Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Jun 2005; 64(6): 886–890.
PMCID: PMC1755507

Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein


Background: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders—for example, rheumatoid arthritis.

Objective: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)—a marker of articular cartilage destruction.

Methods: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA.

Results: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease.

Conclusion: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker.

Full Text

The Full Text of this article is available as a PDF (79K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Iannone Florenzo, Lapadula Giovanni. The pathophysiology of osteoarthritis. Aging Clin Exp Res. 2003 Oct;15(5):364–372. [PubMed]
  • Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, Heyse SP, Hirsch R, Hochberg MC, Hunder GG, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998 May;41(5):778–799. [PubMed]
  • Loeser RF., Jr Aging and the etiopathogenesis and treatment of osteoarthritis. Rheum Dis Clin North Am. 2000 Aug;26(3):547–567. [PubMed]
  • Sell DR, Monnier VM. Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. J Biol Chem. 1989 Dec 25;264(36):21597–21602. [PubMed]
  • Verzijl N, DeGroot J, Oldehinkel E, Bank RA, Thorpe SR, Baynes JW, Bayliss MT, Bijlsma JW, Lafeber FP, Tekoppele JM. Age-related accumulation of Maillard reaction products in human articular cartilage collagen. Biochem J. 2000 Sep 1;350(Pt 2):381–387. [PMC free article] [PubMed]
  • DeGroot J, Verzijl N, Bank RA, Lafeber FP, Bijlsma JW, TeKoppele JM. Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation. Arthritis Rheum. 1999 May;42(5):1003–1009. [PubMed]
  • DeGroot J, Verzijl N, Wenting-Van Wijk MJ, Bank RA, Lafeber FP, Bijlsma JW, TeKoppele JM. Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: the role of advanced glycation end products. Arthritis Rheum. 2001 Nov;44(11):2562–2571. [PubMed]
  • Verzijl Nicole, DeGroot Jeroen, Ben Zaken Chaya, Brau-Benjamin Orit, Maroudas Alice, Bank Ruud A, Mizrahi Joe, Schalkwijk Casper G, Thorpe Suzanne R, Baynes John W, et al. 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 Jan;46(1):114–123. [PubMed]
  • DeGroot Jeroen, Verzijl Nicole, Wenting-van Wijk Marion J G, Jacobs Kim M G, Van El Benno, Van Roermund Peter M, Bank Ruud A, Bijlsma Johannes W J, TeKoppele Johan M, Lafeber Floris P J G. Accumulation of advanced glycation end products as a molecular mechanism for aging as a risk factor in osteoarthritis. Arthritis Rheum. 2004 Apr;50(4):1207–1215. [PubMed]
  • Sugiyama S, Miyata T, Ueda Y, Tanaka H, Maeda K, Kawashima S, Van Ypersele de Strihou C, Kurokawa K. Plasma levels of pentosidine in diabetic patients: an advanced glycation end product. J Am Soc Nephrol. 1998 Sep;9(9):1681–1688. [PubMed]
  • Miyata T, Iida Y, Horie K, Cai Z, Sugiyama S, Maeda K. Pathophysiology of advanced glycation end-products in renal failure. Nephrol Dial Transplant. 1996;11 (Suppl 5):27–30. [PubMed]
  • Takahashi M, Kushida K, Ohishi T, Kawana K, Hoshino H, Uchiyama A, Inoue T. Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders. Arthritis Rheum. 1994 May;37(5):724–728. [PubMed]
  • Chen JR, Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis. J Rheumatol. 1998 Dec;25(12):2440–2444. [PubMed]
  • Chen JR, Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Comparison of the concentrations of pentosidine in the synovial fluid, serum and urine of patients with rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford) 1999 Dec;38(12):1275–1278. [PubMed]
  • Miyata T, Ishiguro N, Yasuda Y, Ito T, Nangaku M, Iwata H, Kurokawa K. Increased pentosidine, an advanced glycation end product, in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with inflammatory markers. Biochem Biophys Res Commun. 1998 Mar 6;244(1):45–49. [PubMed]
