Skip to main content

Advertisement

SpringerLink
Log in

Chondroitin sulphate: a focus on osteoarthritis

  • Mini-Review
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Chondroitin sulfate (CS) being a natural glycosaminoglycan is found in the cartilage and extracellular matrix. It shows clinical benefits in symptomatic osteoarthritis (OA) of the finger, knee, hip joints, low back, facial joints and other diseases due to its anti-inflammatory activity. It also helps in OA by providing resistance to compression, maintaining the structural integrity, homeostasis, slows breakdown and reduces pain in sore muscles. It is most often used in combination with glucosamine to treat OA. CS is a key role player in the regulation of cell development, cell adhesion, proliferation, and differentiation. Its commercial applications have been continuously explored in the engineering of biological tissues and its combination with other biopolymers to formulate scaffolds which promote and accelerate the regeneration of damaged structure. It is approved in the USA as a dietary supplement for OA, while it is used as a symptomatic slow-acting drug (SYSADOA) in Europe and some other countries. Any significant side effects or overdoses of CS have not been reported in clinical trials suggesting its long-term safety. This review highlights the potential of CS, either alone or in combination with other drugs, to attract the scientists engaged in OA treatment and management across the world.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ogawa H., Hatano S., Sugiura N., Nagai N., Sato T., Shimizu K., Kimata K., Narimatsu H., Watanabe H.: Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin sulfate but not critical for skeletal development. PLoS One. 7(8), e43806 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang G., Ezura Y., Chervoneva I., Robinson P.S., Beason D.P., Carine E.T., Soslowsky L.J., Iozzo R.V., Birk D.E.: Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development. J. Cell. Biochem. 98(6), 1436–1449 (2006)

    Article  CAS  PubMed  Google Scholar 

  3. Atoji Y., Yamamoto Y., Suzuki Y.: The presence of chondroitin sulfate A and C within axon terminals in the Superior olivary nuclei of the adult dog. Neurosci. Lett. 189(1), 39–42 (1995)

    Article  CAS  PubMed  Google Scholar 

  4. Raspanti M., Congiu T., Guizzardi S.: Structural aspects of the extracellular matrix of the tendon: an atomic force and scanning electron microscopy study. Arch. Histol. Cytol. 65(1), 37–43 (2002)

    Article  PubMed  Google Scholar 

  5. Silbert J.E., Sugumaran G.: Biosynthesis of chondroitin/dermatan sulfate. IUBMB life. 54(4), 177–186 (2002)

    Article  CAS  PubMed  Google Scholar 

  6. Kubový P., Mensikova L., Kůrková E., Lopot F., Hojka V., Jelen K.: Influence of SYSADOA group chemicals on progression of human knee joint osteoarthritis: new objective evaluation method-measuring of rheological properties in vivo. Neuro endocrinology letters. 33(6), 651–659 (2011)

    Google Scholar 

  7. Schneider H., Maheu E., Cucherat M.: Symptom-modifying effect of chondroitin sulfate in knee osteoarthritis: a meta-analysis of randomized placebo-controlled trials performed with Structum®. The open rheumatology journal. 6, 183 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Michel B.A., Stucki G., Frey D., De Vathaire F., Vignon E., Bruehlmann P., Uebelhart D.: Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum. 52(3), 779–786 (2005). doi:10.1002/art.20867

    Article  CAS  PubMed  Google Scholar 

  9. Volpi N.: Analytical aspects of pharmaceutical grade chondroitin sulfates. J. Pharm. Sci. 96(12), 3168–3180 (2007)

    Article  CAS  PubMed  Google Scholar 

  10. Rubio-Terrés C.: An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study. Reumatología Clínica. English Edition 6(4), 187–195 (2010)

    Article  PubMed  Google Scholar 

  11. Aubry-Rozier B.: [Role of slow-acting anti-arthritic agents in osteoarthritis (chondroitin sulfate, glucosamine, hyaluronic acid)]. Revue medicale suisse. 8(332), 571–572 (2012)574, 576

    CAS  PubMed  Google Scholar 

  12. Monfort J., Pelletier J.-P., Garcia-Giralt N., Martel-Pelletier J.: Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues. Ann. Rheum. Dis. 67(6), 735–740 (2008)

    Article  CAS  PubMed  Google Scholar 

  13. Uebelhart D.: Clinical review of chondroitin sulfate in osteoarthritis. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 16(Suppl 3), S19–S21 (2008). doi:10.1016/j.joca.2008.06.006

    Article  PubMed  Google Scholar 

  14. Schiraldi C., Cimini D., De Rosa M.: Production of chondroitin sulfate and chondroitin. Appl. Microbiol. Biotechnol. 87(4), 1209–1220 (2010)

    Article  CAS  PubMed  Google Scholar 

  15. Caterson B., Mahmoodian F., Sorrell J.M., Hardingham T., Bayliss M., Carney S., Ratcliffe A., Muir H.: Modulation of native chondroitin sulphate structure in tissue development and in disease. J. Cell Sci. 97(3), 411–417 (1990)

    CAS  PubMed  Google Scholar 

  16. Oryan, A., Moshiri, A., Meimandi-Parizi, A.-H.: Short and long terms healing of the experimentally transverse sectioned tendon in rabbits. BMC Sports Science, Medicine and Rehabilitation 4(1), 14 (2012).

