CoChat
Sign Up
Cited by 362Osteoarthritis Treatment and MechanismsRheumatoid Arthritis Research and TherapiesBiomarkers in Disease Mechanisms

Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis

Open access
Pearle, A.D., Scanzello, C.R., George, S., Mandl, L.A., DiCarlo, E.F., Peterson, M., Sculco, T.P., Crow, M.K.·2007·Osteoarthritis and Cartilage
DOI 10.1016/j.joca.2006.10.010
Open this paper in CoChat — free accountOpen PDF

Abstract

Objective C-reactive protein (CRP) has been associated with disease progression in patients with osteoarthritis (OA), but the reasons for this remain unclear. We hypothesized that higher CRP would be related to local inflammatory findings in the joints of patients with OA. Methods Plasma and synovial membrane specimens from 54 OA patients undergoing total hip or knee arthroplasty or arthroscopy were obtained. Synovial fluid was obtained from 25 of these patients. Hematoxylin and eosin stained synovial membrane sections were scored for degree of inflammatory cell infiltration. Plasma high-sensitivity CRP (hsCRP) levels, and serum and synovial fluid interleukin (IL)-6 and IL-1beta levels were measured by enzyme-linked immunosorbent assay. Results Fifty-seven percent of patients with idiopathic OA had inflammatory infiltrates within the synovial membrane. The mean hsCRP level in patients with inflammatory infiltrates was significantly higher than those without inflammation (4.7 +/- 5.0 mg/L vs 1.7 +/- 3.6 mg/L, P = 0.003). There were significant correlations between hsCRP levels and synovial fluid IL-6 (r = 0.64, P = 0.0006), degree of synovial inflammatory infiltration (r = 0.43, P = 0.002), and body mass index (r = 0.31, P = 0.02). Multivariate analysis indicated that only degree of inflammatory infiltrate was significantly associated with hsCRP level (P = 0.026). Conclusion These results suggest that systemic hsCRP levels reflect synovial inflammation in OA patients, perhaps by means of synovial IL-6 production. Future studies are needed to clarify how these infiltrates and their products may contribute to disease pathogenesis.

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.joca.2006.10.010

Cites

3 of 3 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?

  • IL-6 levels in OA fluid correlate with pain, synovial proliferation, and cartilage degradation indicators and control cartilage and bone metabolism.

    “By MMP induction and RANKL/OPG axis control, IL-6 levels in OA fluid correlate with pain, synovial proliferation, and cartilage degradation indicators and control cartilage and bone metabolism [48,49].”

    From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [48]

    The IL-6 and IL-1β results section (page not available) reports a trend toward correlation between synovial-fluid IL-6 and inflammatory-cell infiltration in a subset of patients with advanced OA. The Discussion links pain and cartilage loss to synovitis or hsCRP, not directly to IL-6 levels. It does not establish correlations with synovial proliferation or cartilage-degradation indicators, or show IL-6 controlling cartilage and bone metabolism through MMPs or the RANKL/OPG axis. (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: 43

