with knee osteoarthritis: a prospective cohort study Arthritis Rheumatol. 2016 68 817 825 26556722
  125. [132]Messier SP Gutekunst DJ Davis C DeVita P Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis Arthritis Rheum. 2005 52 2026 2032 15986358
  126. [133]Blazek K Favre J Asay J Erhart-Hledik J Andriacchi T Age and obesity alter the relationship between femoral articular cartilage thickness and ambulatory loads in individuals without osteoarthritis J. Orthop. Res. 2014 32 394 402 24281940
  127. [134]Carman WJ Sowers M Hawthorne VM Weissfeld LA Obesity as a risk factor for osteoarthritis of the hand and wrist: a prospective study Am. J. Epidemiol. 1994 139 119 129 8296779
  128. [135]Marshall M Subsets of symptomatic hand osteoarthritis in community-dwelling older adults in the United Kingdom: prevalence, inter-relationships, risk factor profiles and clinical characteristics at baseline and 3-years Osteoarthr. Cartil. 2013 21 1674 1684 23954700 PMC3819994
  129. [136]Cicuttini FM Baker JR Spector TD The association of obesity with osteoarthritis of the hand and knee in women: a twin study J. Rheumatol. 1996 23 1221 1226 8823696
  130. [137]Grotle M Hagen KB Natvig B Dahl FA Kvien TK Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up BMC Musculoskelet. Disord. 2008 9 132 18831740 PMC2573886
  131. [138]Elliott KS Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data Ann. Rheum. Dis. 2013 72 935 941 22956599 PMC3664369
  132. [139]Zhai G Ding C Stankovich J Cicuttini F Jones G The genetic contribution to longitudinal changes in knee structure and muscle strength: a sibpair study Arthritis Rheumatol. 2005 52 2830 2834 16145664
  133. [140]Zhai G Hart DJ Kato BS MacGregor A Spector TD Genetic influence on the progression of radiographic knee osteoarthritis: a longitudinal twin study Osteoarthr. Cartil. 2007 15 222 225 17045816
  134. [141]Neame RL Muir K Doherty S Doherty M Genetic risk of knee osteoarthritis: a sibling study Ann. Rheum. Dis. 2004 63 1022 1027 15308512 PMC1755130
  135. [142]min JL Meulenbelt I Kloppenburg M van Duijn CM Slagboom PE Mutation analysis of candidate genes within the 2q33.3 linkage area for familial early-onset generalised osteoarthritis Eur. J. Hum. Genet. 2007 15 791 799 17406639
  136. [143]Ingvarsson T A large Icelandic family with early osteoarthritis of the hip associated with a susceptibility locus on chromosome 16p Arthritis Rheum. 2001 44 2548 2555 11710711
  137. [144]Jakkula E The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis Osteoarthr. Cartil. 2005 13 497 507 15922184
  138. [145]Liu J Cai W Zhang H He C Deng L Rs143383 in the growth differentiation factor 5 (GDF5) gene significantly associated with osteoarthritis (OA)—a comprehensive meta-analysis Int J. Med. Sci. 2013 10 312 319 23423687 PMC3575627
  139. [146]Tawonsawatruk T A genetic association study between growth differentiation factor 5 (GDF 5) polymorphism and knee osteoarthritis in Thai population J. Orthop. Surg. Res. 2011 6 47 21936909 PMC3189142
  140. [147]Miyamoto Y A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis Nat. Genet. 2007 39 529 533 17384641
  141. [148]Harada M Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5 Osteoarthr. Cartil. 2007 15 468 474 17052922
  142. [149]Buxton P Edwards C Archer CW Francis-West P Growth/differentiation factor-5 (GDF-5) and skeletal development JBJS 2001 83 S23 S30 11263662
  143. [150]Kraus VB Blanco FJ Englund M Karsdal MA Lohmander LS Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use Osteoarthr. Cartil. 2015 23 1233 1241 25865392 PMC4516635
  144. [151]Grynpas MD Alpert B Katz I Lieberman I Pritzker KPH Subchondral bone in osteoarthritis Calcif. Tissue Int. 1991 49 20 26 1893292
  145. [152]Cox LGE van Donkelaar CC van Rietbergen B Emans PJ Ito K Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis Bone 2012 50 1152 1161 22342798
  146. [153]Couchourel D Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production Arthritis Rheum. 2009 60 1438 1450 19404930 PMC5250342
  147. [154]Kellgren JH Lawrence JS Radiological assessment of osteo-arthrosis Ann. Rheum. Dis. 1957 16 494 502 13498604 PMC1006995
  148. [155]Spector TD Definition of osteoarthritis of the knee for epidemiological studies Ann. Rheum. Dis. 1993 52 790 794 8250610 PMC1005190
  149. [156]Altman R Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association Arthritis Rheum. 1986 29 1039 1049 3741515
  150. [157]Singh S Jones BJ Crawford R Xiao Y Characterization of a mesenchymal-like stem cell population from osteophyte tissue Stem Cells Dev. 2008 17 245 254 18447640