  17. Bobula T., Buffa R., Procházková P., Vágnerová H., Moravcová V., Šuláková R., Židek O., Velebný V.: One-pot synthesis of α, β-unsaturated polyaldehyde of chondroitin sulfate. Carbohydr. Polym. 136, 1002–1009 (2016)

    Article  CAS  PubMed  Google Scholar 

  18. Adebowale A.O., Cox D.S., Liang Z., Eddington N.D.: Analysis of glucosamine and chondroitin sulfate content in marketed products and the Caco-2 permeability of chondroitin sulfate raw materials. J Am Nutraceutical Assoc. 3(1), 37–44 (2000)

    Google Scholar 

  19. Kinoshita-Toyoda A., Yamada S., Haslam S.M., Khoo K.H., Sugiura M., Morris H.R., Dell A., Sugahara K.: Structural determination of five novel tetrasaccharides containing 3-O-sulfated D-glucuronic acid and two rare oligosaccharides containing a beta-D-glucose branch isolated from squid cartilage chondroitin sulfate E. Biochemistry. 43(34), 11063–11074 (2004). doi:10.1021/bi049622d

    Article  CAS  PubMed  Google Scholar 

  20. Caterson B.: Fell-Muir Lecture: chondroitin sulphate glycosaminoglycans: fun for some and confusion for others. Int. J. Exp. Pathol. 93(1), 1–10 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nakano T., Ikawa N., Ozimek L.: An economical method to extract chondroitin sulphate-peptide from bovine nasal cartilage. Can. Agric. Eng. 42(4), 205–208 (2000)

    Google Scholar 

  22. Luo X., Fosmire G., Leach R.: Chicken keel cartilage as a source of chondroitin sulfate. Poult. Sci. 81(7), 1086–1089 (2002)

    Article  CAS  PubMed  Google Scholar 

  23. Nandini C.D., Itoh N., Sugahara K.: Novel 70-kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique heterogenous sulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for growth factors and neurotrophic factors. J. Biol. Chem. 280(6), 4058–4069 (2005)

    Article  CAS  PubMed  Google Scholar 

  24. Lignot B., Lahogue V., Bourseau P.: Enzymatic extraction of chondroitin sulfate from skate cartilage and concentration-desalting by ultrafiltration. J. Biotechnol. 103(3), 281–284 (2003)

    Article  CAS  PubMed  Google Scholar 

  25. Vázquez J.A., Rodríguez-Amado I., Montemayor M.I., Fraguas J., González M.D.P., Murado M.A.: Chondroitin sulfate, hyaluronic acid and chitin/chitosan production using marine waste sources: Characteristics, applications and eco-friendly processes: A review. Marine drugs. 11(3), 747–774 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Lauder R.M.: Chondroitin sulphate: a complex molecule with potential impacts on a wide range of biological systems. Complementary therapies in medicine. 17(1), 56–62 (2009)

    Article  PubMed  Google Scholar 

  27. Tat S.K., Pelletier J.-P., Mineau F., Duval N., Martel-Pelletier J.: Variable effects of 3 different chondroitin sulfate compounds on human osteoarthritic cartilage/chondrocytes: relevance of purity and production process. J. Rheumatol. 37(3), 656–664 (2010)

    Article  CAS  PubMed  Google Scholar 

  28. Calamia V., Lourido L., Fernández-Puente P., Mateos J., Rocha B., Montell E., Vergés J., Ruiz-Romero C., Blanco F.J.: Secretome analysis of chondroitin sulfate-treated chondrocytes reveals anti-angiogenic, anti-inflammatory and anti-catabolic properties. Arthritis research & therapy. 14(5), R202 (2012)

    Article  CAS  Google Scholar 

  29. Guerrini M., Beccati D., Shriver Z., Naggi A., Viswanathan K., Bisio A., Capila I., Lansing J.C., Guglieri S., Fraser B.: Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat. Biotechnol. 26(6), 669–675 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bollet A.J., Nance J.L.: Biochemical findings in normal and osteoarthritic articular cartilage. II. Chondroitin sulfate concentration and chain length, water, and ash content. Journal of Clinical Investigation. 45(7), 1170 (1966)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hascall V.C., Calabro A., Midura R.J., Yanagishita M.: Isolation and characterization of proteoglycans. Methods Enzymol. 230, 390–417 (1993)

    Article  Google Scholar 

  32. Rodén L., Baker J.R., Cifonelli J.A., Mathews M.B.: [7] isolation and characterization of connective tissue polysaccharides. Methods Enzymol. 28, 73–140 (1972)