  1. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, et al. Statin therapy, LDL choles- terol, C-reactive protein, and coronary artery disease. N Engl J Med 2005;352:29e38.
  2. Hashimoto H, Kitagawa K, Hougaku H, Shimizu Y, Sakaguchi M, Nagai Y, et al. C-reactive protein is an independent predictor of the rate of increase in early carotid atherosclerosis. Circulation 2001;104:63e7.
  3. Rossi E, Biasucci LM, Citterio F, Pelliccioni S, Monaco C, Ginnetti F, et al. Risk of myocardial infarc- tion and angina in patients with severe peripheral vascular disease: predictive role of C-reactive protein. Circulation 2002;105:800e3.
  4. Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103:1813e8.
  5. Burke AP, Tracy RP, Kolodgie F, Malcom GT, Zieske A, Kutys R, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: associ- ation with different pathologies. Circulation 2002;105: 2019e23.
  6. Du Clos TW, Mold C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res 2004;30:261e77. 521 Osteoarthritis and Cartilage Vol. 15, No. 5
  7. Mold C, Rodriguez W, Rodic-Polic B, Du Clos TW. C- reactive protein mediates protection from lipopolysac- charide through interactions with Fc gamma R. J Immunol 2002;169:7019e25.
  8. Labarrere CA, Zaloga GP. C-reactive protein: from inno- cent bystander to pivotal mediator of atherosclerosis. Am J Med 2004;117:499e507.
  9. Ballou SP, Lozanski G. Induction of inflammatory cyto- kine release from cultured human monocytes by C-re- active protein. Cytokine 1992;4:361e8.
  10. Pasceri V, Chang J, Willerson JT, Yeh ETH. Modulation of C-reactive protein-mediated monocyte chemoat- tractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001;103: 2531e4.
  11. Wolfe F. The C-reactive protein but not erythrocyte sed- imentation rate is associated with clinical severity in patients with osteoarthritis of the knee or hip. J Rheu- matol 1997;8:1486e8.
  12. Conrozier T, Carlier MC, Mathieu P, Colson F, Debard AL, Richard S, et al. Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis and healthy subjects: a cross sectional study. Ann Rheum Dis 2000;59:828e31.
  13. Sowers M, Jannausch M, Stein E, Jamadar D, Hochberg M, Lachance L. C-reactive protein as a biomarker of emergent osteoarthritis. Osteoarthritis Cartilage 2002;10:595e601.
  14. Sturmer T, Brenner H, Koenig W, Gunther KP. Severity and extent of osteoarthritis and low grade systemic in- flammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis 2004;63:200e5.
  15. Verhave JC, Hillege HL, Burgerhof JG, Gansevoort RT, de Zeeuw D, de Jong PE. The association between atherosclerotic risk factors and renal function in the general population. Kidney Int 2005;67:1967e73.
  16. Conrozier T, Chappuis-Cellier C, Richard M, Mathieu P, Richard S, Vignon E. Increased serum C-reactive pro- tein levels by immunonephelometry in patients with rapidly destructive hip osteoarthritis. Rev Rhum Engl Ed 1998;65:759e65.
  17. Sharif M, Shepstone L, Elson CJ, Dieppe PA, Kirwan JR. Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee. Ann Rheum Dis 2000;59:71e4.
  18. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classi- fication and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeu- tic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29:1039e49.
  19. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957;16:494e502.
  20. Myers SL, Brandt KD, Ehlich JW, Braunstein EM, Shelbourne KD, Heck DA, et al. Synovial inflammation in patients with early osteoarthritis of the knee. J Rheumatol 1990;17:1662e9.
  21. Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: a histological study includ- ing the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal anti- bodies. Ann Rheum Dis 1988;47:300e7.
  22. Goldenberg D, Egan M, Cohen A. Inflammatory synovi- tis in degenerative joint disease. J Rheumatol 1982;9: 204e9.
  23. Kraus VB, Huebner JL, Fink C, King JB, Brown S, Vail TP, et al. Urea as a passive transport marker for arthritis biomarker studies. Arthritis Rheum 2002;46: 420e7.
  24. Godefroi R, Klementowicz P, Pepler C, Lewis B, McDonough K, Goldberg RJ. Levels of, and factors as- sociated with, C-reactive protein in employees attend- ing a company-sponsored cardiac screening program. Cardiology 2005;103:180e4.
  25. Smith MD, Triantafillou S, Parker A, Youssef PP, Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol 1997;24:365e71.
  26. 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: 1263e7.
  27. Lindblad S, Hedfors E. Arthroscopic and immunohisto- logic characterization of knee joint synovitis in osteoar- thritis. Arthritis Rheum 1987;30:1081e8.
  28. Hill CL, Gale DG, Chaisson CE, Skinner K, Kazis L, Gale ME, et al. Knee effusions, popliteal cysts, and sy- novial thickening: association with knee pain in osteo- arthritis. J Rheumatol 2001;28:1330e7.
  29. Torres L, Dunlop DD, Peterfy C, Guermazi A, Prasad P, Hayes KW, et al. The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis. Osteoarthritis Cartilage 2006;14:1033e40.
  30. Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis e results of a 1 year longitudinal arthro- scopic study in 422 patients. Osteoarthritis Cartilage 2005;13:361e7.
  31. 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;34:799e807.
  32. Otterness IG, Swindell AC, Zimmerer RO, Poole AR, Ionescu M, Weiner E. An analysis of 14 molecular markers for monitoring osteoarthritis: segregation of the markers into clusters and distinguishing osteoar- thritis at baseline. Osteoarthritis Cartilage 2000;8: 180e5.
  33. Bhardwaj N, Santhanam U, Lau LL, Tatter SB, Ghrayeb J, Rivelis M, et al. IL-6/IFN-beta 2 in synovial effusions of patients with rheumatoid arthritis and other arthritides. Identification of several isoforms and studies of cellular sources. J Immunol 1989;143: 2153e9.
  34. Swaak AJ, van Rooyen A, Nieuwenhuis E, Aarden LA. Interleukin-6 (IL-6) in synovial fluid and serum of pa- tients with rheumatic diseases. Scand J Rheumatol 1988;17:469e74.
  35. Uson J, Balsa A, Pascual-Salcedo D, Cabezas JA, Gonzalez-Tarrio JM, Martin-Mola E, et al. Soluble in- terleukin 6 (IL-6) receptor and IL-6 levels in serum and synovial fluid of patients with different arthropa- thies. J Rheumatol 1997;24:2069e75.
  36. Castell JV, Geiger T, Gross V, Andus T, Walter E, Hirano T, et al. Plasma clearance, organ distribu- tion and target cells of interleukin-6/hepatocyte- stimulating factor in the rat. Eur J Biochem 1988; 177:357e61.
  37. McNiff PA, Stewart C, Sullivan J, Showell HJ, Gabel CA. Synovial fluid from rheumatoid arthritis 522 A. D. Pearle et al.: Synovial Inflammation and hsCRP in OA patients contains sufficient levels of IL-1 beta and IL-6 to promote production of serum amyloid A by Hep3B cells. Cytokine 1995;7:209e19.
  38. Hwang SY, Kim JY, Kim KW, Park MK, Moon Y, Kim WW, et al. IL-17 induces production of IL-6 and IL-8 in rheu- matoid arthritis synovial fibroblasts via NF-kappaB- and PI3-kinase/Akt-dependent pathways. Arthritis Res Ther 2004;6:R120e8.
  39. Fiorito S, Magrini L, Adrey J, Mailhe D, Brouty-Boye D. Inflammatory status and cartilage regenerative poten- tial of synovial fibroblasts from patients with osteoarthritis and chondropathy. Rheumatology (Ox- ford) 2005;44:164e71.
  40. Wood NC, Symons JA, Dickens E, Duff GW. In situ hybridization of IL-6 in rheumatoid arthritis. Clin Exp Immunol 1992;87:183e9.
  41. Fan Z, Bau B, Yang H, Aigner T. IL-1beta induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NFkappaB signaling path- ways. Cytokine 2004;28:17e24.
  42. Matsumoto T, Tsurumoto T, Shindo H. Interleukin-6 levels in synovial fluids of patients with rheumatoid ar- thritis correlated with the infiltration of inflammatory cells in synovial membrane. Rheum Int 2006;26: 1096e100.
  43. Aronson D, Goldberg A, Roguin A, Petcherski S, Rimer D, Gruberg L, et al. Effect of obesity on the re- lationship between plasma C-reactive protein and cor- onary artery stenosis in patients with stable angina. Atherosclerosis 2005;185:137e42. 523 Osteoarthritis and Cartilage Vol. 15, No. 5

