Abstract
Evidence that combined glucosamine sulfate and chondroitin sulfate (Gluchon) or isolated glucosamine (Glu) modifies joint damage in osteoarthritis (OA) is still lacking. We studied joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model. Wistar rats were subjected to ACLT of the right knee (OA) or sham operation. Groups received either Glu (500 mg/kg), Gluchon (500 mg/kg glucosamine +400 mg/kg chondroitin) or vehicle (non-treated—NT) per os starting 7 days prior to ACLT until sacrifice at 70 days. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage was assessed using histology and biochemistry as the chondroitin sulfate (CS) content of cartilage by densitometry (microgram per milligram dried cartilage), comparing to standard CS. The molar weight (Mw) of the CS samples, used as a qualitative biochemical parameter, was obtained by comparing their relative mobility on a polyacrylamide gel electrophoresis to standard CS. Gluchon, but not Glu, significantly reduced joint pain (P < 0.05) compared to NT. There was an increase in CS content in the OA group (77.7 ± 8.3 μg/mg) compared to sham (53.5 ± 11.2 μg/mg) (P < 0.05). The CS from OA samples had higher Mw \(\left( {{\text{4}}{\text{.62}} \pm {\text{0}}{\text{.24}} \times {\text{10}}^{\text{4}} \;{{\text{g}} \mathord{\left/ {\vphantom {{\text{g}} {{\text{mol}}}}} \right. \kern-\nulldelimiterspace} {{\text{mol}}}}} \right)\) compared to sham \(\left( {{\text{4}}{\text{.18}} \pm {\text{0}}{\text{.19}} \times {\text{10}}^{\text{4}} {{\text{g}} \mathord{\left/ {\vphantom {{\text{g}} {{\text{mol}}}}} \right. \kern-\nulldelimiterspace} {{\text{mol}}}}} \right)\) (P < 0.05). Gluchon administration significantly reversed both the increases in CS content (54.4 ± 12.1 μg/mg) and Mw \(\left( {{\text{4}}{\text{.18}} \pm {\text{0}}{\text{.2}} \times {\text{10}}^{\text{4}} \,{\text{g/mol}}} \right)\) as compared to NT. Isolated Glu decreased CS content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration. Gluchon provides clinical (analgesia) and structural benefits in the ACLT model. This is the first demonstration that biochemical alterations occurring in parallel to histological damage in OA are prevented by Gluchon administration.
Similar content being viewed by others
References
Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C (2001) Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 357:251–256
Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC (2002) Glucosamine sulphate use and delay of progression of knee osteoarthritis. Arch Intern Med 162:2113–2123
Altman RD (2004) Measurement of structure (disease) modification in osteoarthritis. Osteoarthr Cartil 12(Suppl A):S69–S76
Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2:CD002946
Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araújo D, Figueroa M, Branco J (2007) Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum 56:555–567
Clegg DO, Reda DJ, Harris CL, Klein MA, O’Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ (2006) Glucosamine, chondroitin sulfate and the two in combination for painful knee osteoarthritis. N Engl J Med 354:795–808
McAlindon TE, LaValley MP, Gulin JP, Felson DT (2000) Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 283:1469–1475
Leeb BF, Schwietzer H, Montag K, Smolen JS (2000) A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol 27:205–211
Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY (2003) Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 163:1514–1522
Messier SP, Mihalko S, Loeser RF, Legault C, Jolla J, Pfruender J, Prosser B, Adrian A, Williamson JD (2007) Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthr Cartil 15:1256–1266
Rozendaal RM, Koes BW, van Osch GJ, Uitterlinden EJ, Garling EH, Willemsen SP, Ginai AZ, Verhaar JA, Weinans H, Bierma-Zeinstra SM (2008) Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Ann Intern Med 148:268–277
Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, Bierma-Zienstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil 16:137–162
Lohmander LS, Ostenberg A, Englund M, Roos H (2004) High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. Arthritis Rheum 50:3145–3152