    Article  Google Scholar 

  33. Kim S.B., Ji C.I., Woo J.W., Do J.R., Cho S.M., Lee Y.B., Kang S.N., Park J.H.: Simplified purification of chondroitin sulphate from scapular cartilage of shortfin mako shark (Isurus oxyrinchus). International Journal of Food Science & Technology. 47(1), 91–99 (2012)

    Article  CAS  Google Scholar 

  34. Bedini E., De Castro C., De Rosa M., Di Nola A., Restaino O.F., Schiraldi C., Parrilli M.: Semi-Synthesis of Unusual chondroitin sulfate polysaccharides containing GlcA (3-O-sulfate) or GlcA (2, 3-di-O-sulfate) Units. Chemistry-A European Journal. 18(7), 2123–2130 (2012)

    Article  CAS  Google Scholar 

  35. Restaino O.F., di Lauro I., Cimini D., Carlino E., De Rosa M., Schiraldi C.: Monosaccharide precursors for boosting chondroitin-like capsular polysaccharide production. Appl. Microbiol. Biotechnol. 97(4), 1699–1709 (2013)

    Article  CAS  PubMed  Google Scholar 

  36. Pomin V.H.: Chondroitin sulfate: Structure, uses and health implications. Nova Science Publishers, Incorporated, Hauppauge (2013)

  37. Liu X., Sun C., Zang H., Wang W., Guo R., Wang F.: Capillary electrophoresis for simultaneous analysis of heparin, chondroitin sulfate and hyaluronic acid and its application in preparations and synovial fluid. J. Chromatogr. Sci. 50(5), 373–379 (2012)

    Article  CAS  PubMed  Google Scholar 

  38. Bielik A.M., Zaia J.: Extraction of chondroitin/dermatan sulfate glycosaminoglycans from connective tissue for mass spectrometric analysis. Methods in molecular biology (Clifton, N.J.). 600, 215–225 (2010). doi:10.1007/978-1-60761-454-8_15

    Article  CAS  Google Scholar 

  39. David J., Roman M., Zhou J., Hildreth J.: Determination of chondroitin sulfate content in raw materials and dietary supplements by high-performance liquid chromatography with ultraviolet detection after enzymatic hydrolysis: Single-laboratory validation. J. AOAC Int. 90(3), 659 (2007)

    Google Scholar 

  40. Solakyildirim K., Zhang Z., Linhardt R.J.: Ultraperformance liquid chromatography with electrospray ionization ion trap mass spectrometry for chondroitin disaccharide analysis. Anal. Biochem. 397(1), 24–28 (2010)

    Article  CAS  PubMed  Google Scholar 

  41. Jackson C.G., Plaas A.H., Sandy J.D., Hua C., Kim-Rolands S., Barnhill J.G., Harris C.L., Clegg D.O.: The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination. Osteoarthr. Cartil. 18(3), 297–302 (2010)

    Article  CAS  PubMed  Google Scholar 

  42. Xiao Y., Li P., Cheng Y., Zhang X., Sheng J., Wang D., Li J., Zhang Q., Zhong C., Cao R.: Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with α-linolenic acid and the transport mechanism of the conjugates. Int. J. Pharm. 465(1), 143–158 (2014)

    Article  CAS  PubMed  Google Scholar 

  43. Ronca G., Conte A.: Metabolic fate of partially depolymerized shark chondroitin sulfate in man. Int. J. Clin. Pharmacol. Res. 13, 27–34 (1992)

    Google Scholar 

  44. Volpi N.: Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Osteoarthr. Cartil. 11(6), 433–441 (2003)

    Article  CAS  PubMed  Google Scholar 

  45. Du J., White N., Eddington N.D.: The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. Biopharm. Drug Dispos. 25(3), 109–116 (2004)

    Article  CAS  PubMed  Google Scholar 

  46. Hathcock J.N., Shao A.: Risk assessment for glucosamine and chondroitin sulfate. Regul. Toxicol. Pharmacol. 47(1), 78–83 (2007)

    Article  CAS  PubMed  Google Scholar 

  47. Cerda C., Bruguera M., Parés A.: Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease. World journal of gastroenterology: WJG. 19(32), 5381 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. von Felden J., Montani M., Kessebohm K., Stickel F.: Drug-induced acute liver injury mimicking autoimmune hepatitis after intake of dietary supplements containing glucosamine and chondroitin sulfate. Int. J. Clin. Pharmacol. Ther. 51(3), 219–223 (2013)

    Article  CAS  Google Scholar 

  49. Felson D.T., Lawrence R.C., Hochberg M.C., McAlindon T., Dieppe P.A., Minor M.A., Blair S.N., Berman B.M., Fries J.F., Weinberger M.: Osteoarthritis: new insights. Part 2: treatment approaches. Annals of internal medicine. 133(9), 726–737 (2000)

    Article  CAS  PubMed  Google Scholar 

  50. Gerlie, C., Koda, R.T., Lien, E.J.: Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey. In: Progress in drug research. pp. 81–103. Springer, (2000)

  51. Zegels B., Crozes P., Uebelhart D., Bruyère O., Reginster J.-Y.: Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study. Osteoarthritis and Cartilage. 21(1), 22–27 (2013)