  151. [158]Felson DT Osteophytes and progression of knee osteoarthritis Rheumatology 2004 44 100 104 15381791
  152. [159]Nagaosa Y Lanyon P Doherty M Characterisation of size and direction of osteophyte in knee osteoarthritis: a radiographic study Ann. Rheum. Dis. 2002 61 319 324 11874834 PMC1754047
  153. [160]van der Kraan PM van den Berg WB Osteophytes: relevance and biology Osteoarthr. Cartil. 2007 15 237 244 17204437
  154. [161]Pritzker KPH Osteoarthritis cartilage histopathology: grading and staging Osteoarthr. Cartil. 2006 14 13 29 16242352
  155. [162]Glasson SS Chambers MG Van Den Berg WB Little CB The OARSI histopathology initiative—recommendations for histological assessments of osteoarthritis in the mouse Osteoarthr. Cartil. 2010 18 S17 S23 20864019
  156. [163]Buckwalter JA Mankin HJ Grodzinsky AJ Articular cartilage and osteoarthritis Instr. Course Lect. 2005 54 465 480 15952258
  157. [164]Collins DH McElligott TF Sulphate (35SO4) uptake by chondrocytes in relation to histological changes in osteoarthritic human articular cartilage Ann. Rheum. Dis. 1960 19 318 330 13694746 PMC1007162
  158. [165]McDevitt CA Muir H Biochemical changes in the cartilage of the knee in experimental and natural osteoarthritis in the dog J. Bone Jt. Surg. Br. 1976 58 94 101 131804
  159. [166]von der Mark K Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy Arthritis Rheum. 1992 35 806 811 1622419
  160. [167]Blanco FJ Ochs RL Schwarz H Lotz M Chondrocyte apoptosis induced by nitric oxide Am. J. Pathol. 1995 146 75 85 7856740 PMC1870754
  161. [168]Radin EL Paul IL Rose RM Role of mechanical factors in pathogenesis of primary osteoarthritis Lancet 1972 1 519 522 4110024
  162. [169]Radin EL Mechanical determinants of osteoarthrosis Semin. Arthritis Rheum. 1991 21 12 21 1796301
  163. [170]Castañeda S Roman-Blas JA Largo R Herrero-Beaumont G Osteoarthritis: a progressive disease with changing phenotypes Rheumatology 2013 53 1 3 23878311
  164. [171]Aho O-M Finnilä M Thevenot J Saarakkala S Lehenkari P Subchondral bone histology and grading in osteoarthritis PLOS One 2017 12 e0173726 28319157 PMC5358796
  165. [172]Brown TD Radin EL Martin RB Burr DB Finite element studies of some juxtarticular stress changes due to localized subchondral stiffening J. Biomech. 1984 17 11 24 6715384
  166. [173]Zanetti M Bruder E Romero J Hodler J Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings Radiology 2000 215 835 840 10831707
  167. [174]Inoue H Alterations in the collagen framework of osteoarthritic cartilage and subchondral bone Int. Orthop. 1981 5 47 52 7275407
  168. [175]Hunter DJ Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis Arthritis Rheum. 2006 54 1529 1535 16646037
  169. [176]Tanamas SK Bone marrow lesions in people with knee osteoarthritis predict progression of disease and joint replacement: a longitudinal study Rheumatology 2010 49 2413 2419 20823092
  170. [177]Bowes MA Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the osteoarthritis initiative Ann. Rheum. Dis. 2016 75 1852 1857 26672065
  171. [178]Wluka AE Bone marrow lesions predict increase in knee cartilage defects and loss of cartilage volume in middle-aged women without knee pain over 2 years Ann. Rheum. Dis. 2009 68 850 855 18625617
  172. [179]Zhen G Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis Nat. Med. 2013 19 704 712 23685840 PMC3676689
  173. [180]Xie L Systemic neutralization of TGF-β attenuates osteoarthritis Ann. N. Y. Acad. Sci. 2016 1376 53 64 26837060 PMC4970979
  174. [181]Tang Y TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation Nat. Med. 2009 15 757 765 19584867 PMC2727637
  175. [182]Wang Y Correlation between plasma, synovial fluid and articular cartilage interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee Clin. Exp. Med. 2014 14 297 304 23958877
  176. [183]Chen Y Subchondral trabecular rod loss and plate thickening in the development of osteoarthritis J. Bone Miner. Res. 2018 33 316 327 29044705
  177. [184]Shiraishi K In vivo analysis of subchondral trabecular bone in patients with osteoarthritis of the knee using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) Bone 2020 132 115155 31733422
  178. [185]Fukushima K Relationship between synovial inflammatory cytokines and progression of osteoarthritis after hip arthroscopy: experimental assessment J. Orthop. Surg. 2018 26 2309499018770922 29665766
