Skip to main content
Top
Published in: Rheumatology International 10/2009

01-08-2009 | Original Article

Characterization of synovial tissue from arthritis patients: a proton magnetic resonance spectroscopic investigation

Authors: Carol A. Hitchon, Hani S. El-Gabalawy, Tedros Bezabeh

Published in: Rheumatology International | Issue 10/2009

Login to get access

Abstract

Hypoxia may contribute to the pathogenesis of synovitis in rheumatoid arthritis (RA). Magnetic resonance spectroscopy (MRS) is a technique that uses radiofrequency waves to generate a signal which allows a qualitative and quantitative assessment of the biochemical composition of tissue. MRS was used to evaluate RA synovial tissue for evidence of hypoxia and anaerobic metabolism. Synovial tissue samples obtained from eighteen RA patients and four osteoarthritis control patients undergoing total knee replacement were analyzed using proton MRS, processed for histopathology and scored for inflammation and vascularity. Spectra from severely and mildly inflamed tissue differed in peak intensity at regions 1.3 ppm (representing lactic acid and lipid), 3.0 ppm (representing creatine), 3.2 ppm (representing choline containing metabolites), and 3.8 ppm (representing carbohydrates, possibly glucose). With increasing inflammation, the intensities of the peak resonance at 1.3 ppm increased and that at 3.8 ppm decreased. The intensities of the 3.8 and 3.0 ppm peaks were reduced in highly vascular tissue. Specific MR spectral features reflect the anaerobic metabolism that is evident with progressively increasing degrees of RA synovial inflammation and vascularity. These features correlate partially with synovial histopathology.
Literature
3.
go back to reference Naughton DP, Haywood R, Blake DR et al (1993) A comparative evaluation of the metabolic profiles of normal and inflammatory knee-joint synovial fluids by high resolution proton NMR spectroscopy. FEBS Lett 332(3):221–225. doi:10.1016/0014-5793(93)80636-9 PubMedCrossRef Naughton DP, Haywood R, Blake DR et al (1993) A comparative evaluation of the metabolic profiles of normal and inflammatory knee-joint synovial fluids by high resolution proton NMR spectroscopy. FEBS Lett 332(3):221–225. doi:10.​1016/​0014-5793(93)80636-9 PubMedCrossRef
4.
go back to reference Naughton D, Whelan M, Smith EC et al (1993) An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy. FEBS Lett 317(1–2):135–138. doi:10.1016/0014-5793(93)81508-W PubMedCrossRef Naughton D, Whelan M, Smith EC et al (1993) An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy. FEBS Lett 317(1–2):135–138. doi:10.​1016/​0014-5793(93)81508-W PubMedCrossRef
6.
go back to reference Hitchon CA, Ziouzina O, Hart D et al (2002) Are hypoxic synovial fluid conditions associated with measures of synovial angiogenesis? Arthritis Rheum 9(46):S548 Hitchon CA, Ziouzina O, Hart D et al (2002) Are hypoxic synovial fluid conditions associated with measures of synovial angiogenesis? Arthritis Rheum 9(46):S548
7.
go back to reference Grootveld M, Henderson EB, Farrell A et al (1991) Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r spectroscopy. Biochem J 273(Pt 2):459–467PubMed Grootveld M, Henderson EB, Farrell A et al (1991) Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r spectroscopy. Biochem J 273(Pt 2):459–467PubMed
10.
go back to reference Giatromanolaki A, Sivridis E, Maltezos E et al (2003) Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 5(4):R193–R201. doi:10.1186/ar756 PubMedCrossRef Giatromanolaki A, Sivridis E, Maltezos E et al (2003) Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 5(4):R193–R201. doi:10.​1186/​ar756 PubMedCrossRef
11.
go back to reference Hitchon C, Wong K, Ma G et al (2002) Hypoxia-induced production of stromal cell-derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblasts. Arthritis Rheum 46(10):2587–2597. doi:10.1002/art.10520 PubMedCrossRef Hitchon C, Wong K, Ma G et al (2002) Hypoxia-induced production of stromal cell-derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblasts. Arthritis Rheum 46(10):2587–2597. doi:10.​1002/​art.​10520 PubMedCrossRef
12.
go back to reference Singh D, Nazhat NB, Fairburn K et al (1995) Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen species by diseased human synovial tissue following ex vivo hypoxia–reoxygenation. Ann Rheum Dis 54(2):94–99. doi:10.1136/ard.54.2.94 PubMedCrossRef Singh D, Nazhat NB, Fairburn K et al (1995) Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen species by diseased human synovial tissue following ex vivo hypoxia–reoxygenation. Ann Rheum Dis 54(2):94–99. doi:10.​1136/​ard.​54.​2.​94 PubMedCrossRef
13.
go back to reference Peters CL, Morris CJ, Mapp PI et al (2004) The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. Arthritis Rheum 50(1):291–296. doi:10.1002/art.11473 PubMedCrossRef Peters CL, Morris CJ, Mapp PI et al (2004) The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. Arthritis Rheum 50(1):291–296. doi:10.​1002/​art.​11473 PubMedCrossRef
17.