    Article  CAS  PubMed  Google Scholar 

  52. Uwe S.: Anti-inflammatory interventions of NF-κB signaling: potential applications and risks. Biochem. Pharmacol. 75(8), 1567–1579 (2008)

    Article  CAS  PubMed  Google Scholar 

  53. Foell D., Wittkowski H., Roth J.: Mechanisms of disease: a 'DAMP' view of inflammatory arthritis. Nature clinical practice. Rheumatology. 3(7), 382–390 (2007). doi:10.1038/ncprheum0531

    Article  CAS  PubMed  Google Scholar 

  54. Jomphe C., Gabriac M., Hale T.M., Heroux L., Trudeau L.E., Deblois D., Montell E., Verges J., du Souich P.: Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-kappaB in interleukin-1beta-stimulated chondrocytes. Basic & clinical pharmacology & toxicology. 102(1), 59–65 (2008). doi:10.1111/j.1742-7843.2007.00158.x

    CAS  Google Scholar 

  55. Smiley S.T., King J.A., Hancock W.W.: Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. Journal of immunology (Baltimore, Md.: 1950). 167(5), 2887–2894 (2001)

    Article  CAS  Google Scholar 

  56. Stahel P.F., Smith W.R., Moore E.E.: Role of biological modifiers regulating the immune response after trauma. Injury. 38(12), 1409–1422 (2007). doi:10.1016/j.injury.2007.09.023

    Article  PubMed  Google Scholar 

  57. Liu-Bryan R., Terkeltaub R.: Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous toll-like receptor 2/toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice. Arthritis Rheum. 62(7), 2004–2012 (2010). doi:10.1002/art.27475

    PubMed  PubMed Central  Google Scholar 

  58. van Lent P.L., Blom A.B., Schelbergen R.F., Sloetjes A., Lafeber F.P., Lems W.F., Cats H., Vogl T., Roth J., van den Berg W.B.: Active involvement of alarmins S100 A8 and S100 A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheum. 64(5), 1466–1476 (2012). doi:10.1002/art.34315

    Article  PubMed  CAS  Google Scholar 

  59. Schelbergen R.F., Blom A.B., van den Bosch M.H., Sloetjes A., Abdollahi-Roodsaz S., Schreurs B.W., Mort J.S., Vogl T., Roth J., van den Berg W.B., van Lent P.L.: Alarmins S100 A8 and S100 A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on toll-like receptor 4. Arthritis Rheum. 64(5), 1477–1487 (2012). doi:10.1002/art.33495

    Article  CAS  PubMed  Google Scholar 

  60. Sohn D.H., Sokolove J., Sharpe O., Erhart J.C., Chandra P.E., Lahey L.J., Lindstrom T.M., Hwang I., Boyer K.A., Andriacchi T.P., Robinson W.H.: Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via toll-like receptor 4. Arthritis research & therapy. 14(1), R7 (2012). doi:10.1186/ar3555

    Article  CAS  Google Scholar 

  61. Liu-Bryan R., Pritzker K., Firestein G.S., Terkeltaub R.: TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. Journal of immunology (Baltimore, Md.: 1950). 174(8), 5016–5023 (2005)

    Article  CAS  Google Scholar 

  62. Martinon F., Petrilli V., Mayor A., Tardivel A., Tschopp J.: Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 440(7081), 237–241 (2006). doi:10.1038/nature04516

    Article  CAS  PubMed  Google Scholar 

  63. Pazar B., Ea H.K., Narayan S., Kolly L., Bagnoud N., Chobaz V., Roger T., Liote F., So A., Busso N.: Basic calcium phosphate crystals induce monocyte/macrophage IL-1beta secretion through the NLRP3 inflammasome in vitro. Journal of immunology (Baltimore, Md.: 1950). 186(4), 2495–2502 (2011). doi:10.4049/jimmunol.1001284

    Article  CAS  Google Scholar 

  64. Denoble A.E., Huffman K.M., Stabler T.V., Kelly S.J., Hershfield M.S., McDaniel G.E., Coleman R.E., Kraus V.B.: Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc. Natl. Acad. Sci. U. S. A. 108(5), 2088–2093 (2011). doi:10.1073/pnas.1012743108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Steenvoorden M.M., Bank R.A., Ronday H.K., Toes R.E., Huizinga T.W., DeGroot J.: Fibroblast-like synoviocyte-chondrocyte interaction in cartilage degradation. Clin. Exp. Rheumatol. 25(2), 239–245 (2007)

    CAS  PubMed  Google Scholar 

  66. Wang Q., Rozelle A.L., Lepus C.M., Scanzello C.R., Song J.J., Larsen D.M., Crish J.F., Bebek G., Ritter S.Y., Lindstrom T.M., Hwang I., Wong H.H., Punzi L., Encarnacion A., Shamloo M., Goodman S.B., Wyss-Coray T., Goldring S.R., Banda N.K., Thurman J.M., Gobezie R., Crow M.K., Holers V.M., Lee D.M., Robinson W.H.: Identification of a central role for complement in osteoarthritis. Nat. Med. 17(12), 1674–1679 (2011). doi:10.1038/nm.2543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Loeser R.F.: Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis Rheum. 54(5), 1357–1360 (2006). doi:10.1002/art.21813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kaneko S., Satoh T., Chiba J., Ju C., Inoue K., Kagawa J.: Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines, cellular & molecular therapy. 6(2), 71–79 (2000)