  179. [186]Felson DT Synovitis and the risk of knee osteoarthritis: the MOST study Osteoarthr. Cartil. 2016 24 458 464 26432512 PMC4761323
  180. [187]Roemer FW 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 70 1804 1809 21791448 PMC3496084
  181. [188]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 1267 15731292 PMC1755629
  182. [189]Faúndez J Cotoras P Irarrázaval S Are intraarticular steroids effective for knee osteoarthritis? Medwave 2016 16 e6599 27858928
  183. [190]Raynauld J-P Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial Arthritis Rheum. 2003 48 370 377 12571845
  184. [191]Waarsing JH Bierma-Zeinstra SMA Weinans H Distinct subtypes of knee osteoarthritis: data from the osteoarthritis initiative Rheumatology 2015 54 1650 1658 25882850 PMC4536859
  185. [192]Meulenbelt I Clusters of biochemical markers are associated with radiographic subtypes of osteoarthritis (OA) in subject with familial OA at multiple sites. The GARP study Osteoarthr. Cartil. 2007 15 379 385 17052923
  186. [193]Felson DT Identifying different osteoarthritis phenotypes through epidemiology Osteoarthr. Cartil. 2010 18 601 604 20175975 PMC3474706
  187. [194]Dell’Isola A Steultjens M Classification of patients with knee osteoarthritis in clinical phenotypes: data from the Osteoarthritis Initiative PLoS One 2018 13 e0191045 29329325 PMC5766143
  188. [195]Little CB Zaki S What constitutes an “animal model of osteoarthritis”—the need for consensus? Osteoarthr. Cartil. 2012 20 261 267 22321719
  189. [196]Cole TJ Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation Genes Dev. 1995 9 1608 1621 7628695
  190. [197]Li A Deletion of mesenchymal glucocorticoid receptor attenuates embryonic lung development and abdominal wall closure PLOS One 2013 8 e63578 23696835 PMC3656055
  191. [198]Zhou H Glucocorticoid-dependent Wnt signaling by mature osteoblasts is a key regulator of cranial skeletal development in mice Development 2009 136 427 436 19141672
  192. [200]Mizoguchi K Ishige A Takeda S Aburada M Tabira T Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function J. Neurosci. 2004 24 5492 5499 15201321 PMC6729338
  193. [201]Brewer JA T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation Nat. Med. 2003 9 1318 1322 12949501
  194. [202]Sher LB Transgenic expression of 11β-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone Endocrinology 2004 145 922 929 14617568
  195. [203]Kalak R Endogenous glucocorticoid signalling in osteoblasts is necessary to maintain normal bone structure in mice Bone 2009 45 61 67 19358901
  196. [204]Funder JW Pearce PT Smith R Smith AI Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated Science 1988 242 583 585 2845584
  197. [205]Agarwal AK Monder C Eckstein B White PC Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase J. Biol. Chem. 1989 264 18939 18943 2808402
  198. [206]Tannin GM Agarwal AK Monder C New MI White PC The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization J. Biol. Chem. 1991 266 16653 16658 1885595
  199. [207]Edwards CRW Localisation of 11β-hydroxysteroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor Lancet 1988 332 986 989 2902493
  200. [209]Sundahl N Bridelance J Libert C De Bosscher K Beck IM Selective glucocorticoid receptor modulation: new directions with non-steroidal scaffolds Pharmacol. Ther. 2015 152 28 41 25958032

200 of 253 shown

Cited by

Sorted by citations

Authors
Macfarlane, E., Seibel, M. J., & Zhou, H.
Affiliations
The University of Sydney (AU)
Corresponding author
  • Macfarlane, Eugenie
  • Zhou, Hong
ORCID
Venue
Bone Research
Publisher
Springer Science and Business Media LLC
Published
2020-09-08
Volume
8
Issue
1
Pages
33-33
ISSN
  • 2095-4700 (ISSN-L)
  • 2095-6231
DOI
10.1038/s41413-020-00112-2
PMC
PMC7478967
OpenAlex
W3084192944
Cited by
64
References
15
Citations by year
2026: 6 · 2025: 10 · 2024: 18 · 2023: 9 · 2022: 12 · 2021: 8 · 2020: 1
FWCI
1.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Bone Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Australian Government
  • Medical Research Council
  • National Health and Medical Research Council (1087271, 632818, 1143980)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
endogenous glucocorticoids, rheumatoid arthritis, osteoarthritis, glucocorticoid signaling, joint destruction, articular cartilage, synovium, macrophages, mast cells, chondrocytes, synovial fibroblasts, osteoblasts, osteocytes, aging, pro-inflammatory microenvironment, mouse model

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