Ameye LG, Young MF (2006) Animal models of osteoarthritis: lessons learned while seeking the “Holy Grail”. Curr Opin Rheumatol 18:537–547
Castro RR, Cunha FQ, Silva Jr FS, Rocha FAC (2006) A quantitative approach to measure joint pain in experimental osteoarthritis—evidence of a role for nitric oxide. Osteoarthr Cartil 14:769–776
Tiraloche G, Girard C, Chouinard L, Sampalis J, Moquin L, Ionescu M, Reiner A, Poole AR, Laverty S (2005) Effect of oral glucosamine on cartilage degradation in a rabbit model of osteoarthritis. Arthritis Rheum 52:1118–1128
Lippiello L, Woodward J, Karpman R, Hammad TA (2000) In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulphate. Clin Orthop 381:229–240
Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB (2006) Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr Cartil 14:13–29
Bezerra MM, Brain SD, Greenacre S, Jerônimo SM, de Melo LB, Keeble J, da Rocha FA (2004) Reactive nitrogen species scavenging, rather than nitric oxide inhibition, protects from articular cartilage damage in rat zymosan-induced arthritis. Br J Pharmacol 141:172–182
Dietrich CP, Dietrich SM (1972) Simple micro method for identification of heparin and other acidific mucopolysaccharides from mammalian tissues. Anal Biochem 46:209–218
Vilensky JA, O’Connor BL, Dunn EA, Rogers PI (1994) Serial analysis of the trunk and limb joints after anterior cruciate ligament transection: temporal, spatial, and angular changes in a canine model of osteoarthritis. J Electromyogr Kinesiol 4:181–192
Andriacchi TP, Birac D (1993) Functional testing in the anterior cruciate ligament-deficient knee. Clin Orthop Relat Res 288:40–47
Tallarida RJ, Cowan A, Raffa RB (2003) Antinociceptive synergy, additivity and subadditivity with combinations of oral glucosamine plus nonopioid analgesics in mice. J Pharmacol Exp Ther 307:699–704
Huebner JL, Seifer DR, Kraus VB (2007) A longitudinal analysis of serum cytokines in the Hartley guinea pig model of osteoarthritis. Osteoarthr Cartil 15:354–356
Custers RJ, Creemers LB, Verbout AJ, van Rijen MH, Dhert WJ, Saris DB (2007) Reliability, reproducibility and variability of the traditional Histologic/Histochemical Grading System vs the new OARSI Osteoarthritis Cartilage Histopathology Assessment System. Osteoarthr Cartil 15:1241–1248
Farndale RW, Sayers CA, Barrett AJ (1982) A direct spectrophotometric microassay for sulphated glycosaminoglycans in cartilage cultures. Connect Tissue Res 9:247–248
Brandt K, Braunstein EM, Visco DM, O’Connor B, Heck D, Albrecht M (1991) Anterior (cranial) cruciate ligament transection in the dog: a bona fide model of osteoarthritis, not merely of cartilage injury and repair. J Rheumatol 18:436–446
Brown MP, Trumble TN, Plaas AH, Sandy JD, Romano M, Hernandez J, Merritt KA (2007) Exercise and injury increase chondroitin sulfate chain length and decrease hyaluronan chain length in synovial fluid. Osteoarthr Cartil 15:1318–1325
Inerot S, Heinegard D, Audell L, Olsson SE (1978) Articular-cartilage proteoglycans in aging and osteoarthritis. Biochem J 169:143–156
Rizkalla G, Reiner A, Bogoch E, Poole AR (1992) Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. J Clin Invest 90:2268–2277
Bollet AJ, Nance JL (1966) Biochemical findings in normal and osteoarthritic articular cartilage. II. Chondroitin sulphate concentration and chain length, water, and ash content. J Clin Invest 45:1170–1177
Aigner T, Mckenna L (2002) Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci 59:5–18
van Osch G, Uitterlinden EJ, Koevoet WLM, DeGroot J, Vefhaar JAN, Weinans H (2006) Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants. Osteoarthr Cartil 14:250–257
Acknowledgments
The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for partial financial support.
Disclosure
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Silva , F.S., Yoshinari, N.H., Castro, R.R. et al. Combined glucosamine and chondroitin sulfate provides functional and structural benefit in the anterior cruciate ligament transection model. Clin Rheumatol 28, 109–117 (2009). https://doi.org/10.1007/s10067-008-0988-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-008-0988-8