    Article  CAS  Google Scholar 

  69. Martel-Pelletier J., Pelletier J.P., Fahmi H.: Cyclooxygenase-2 and prostaglandins in articular tissues. Semin. Arthritis Rheum. 33(3), 155–167 (2003)

    Article  CAS  PubMed  Google Scholar 

  70. Okamura Y., Watari M., Jerud E.S., Young D.W., Ishizaka S.T., Rose J., Chow J.C., Strauss 3rd J.F.: The extra domain A of fibronectin activates toll-like receptor 4. J. Biol. Chem. 276(13), 10229–10233 (2001). doi:10.1074/jbc.M100099200

    Article  CAS  PubMed  Google Scholar 

  71. Termeer C., Benedix F., Sleeman J., Fieber C., Voith U., Ahrens T., Miyake K., Freudenberg M., Galanos C., Simon J.C.: Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. The Journal of experimental medicine. 195(1), 99–111 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Midwood K., Sacre S., Piccinini A.M., Inglis J., Trebaul A., Chan E., Drexler S., Sofat N., Kashiwagi M., Orend G., Brennan F., Foxwell B.: Tenascin-C is an endogenous activator of toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med. 15(7), 774–780 (2009). doi:10.1038/nm.1987

    Article  CAS  PubMed  Google Scholar 

  73. Nakoshi Y., Hasegawa M., Akeda K., Iino T., Sudo A., Yoshida T., Uchida A.: Distribution and role of tenascin-C in human osteoarthritic cartilage. J. Orthop. Sci. 15(5), 666–673 (2010)

    Article  CAS  PubMed  Google Scholar 

  74. Monfort J., Nacher M., Montell E., Vila J., Verges J., Benito P.: Chondroitin sulfate and hyaluronic acid (500-730 kda) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes. Drugs Exp. Clin. Res. 31(2), 71–76 (2004)

    Google Scholar 

  75. Homandberg G.A., Hui F.: Association of proteoglycan degradation with catabolic cytokine and stromelysin release from cartilage cultured with fibronectin fragments. Arch. Biochem. Biophys. 334(2), 325–331 (1996). doi:10.1006/abbi.1996.0461

    Article  CAS  PubMed  Google Scholar 

  76. Vuolteenaho K., Koskinen A., Kukkonen M., Nieminen R., Päivärinta U., Moilanen T., Moilanen E.: Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage—mediator role of NO in Leptin-Induced P G E. Mediat. Inflamm. 2009, 345838 (2009)

    Article  CAS  Google Scholar 

  77. Ishimaru D., Sugiura N., Akiyama H., Watanabe H., Matsumoto K.: Alterations in the chondroitin sulfate chain in human osteoarthritic cartilage of the knee. Osteoarthr. Cartil. 22(2), 250–258 (2014)

    Article  CAS  PubMed  Google Scholar 

  78. Sokolove J., Lepus C.M.: Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Therapeutic advances in musculoskeletal disease. 5(2), 77–94 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gupta G.S., Gupta A., Gupta R.K.: Animal lectins: form. Function and Clinical Applications, Form, Function and Clinical Applications. Springer, Vienna (2012)

    Book  Google Scholar 

  80. Harris E.N., Weigel P.H.: The ligand-binding profile of HARE: hyaluronan and chondroitin sulfates A, C, and D bind to overlapping sites distinct from the sites for heparin, acetylated low-density lipoprotein, dermatan sulfate, and CS-E. Glycobiology. 18(8), 638–648 (2008). doi:10.1093/glycob/cwn045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Weigel P.H., Yik J.H.: Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochimica et Biophysica Acta (BBA)-General Subjects. 1572(2), 341–363 (2002)

    Article  CAS  Google Scholar 

  82. Dickendesher T.L., Baldwin K.T., Mironova Y.A., Koriyama Y., Raiker S.J., Askew K.L., Wood A., Geoffroy C.G., Zheng B., Liepmann C.D.: NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat. Neurosci. 15(5), 703–712 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. du Souich P.: Absorption, distribution and mechanism of action of SYSADOAS. Pharmacol. Ther. 142(3), 362–374 (2014)

    Article  PubMed  CAS  Google Scholar 

  84. Bara J.J., Johnson W.E.B., Caterson B., Roberts S.: Articular cartilage glycosaminoglycans inhibit the adhesion of endothelial cells. Connect. Tissue Res. 53(3), 220–228 (2012)

    Article  CAS  PubMed  Google Scholar 

  85. Martel-Pelletier J., Roubille C., Abram F., Hochberg M.C., Dorais M., Delorme P., Raynauld J.-P., Pelletier J.-P.: First-line analysis of the effects of treatment on progression of structural changes in knee osteoarthritis over 24 months: data from the osteoarthritis initiative progression cohort. Ann. Rheum. Dis. 74, 547–556 (2015)