Cited by

Sorted by citations

Authors
Pearle, A. D., Scanzello, C. R., George, S., Mandl, L. A., DiCarlo, E. F., Peterson, M., Sculco, T. P., & Crow, M. K.
Affiliations
Hospital for Special Surgery (US)
Corresponding author
Scanzello, C.R.
ORCID
Venue
Osteoarthritis and Cartilage
Publisher
Elsevier BV
Published
2007-05
Volume
15
Issue
5
Pages
516-523
ISSN
1063-4584 (ISSN-L)
DOI
10.1016/j.joca.2006.10.010
OpenAlex
W2128488724
Cited by
362
References
3
Citations by year
2026: 14 · 2025: 24 · 2024: 17 · 2023: 19 · 2022: 14 · 2021: 19 · 2020: 17 · 2019: 15 · 2018: 20 · 2017: 30 · 2016: 22 · 2015: 28 · 2014: 18 · 2013: 19 · 2012: 24
FWCI
6.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Osteoarthritis and Cartilage (publishedVersion)
  • PubMed (publishedVersion)
Funders
Orthopaedic Research and Education Foundation
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords
osteoarthritis, high-sensitivity C-reactive protein, synovitis, synovium, interleukin-6, IL-1β, synovial fluid, inflammatory cell infiltration, body mass index, disease progression, arthroplasty
MeSH terms
Adult, Aged, Aged, 80 and over, Arthroscopy, C-Reactive Protein, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Synovial Fluid, Osteoarthritis, Hip, Interleukin-6, Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Osteoarthritis, Knee, Interleukin-1beta

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