  • Pavelka K, Forejtová S, Olejárová M, Gatterová J, Senolt L, Spacek P, Braun M, Hulejová M, Stovícková J, Pavelková A. Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis. Osteoarthritis Cartilage. 2004 Apr;12(4):277–283. [PubMed]
  • Gibson GJ, Verner JJ, Nelson FR, Lin DL. Degradation of the cartilage collagen matrix associated with changes in chondrocytes in osteoarthrosis. Assessment by loss of background fluorescence and immunodetection of matrix components. J Orthop Res. 2001 Jan;19(1):33–42. [PubMed]
  • Larsson E, Erlandsson Harris H, Lorentzen JC, Larsson A, Månsson B, Klareskog L, Saxne T. Serum concentrations of cartilage oligomeric matrix protein, fibrinogen and hyaluronan distinguish inflammation and cartilage destruction in experimental arthritis in rats. Rheumatology (Oxford) 2002 Sep;41(9):996–1000. [PubMed]
  • Neidhart M, Hauser N, Paulsson M, DiCesare PE, Michel BA, Häuselmann HJ. Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation. Br J Rheumatol. 1997 Nov;36(11):1151–1160. [PubMed]
  • Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. 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 Aug;29(8):1039–1049. [PubMed]
  • Pavelká K, Gatterová J, Gollerova V, Urbanová Z, Sedlácková M, Altman RD. A 5-year randomized controlled, double-blind study of glycosaminoglycan polysulphuric acid complex (Rumalon) as a structure modifying therapy in osteoarthritis of the hip and knee. Osteoarthritis Cartilage. 2000 Sep;8(5):335–342. [PubMed]
  • Vilím Vladimír, Vobůrka Zdenek, Vytásek Richard, Senolt Ladislav, Tchetverikov Ilja, Kraus Virginia B, Pavelka Karel. Monoclonal antibodies to human cartilage oligomeric matrix protein: epitope mapping and characterization of sandwich ELISA. Clin Chim Acta. 2003 Feb;328(1-2):59–69. [PubMed]
  • Aigner T, McKenna L. Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci. 2002 Jan;59(1):5–18. [PubMed]
  • Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR. Osteoarthritis or osteoarthrosis: the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthritis Cartilage. 2002 Jan;10(1):1–4. [PubMed]
  • Spector TD, Hart DJ, Nandra D, Doyle DV, Mackillop N, Gallimore JR, Pepys MB. Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum. 1997 Apr;40(4):723–727. [PubMed]
  • Stürmer T, Brenner H, Koenig W, Günther K-P. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis. 2004 Feb;63(2):200–205. [PMC free article] [PubMed]
  • Saxne T, Heinegård D. Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol. 1992 Sep;31(9):583–591. [PubMed]
  • Vilím V, Olejárová M, Machácek S, Gatterová J, Kraus VB, Pavelka K. Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage. 2002 Sep;10(9):707–713. [PubMed]
  • Sharif M, Saxne T, Shepstone L, Kirwan JR, Elson CJ, Heinegård D, Dieppe PA. Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint. Br J Rheumatol. 1995 Apr;34(4):306–310. [PubMed]
  • Hummel KM, Neidhart M, Vilim V, Hauser N, Aicher WK, Gay RE, Gay S, Häuselmann HJ. Analysis of cartilage oligomeric matrix protein (COMP) in synovial fibroblasts and synovial fluids. Br J Rheumatol. 1998 Jul;37(7):721–728. [PubMed]
  • Altman RD, Hochberg M, Murphy WA, Jr, Wolfe F, Lequesne M. Atlas of individual radiographic features in osteoarthritis. Osteoarthritis Cartilage. 1995 Sep;3 (Suppl A):3–70. [PubMed]

Figures and Tables

Figure 1
 Comparison of the serum levels of (A) pentosidine and (B) COMP in patients with OA and in controls.
Figure 2
 Correlation between serum (S) and synovial fluid (SF) levels of (A) pentosidine and (B) COMP in patients with OA.
Figure 3
 Correlation between (A) pentosidine and COMP in synovial fluid (SF) and (B) pentosidine in serum (S) and COMP in SF in patients with OA.
Figure 4
 (A) Serum levels of pentosidine are significantly increased compared with levels in synovial fluid (SF) in patients with OA (p<0.001). (B) In contrast, serum levels of COMP are significantly decreased compared with levels in SF in patients ...

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...