    Article  CAS  PubMed  Google Scholar 

  86. Wildi L.M., Raynauld J.-P., Martel-Pelletier J., Beaulieu A., Bessette L., Morin F., Abram F., Dorais M., Pelletier J.-P.: Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann. Rheum. Dis. 70(6), 982–989 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  87. Largo R., Roman-Blas J., Moreno-Rubio J., Sánchez-Pernaute O., Martínez-Calatrava M., Castañeda S., Herrero-Beaumont G.: Chondroitin sulfate improves synovitis in rabbits with chronic antigen-induced arthritis. Osteoarthr. Cartil. 18, S17–S23 (2010)

    Article  PubMed  Google Scholar 

  88. Hochberg M.: Structure-modifying effects of chondroitin sulfate in knee osteoarthritis: an updated meta-analysis of randomized placebo-controlled trials of 2-year duration. Osteoarthr. Cartil. 18, S28–S31 (2010)

    Article  PubMed  Google Scholar 

  89. Hochberg M., Chevalier X., Henrotin Y., Hunter D., Uebelhart D.: Symptom and structure modification in osteoarthritis with pharmaceutical-grade chondroitin sulfate: what's the evidence? Current Medical Research & Opinion. 29(3), 259–267 (2013)

    Article  CAS  Google Scholar 

  90. Imada K., Oka H., Kawasaki D., Miura N., Sato T., Ito A.: Anti-arthritic action mechanisms of natural chondroitin sulfate in human articular chondrocytes and synovial fibroblasts. Biol. Pharm. Bull. 33(3), 410–414 (2010)

    Article  CAS  PubMed  Google Scholar 

  91. Ouzzine M., Venkatesan N., Fournel-Gigleux S.: Proteoglycans and cartilage repair. in: proteoglycans, pp. 339–355. Springer, N. Y. (2012)

    Book  Google Scholar 

  92. Campbell E.J., Owen C.A.: The sulfate groups of chondroitin sulfate-and heparan sulfate-containing proteoglycans in neutrophil plasma membranes are novel binding sites for human leukocyte elastase and cathepsin G. J. Biol. Chem. 282(19), 14645–14654 (2007)

    Article  CAS  PubMed  Google Scholar 

  93. Tat S.K., Pelletier J.-P., Vergés J., Lajeunesse D., Montell E., Fahmi H., Lavigne M., Martel-Pelletier J.: Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: a basic science study. Arthritis Res. Ther. 9(6), R117 (2007)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Sobal G., Dorotka R., Menzel J., Sinzinger H.: Uptake studies with chondrotropic 99mTc-chondroitin sulfate in articular cartilage. Implications for imaging osteoarthritis in the knee. Nucl Med Biol. 40(8), 1013–1017 (2013). doi:10.1016/j.nucmedbio.2013.07.007

    CAS  PubMed  Google Scholar 

  95. Campo G.M., Avenoso A., Campo S., Ferlazzo A., Altavilla D., Micali C., Calatroni A.: Aromatic trap analysis of free radicals production in experimental collagen-induced arthritis in the rat: protective effect of glycosaminoglycans treatment. Free Radic. Res. 37(3), 257–268 (2003)

    Article  CAS  PubMed  Google Scholar 

  96. Martínez-Calatrava M., Largo R., Herrero-Beaumont G.: Improvement of experimental accelerated atherosclerosis by chondroitin sulphate. Osteoarthr. Cartil. 18, S12–S16 (2010)

    Article  PubMed  Google Scholar 

  97. Jain A., Gulbake A., Shilpi S., Jain A., Hurkat P., Jain S.K.: A new horizon in modifications of chitosan: syntheses and applications. Crit. Rev. Ther. Drug Carrier Syst. 30(2), 91–181 (2013)

    Article  CAS  PubMed  Google Scholar 

  98. Subudhi M., Jain A., Jain A., Hurkat P., Shilpi S., Gulbake A., Jain S.: Eudragit S100 Coated Citrus Pectin nanoparticles for Colon targeting of 5-Fluorouracil. Materials. 8(3), 832–849 (2015)

    Article  Google Scholar 

  99. Jain A., Jain S.K.: Environmentally Responsive Chitosan-based Nanocarriers (CBNs). Handbook of Polymers for Pharmaceutical Technologies, Biodegradable Polymers. 3, 105 (2015)

    Article  Google Scholar 

  100. Bauerova K., Ponist S., Kuncirova V., Mihalova D., Paulovicova E., Volpi N.: Chondroitin sulfate effect on induced arthritis in rats. Osteoarthr. Cartil. 19(11), 1373–1379 (2011)

    Article  CAS  PubMed  Google Scholar 

  101. Gabay C., Medinger-Sadowski C., Gascon D., Kolo F., Finckh A.: Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: A randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis & Rheumatism. 63(11), 3383–3391 (2011)

