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Effects of intra-articular administration of glucosamine and a peptidyl-glucosamine derivative in a rabbit model of experimental osteoarthritis: a pilot study

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Abstract

The aim of this pilot study was to analyze the effects of glucosamine (GlcN) and its N-acetyl-phenylalanine derivative (NAPA) in Vitamin A model of osteoarthritis (OA) in rabbits. GlcN or NAPA or saline solution was intra-articularly administered in rabbit OA knees. Histological analysis revealed that treatment with GlcN or NAPA was associated with more homogeneous chondrocyte cellularity, absence of fissures and fragmentation and more intense staining of the matrix with Alcian Blue compared to the articular surfaces of the knees treated with saline solution. Comparative in vitro study performed on rabbit primary chondrocytes revealed that GlcN and NAPA were also able to counteract the IL-1β-upregulation of genes coding for metalloproteases and inflammatory cytokines. Our preliminary in vivo and in vitro studies suggest that GlcN and NAPA could play a disease-modifying protective role in OA by an anti-catabolic effect and an anti-inflammatory activity on chondrocytes.

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References

  1. Sandell LJ, Aigner T (2001) Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 3:107–113

    Article  PubMed  CAS  Google Scholar 

  2. Loeser RF (2006) Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis Rheum 54:1357–1360

    Article  PubMed  CAS  Google Scholar 

  3. Goldring MB (2000) Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2:459–465

    Article  PubMed  CAS  Google Scholar 

  4. Hamburger MI, Lakhanpal S, Mooar PA, Oster D (2003) Intra-articular hyaluronans: a review of product-specific safety profiles. Semin Arthritis Rheum 32:296–309

    Article  PubMed  CAS  Google Scholar 

  5. Lippiello L, Woodward J, Karpman R, Hammad TA (2000) In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop Relat Res 381:229–240

    Article  PubMed  Google Scholar 

  6. Oegema TR Jr, Deloria LB, Sandy JD, Hart DA (2002) Effect of oral glucosamine on cartilage and meniscus in normal and chymopapain-injected knees of young rabbits. Arthritis Rheum 46:2495–2503

    Article  PubMed  CAS  Google Scholar 

  7. Shikhman AR, Amiel D, D’Lima D, Hawng S-B, Hu C, Xu A, Hashimoto S, Kobayashi K, Sasho T, Lotz M (2005) Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis. Ann Rheum Dis 64:89–94

    Article  PubMed  CAS  Google Scholar 

  8. Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gosset C (2001) Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 357:251–256

    Article  PubMed  CAS  Google Scholar 

  9. Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC (2002) Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 162:2113–2123

    Article  PubMed  CAS  Google Scholar 

  10. Bruyere O, Pavelka K, Rovati LC, Deroisy R, Olejarova M, Gatterova J, Giacovelli G, Reginster JY (2004) Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two years studies. Menopause 11:138–143

    Article  PubMed  Google Scholar 

  11. Grillo MG, Panzini G, Di Virgilio A, Corsi A, Riminucci M, Bianco P, Politi L, Lorenzini RN, Scandurra R (2004) Intra-articular injection of Vitamin A: a rabbit model to study osteoarthrosis. Scand J Lab Anim Sci 31:3–8

    CAS  Google Scholar 

  12. Giordano C, Gallina C, Consalvi V, Scandurra R (1991) Synthesis and properties of d-glucosamine N-peptidyl derivatives as substrate analog inhibitors of papain and cathepsin B. Eur J Med Chem 26:753–762

    Article  CAS  Google Scholar 

  13. Kirschke H, Kembhavi AA, Bohley P, Barrett AJ (1982) Action of rat liver cathepsin L on collagen and other substrates. Biochem J 201:367–372

    PubMed  CAS  Google Scholar 

  14. Martel-Pelletier J, Cloutier JM, Pelletier JP (1990) Cathepsin B and cysteine protease inhibitors in human osteoarthritis. J Orthop Res 8:336–344

    Article  PubMed  CAS  Google Scholar 

  15. Lapadula G, Nico B, Cantatore FP, La Canna R, Roncali L, Pipitone V (1995) Early ultrastructural changes of articular cartilage and synovial membrane in experimental Vitamin A-induced osteoarthritis. J Rheum 22:1913–1921

    PubMed  CAS  Google Scholar 

  16. Gehrsitz A, McKenna LA, Soder S, Kirchner T, Aigner T (2001) Isolation of RNA from small human articular cartilage specimens allows quantification of mRNA expression levels in local articular cartilage defects. J Orthop Res 19(3):478–481

    Article  PubMed  CAS  Google Scholar 

  17. Bassleer C, Rovati L, Franchimont P (1998) Stimulation of proteoglycan production by glucosamine sulfate in chondrocytes isolated from human osteoarthritic articular cartilage in vitro. Osteoarthr Cartil 6:427–434

    Article  PubMed  CAS  Google Scholar 

  18. Dodge GR, Jimenez SA (2003) Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthr Cartil 11:424–432

    Article  PubMed  CAS  Google Scholar 

  19. Mroz PJ, Silbert JE (2004) Use of 3H-glucosamine and 35S-sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate. Arthritis Rheum 50:3574–3579