go back to reference Smith ICP, Bezabeh T (2000) Tissue NMR ex vivo. In: Young IR (ed) Methods in biomedical magnetic resonance imaging and spectroscopy. Wiley, Chichester, pp 891–897 Smith ICP, Bezabeh T (2000) Tissue NMR ex vivo. In: Young IR (ed) Methods in biomedical magnetic resonance imaging and spectroscopy. Wiley, Chichester, pp 891–897
19.
go back to reference El-Sayed S, Bezabeh T, Odlum O et al (2002) An ex-vivo study exploring the diagnostic potential of 1H magnetic resonance spectroscopy in squamous cell carcinoma of the head and neck region. Head Neck 24(8):766–772. doi:10.1002/hed.10125 PubMedCrossRef El-Sayed S, Bezabeh T, Odlum O et al (2002) An ex-vivo study exploring the diagnostic potential of 1H magnetic resonance spectroscopy in squamous cell carcinoma of the head and neck region. Head Neck 24(8):766–772. doi:10.​1002/​hed.​10125 PubMedCrossRef
20.
go back to reference Bezabeh T, Smith IC, Krupnik E et al (1996) Diagnostic potential for cancer via 1H magnetic resonance spectroscopy of colon tissue. Anticancer Res 16(3B):1553–1558PubMed Bezabeh T, Smith IC, Krupnik E et al (1996) Diagnostic potential for cancer via 1H magnetic resonance spectroscopy of colon tissue. Anticancer Res 16(3B):1553–1558PubMed
21.
go back to reference Hahn P, Smith IC, Leboldus L et al (1997) The classification of benign and malignant human prostate tissue by multivariate analysis of 1H magnetic resonance spectra. Cancer Res 57(16):3398–3401PubMed Hahn P, Smith IC, Leboldus L et al (1997) The classification of benign and malignant human prostate tissue by multivariate analysis of 1H magnetic resonance spectra. Cancer Res 57(16):3398–3401PubMed
23.
go back to reference Lean CL, Mackinnon WB, Delikatny EJ et al (1992) Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. Biochemistry 31(45):11095–11105. doi:10.1021/bi00160a020 PubMedCrossRef Lean CL, Mackinnon WB, Delikatny EJ et al (1992) Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. Biochemistry 31(45):11095–11105. doi:10.​1021/​bi00160a020 PubMedCrossRef
26.
go back to reference Altman R, Asch E, Bloch D et al (1986) 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 29(8):1039–1049. doi:10.1002/art.1780290816 PubMedCrossRef Altman R, Asch E, Bloch D et al (1986) 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 29(8):1039–1049. doi:10.​1002/​art.​1780290816 PubMedCrossRef
27.
go back to reference Kuesel AC, Kroft T, Saunders JK et al (1992) A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies. Magn Reson Med 27(2):349–355. doi:10.1002/mrm.1910270215 PubMedCrossRef Kuesel AC, Kroft T, Saunders JK et al (1992) A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies. Magn Reson Med 27(2):349–355. doi:10.​1002/​mrm.​1910270215 PubMedCrossRef
28.
29.
go back to reference Listinsky JJ, Siegal GP, Listinsky CM (1998) Alpha-l-fucose: a potentially critical molecule in pathologic processes including neoplasia. Am J Clin Pathol 110(4):425–440PubMed Listinsky JJ, Siegal GP, Listinsky CM (1998) Alpha-l-fucose: a potentially critical molecule in pathologic processes including neoplasia. Am J Clin Pathol 110(4):425–440PubMed
30.
go back to reference Somorjai RL, Alexander M, Baumgartner R et al (2004) A data-driven, flexible machine learning strategy for the classification of biomedical data. In: Dubitzky W, Azuaje F (eds) Artificial intelligence methods and tools for systems biology, computational biology series, vol 5. Springer, Berlin, pp 67–85 Somorjai RL, Alexander M, Baumgartner R et al (2004) A data-driven, flexible machine learning strategy for the classification of biomedical data. In: Dubitzky W, Azuaje F (eds) Artificial intelligence methods and tools for systems biology, computational biology series, vol 5. Springer, Berlin, pp 67–85
31.
go back to reference Higai K, Aoki Y, Azuma Y, Matsumoto K (2005) Glycosylation of site-specific glycans of alpha1-acid glycoprotein and alterations in acute and chronic inflammation. Biochim Biophys Acta 1725(1):128–135PubMed Higai K, Aoki Y, Azuma Y, Matsumoto K (2005) Glycosylation of site-specific glycans of alpha1-acid glycoprotein and alterations in acute and chronic inflammation. Biochim Biophys Acta 1725(1):128–135PubMed
33.
go back to reference Wang Y, Holmes E, Comelli EM et al (2007) Topographical variation in metabolic signatures of human gastrointestinal biopsies revealed by high-resolution magic-angle spinning 1H NMR spectroscopy. J Proteome Res 6(10):3944–3951. doi:10.1021/pr0702565 PubMedCrossRef Wang Y, Holmes E, Comelli EM et al (2007) Topographical variation in metabolic signatures of human gastrointestinal biopsies revealed by high-resolution magic-angle spinning 1H NMR spectroscopy. J Proteome Res 6(10):3944–3951. doi:10.​1021/​pr0702565 PubMedCrossRef
Metadata
Title
Characterization of synovial tissue from arthritis patients: a proton magnetic resonance spectroscopic investigation
Authors
Carol A. Hitchon
Hani S. El-Gabalawy
Tedros Bezabeh
Publication date
01-08-2009
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 10/2009
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-009-0865-z

Other articles of this Issue 10/2009

Rheumatology International 10/2009 Go to the issue