    Article  CAS  Google Scholar 

  102. Nakasone Y., Watabe K., Watanabe K., Tomonaga A., Nagaoka I., Yamamoto T., Yamaguchi H.: Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study. Exp Ther Med. 2(5), 893–899 (2011). doi:10.3892/etm.2011.298

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Chen L., Ling P., Jin Y., Zhang T.: Hyaluronic acid in combination with chondroitin sulfate and hyaluronic acid improved the degeneration of synovium and cartilage equally in rabbits with osteoarthritis. Drug discoveries & therapeutics. 5(4), 190–194 (2011)

    Article  CAS  Google Scholar 

  104. Kanzaki N., Saito K., Maeda A., Kitagawa Y., Kiso Y., Watanabe K., Tomonaga A., Nagaoka I., Yamaguchi H.: Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study. J. Sci. Food Agric. 92(4), 862–869 (2012)

    Article  CAS  PubMed  Google Scholar 

  105. Perea S.: Nutritional management of osteoarthritis. Compendium (Yardley, PA). 34(5), E4 (2012)

    Google Scholar 

  106. Lascelles B., DePuy V., Thomson A., Hansen B., Marcellin-Little D., Biourge V., Bauer J.: Evaluation of a therapeutic diet for feline degenerative joint disease. J. Vet. Intern. Med. 24(3), 487–495 (2010)

    Article  CAS  PubMed  Google Scholar 

  107. DiNubile N.A.: A potential role for Avocado-and Soybean-Based Nutritional supplements in the management of Osteoarthritis. Physician and Sportsmedicine. 38(2), 71–81 (2010)

    Article  PubMed  Google Scholar 

  108. Pavelka K., Coste P., Géher P., Krejci G.: Efficacy and safety of piascledine 300 versus chondroitin sulfate in a 6 months treatment plus 2 months observation in patients with osteoarthritis of the knee. Clin. Rheumatol. 29(6), 659–670 (2010)

    Article  PubMed  Google Scholar 

  109. Richette P.: Management of osteoarthritis: oral therapies. Rev Prat. 62(5), 654–660 (2012)

    PubMed  Google Scholar 

  110. Sofat N., Beith I., Anilkumar P.G., Mitchell P.: Recent clinical evidence for the treatment of osteoarthritis: What we have learned. Reviews on recent clinical trials. 6(2), 114–126 (2011)

    Article  PubMed  Google Scholar 

  111. Diehl P., Gerdesmeyer L., Schauwecker J., Kreuz P., Gollwitzer H., Tischer T.: Conservative therapy of osteoarthritis. Der Orthopade. 42(2), 125–139 (2013)

    Article  CAS  PubMed  Google Scholar 

  112. Railhac J., Zaim M., Saurel A., Vial J., Fournie B.: Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI. Clin. Rheumatol. 31(9), 1347–1357 (2012)

    Article  PubMed  Google Scholar 

  113. Guilherme M.R., Reis A.V., Alves B.R., Kunita M.H., Rubira A.F., Tambourgi E.B.: Smart hollow microspheres of chondroitin sulfate conjugates and magnetite nanoparticles for magnetic vector. J. Colloid Interface Sci. 352(1), 107–113 (2010)

    Article  CAS  PubMed  Google Scholar 

  114. Wang S.-C., Chen B.-H., Wang L.-F., Chen J.-S.: Characterization of chondroitin sulfate and its interpenetrating polymer network hydrogels for sustained-drug release. Int. J. Pharm. 329(1), 103–109 (2007)

    Article  CAS  PubMed  Google Scholar 

  115. Strehin I., Nahas Z., Arora K., Nguyen T., Elisseeff J.: A versatile pH sensitive chondroitin sulfate–PEG tissue adhesive and hydrogel. Biomaterials. 31(10), 2788–2797 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Oprea A.-M., Profire L., Lupusoru C.E., Ghiciuc C.M., Ciolacu D., Vasile C.: Synthesis and characterization of some cellulose/chondroitin sulphate hydrogels and their evaluation as carriers for drug delivery. Carbohydr. Polym. 87(1), 721–729 (2012)

    Article  CAS  Google Scholar 

  117. Li W., Li X., Su H., Zhao S., Li Y., Hu J.: Facile synthesis of chondroitin sulfate-stabilized gold nanoparticles. Mater. Chem. Phys. 125(3), 518–521 (2011)

    Article  CAS  Google Scholar 

  118. Jiang T., Petersen R.R., Call G., Ofek G., Gao J., Yao J.Q.: Development of chondroitin sulfate encapsulated PLGA microsphere delivery systems with controllable multiple burst releases for treating osteoarthritis. Journal of biomedical materials research. Part B, Applied biomaterials. 97(2), 355–363 (2011). doi:10.1002/jbm.b.31822

    Article  PubMed  CAS  Google Scholar 

  119. Craciunescu O., Moldovan L., Moisei M., Trif M.: Liposomal formulation of chondroitin sulfate enhances its antioxidant and anti-inflammatory potential in L929 fibroblast cell line. Journal of liposome research. 23(2), 145–153 (2013)