    Article  PubMed  CAS  Google Scholar 

  20. Mroz PJ, Silbert JE (2003) Effects of [3H]glucosamine concentration on [3H]chondroitin sulphate formation by cultured chondrocytes. Biochem J 376:511–515

    Article  PubMed  CAS  Google Scholar 

  21. Uitterlinden EJ, Jahr H, Koevoet JLM, Jenniskens YM, Bierma-Zeinstra SMA, DeGroot J, Verhaar JA, Weinans H, van Osch GJ (2006) Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants. Osteoarthr Cartil 14:250–257

    Article  PubMed  CAS  Google Scholar 

  22. Qu C-J, Karjalainen HM, Helminen HJ, Lammi MJ (2006) The lack of effect of glucosamine sulphate on aggrecan mRNA expression and (35)S-sulphate incorporation in bovine primary chondrocytes. Biochim Biophys Acta 1762:453–459

    PubMed  CAS  Google Scholar 

  23. Bluteau G, Conrozier T, Mathieu P, Vignon E, Herbage D, Mallein-Gerin F (2001) Matrix metalloporotease-1, -3, -13 and aggrecanase-1 and -2 are differentially expressed in experimental osteoarthritis. Biochim Biophys Acta 1526:147–158

    PubMed  CAS  Google Scholar 

  24. Shlopov BV, Lie W-R, Mainardi CL, Cole AA, Xhubinskaya S, Hasty KA (1997) Osteoarthritic lesions: involvement of three different collagenases. Arthritis Rheum 40:2065–2074

    Article  PubMed  CAS  Google Scholar 

  25. Lotz M (2001) Cytokines in cartilage injury and repair. Clin Orthop Relat Res 391(Suppl):S108–S115

    Article  PubMed  Google Scholar 

  26. Mohtai M, Gupta MK, Donlon B, Ellison B, Cooke J, Gibbons G, Schurman DJ, Smith RL (1996) Expression of interleukin-6 in osteoarthritic chondrocytes and effects of fluid-induced shear on this expression in normal human chondrocytes in vitro. J Orthop Res 14:67–73

    Article  PubMed  CAS  Google Scholar 

  27. Kammermann JR, Kincaid SA, Rumph PF, Baird DK, Visco DM (1996) Tumor necrosis factor-alpha (TNF-alpha) in canine osteoarthritis, immunolocalization of TNF-alpha, stromelysin and TNF receptors in canine osteoarthritic cartilage. Osteoarthr Cartil 4:23–34

    Article  PubMed  CAS  Google Scholar 

  28. Gouze JN, Bordji K, Gulberti S, Terlain B, Netter P, Magdalou J, Fournel-Gigleux S, Ouzzine M (2001) Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis Rheum 44:351–360

    Article  PubMed  CAS  Google Scholar 

  29. Shikhman AR, Kuhn K, Alaaeddine N, Lotz M (2001) N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes. J Immunol 166:5155–5160

    PubMed  CAS  Google Scholar 

  30. Largo R, Alvarez-Soria MA, Diez-Ortega I, Calvo E, Sanchez-Pernaute O, Egido J, Herrero-Beaumont G (2003) Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes. Osteoarthr Cartil 11:290–298

    Article  PubMed  CAS  Google Scholar 

  31. Chan PS, Caron JP, Rosa GJ, Orth MW (2005) Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthr Cartil 13:387–394

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Mr. Antonio Di Virgilio, Mr. Agostino Eusepi and Mr. Luciano Strangio for their help in carrying out the experimental procedures on rabbits.

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Authors and Affiliations

  1. Dipartimento di Scienze Biochimiche, Sapienza Università di Roma, P.le Aldo Moro, 5, 00185, Rome, Italy

    Anna Scotto d’Abusco, Claudia Cicione, Valentina Calamia, Laura Politi & Roberto Scandurra

  2. Dipartimento di Medicina Sperimentale e Patologia, Sapienza Università di Roma, V.le Regina Elena, 324, 00161, Rome, Italy

    Alessandro Corsi

  3. Dipartimento di Ortopedia e Traumatologia, Ospedale Iazzolino, P.zza Fleming, 89900, Vibo Valentia, Italy

    Maria Grazia Grillo

  4. Servizio di Qualità e sicurezza della sperimentazione animale, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy

    Gianluca Panzini

  5. Istituto di Chimica Biomolecolare del CNR, Sapienza Università di Roma, P.le A. Moro 5, 00185, Rome, Italy

    Anna Sansone & Cesare Giordano

Authors
  1. Anna Scotto d’Abusco
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  2. Alessandro Corsi
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  3. Maria Grazia Grillo
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  4. Claudia Cicione
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  5. Valentina Calamia
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  6. Gianluca Panzini
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  7. Anna Sansone
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  8. Cesare Giordano
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  9. Laura Politi
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  10. Roberto Scandurra
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Correspondence to Anna Scotto d’Abusco.

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Scotto d’Abusco, A., Corsi, A., Grillo, M.G. et al. Effects of intra-articular administration of glucosamine and a peptidyl-glucosamine derivative in a rabbit model of experimental osteoarthritis: a pilot study. Rheumatol Int 28, 437–443 (2008). https://doi.org/10.1007/s00296-007-0463-x

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  • DOI: https://doi.org/10.1007/s00296-007-0463-x

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