    Article  CAS  PubMed  Google Scholar 

  120. Bagari R., Bansal D., Gulbake A., Jain A., Soni V., Jain S.K.: Chondroitin sulfate functionalized liposomes for solid tumor targeting. J. Drug Target. 19(4), 251–257 (2011)

    Article  CAS  PubMed  Google Scholar 

  121. Onishi H., Yoshida R., Matsuyama M.: Chondroitin sulfate-glycyl-prednisolone conjugate as arthritis targeting system: localization and drug release in inflammatory joints. Biol. Pharm. Bull. 37(10), 1641–1649 (2014)

    Article  CAS  PubMed  Google Scholar 

  122. Avachat A., Kotwal V.: Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondroitin sulphate. AAPS PharmSciTech. 8(4), 51–56 (2007)

    Article  PubMed Central  Google Scholar 

  123. Huang S.-J., Sun S.-L., Feng T.-H., Sung K.-H., Lui W.-L., Wang L.-F.: Folate-mediated chondroitin sulfate-Pluronic® 127 nanogels as a drug carrier. Eur. J. Pharm. Sci. 38(1), 64–73 (2009)

    Article  CAS  PubMed  Google Scholar 

  124. Lin Y.-J., Liu Y.-S., Yeh H.-H., Cheng T.-L., Wang L.-F.: Self-assembled poly (ε-caprolactone)-g-chondroitin sulfate copolymers as an intracellular doxorubicin delivery carrier against lung cancer cells. Int. J. Nanomedicine. 7, 4169 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Bishnoi M., Jain A., Hurkat P., Jain S.K.: Aceclofenac-loaded chondroitin sulfate conjugated SLNs for effective management of osteoarthritis. J. Drug Target. 22(9), 805–812 (2014)

    Article  CAS  PubMed  Google Scholar 

  126. Lee E.S., Park K.-H., Kang D., Park I.S., Min H.Y., Lee D.H., Kim S., Kim J.H., Na K.: Protein complexed with chondroitin sulfate in poly (lactide- co-glycolide) microspheres. Biomaterials. 28(17), 2754–2762 (2007)

    Article  CAS  PubMed  Google Scholar 

  127. Santo V.E., Duarte A.R.C., Gomes M.E., Mano J.F., Reis R.L.: Hybrid 3D structure of poly (d, l-lactic acid) loaded with chitosan/chondroitin sulfate nanoparticles to be used as carriers for biomacromolecules in tissue engineering. J. Supercrit. Fluids. 54(3), 320–327 (2010)

    Article  CAS  Google Scholar 

  128. Singh, J.A., Noorbaloochi, S., MacDonald, R., Maxwell, L.J.: Chondroitin for osteoarthritis. Cochrane Database Syst. Rev. (2015). doi:10.1002/14651858.CD005614.pub2

  129. Uebelhart D., Malaise M., Marcolongo R., DeVathaire F., Piperno M., Mailleux E., Fioravanti A., Matoso L., Vignon E.: Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthr. Cartil. 12(4), 269–276 (2004)

    Article  PubMed  Google Scholar 

  130. Mazieres B., Combe B., Phan Van A., Tondut J., Grynfeltt M.: Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study. J. Rheumatol. 28(1), 173–181 (2001)

    CAS  PubMed  Google Scholar 

  131. Sorgente N.: Nakamura. R.M: Methods for treating arthritis using collagen type II, glucosamine chondroitin sulfate, and compositions. US 6162787 A (2000)

  132. Nimni M.E.: Method for alleviating arthritis in mammals. US 6372794 B1 (2002)

  133. Derrieu G.: Pougnas. J.L: Chondroitin sulphate and chitosan compositions for treating rheumatic disorders. US 6599888 B1 (2003)

  134. Miyasaka M., Kawashima H.: Persulfated oligosaccharide acting on selectins and chemokine. US 20060211651 A1 (2006)

  135. Aspberg A., Heinegaerd D., Johnson A., Kvist A.: Use of chondroitin sulphate e (cs-e) for the treatment diseases or conditions related to collagen fibril formation. In. Google Patents (2005)

Download references

Acknowledgments

Authors namely AJ and PH are thankful to Council of Scientific and Industrial Research (New Delhi) for providing Senior Research Fellowship.

Author information

Authors and Affiliations

  1. Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, MP, 470 003, India

    Mamta Bishnoi, Ankit Jain, Pooja Hurkat & Sanjay K. Jain

Authors
  1. Mamta Bishnoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ankit Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pooja Hurkat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sanjay K. Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sanjay K. Jain.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest including all financial and non-financial nature.

Author’s contribution

All authors contributed equally for the content and writing of this manuscript. They read and approved the final manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bishnoi, M., Jain, A., Hurkat, P. et al. Chondroitin sulphate: a focus on osteoarthritis. Glycoconj J 33, 693–705 (2016). https://doi.org/10.1007/s10719-016-9665-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-016-9665-3

Keywords

Search

Navigation