Anat Cell Biol.  2010 Jun;43(2):125-131. 10.5115/acb.2010.43.2.125.

Effects of hyaluronan on carrageenan-induced synovitis in rat TMJ

Affiliations
  • 1Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei Universit

Abstract

Nitric oxide is one of many proinflammatory mediators that are involved in temporomandibular joint (TMJ) inflammatory disorder and is synthesized by inducible nitric oxide synthase (iNOS). iNOS is transcriptionally regulated by nuclear factor-kappaB (NF-kappaB) in cases of inflammation, proliferation, and apoptosis. It has also been reported that nitric oxide is positively regulated by carrageenan and negatively regulated by hyaluronan in the knee joint. The aim of this study was to histologically evaluate how inflammation and cell proliferation of the synovial membrane are affected by the exogenous administration of carrageenan and hyaluronan in the rat TMJ by investigating iNOS, NF-kappaB, and anti proliferating cell nuclear antigen (PCNA) immunoreactivity. As results, immunoreactive cells to iNOS, NF-kappaB, and PCNA were normally localized only in the synovial membrane of wild type TMJs. The numbers of immunoreactive cells were extensively larger in the carrageenan-injected synovial membranes exhibiting excessive folding, and smaller in the hyaluronan-injected synovial membranes showing a few folds. These results indicate that a carrageenan injection induced inflammation and cell proliferation especially in the synovial membrane and that hyaluronan relieved the inflammation by decreasing inflammatory molecules in the synovial membrane.

Keyword

Hyaluronan; Carrageenan; TMJ; iNOS; NF-kappaB

MeSH Terms

Animals
Apoptosis
Carrageenan
Cell Proliferation
Hyaluronic Acid
Inflammation
Knee Joint
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
Proliferating Cell Nuclear Antigen
Rats
Synovial Membrane
Synovitis
Temporomandibular Joint
Carrageenan
Hyaluronic Acid
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
Proliferating Cell Nuclear Antigen

Figure

  • Fig. 1 Inducible nitric oxide synthase (iNOS) immunoreactivity at the synovial membrane. The upper joint cavity (ujc) and lower joint cavity (ljc) are separated by the articular disc (ad). (A and B) Wild type temporomandibular joint (TMJ) shows brown-colored immunoreactive cells at the synovial membrane in the posterior portion of the upper joint cavity. The saline-injected TMJ (Saline) shares the iNOS localization pattern with the wild type TMJ. A small fold is observed in the synovial membrane of the wild type and saline-injected TMJs (black arrow). (C) A large fold (black arrowhead), including many iNOS immunopositive cells is observed in the carrageenan-injected TMJ (Carr). (D) A few small folds (white arrows) are found in the TMJ injected with carrageenan followed by hyaluronan (Carr+Hyal). The number of immunoreactive cells in the fold is less than that of the carrageenan-injected TMJs. Scale bar: 500 µm. con: condyle.

  • Fig. 2 Nuclear factor-κB (NF-κB) immunoreactivity at the synovial membrane. (A and B) Wild type and saline-injected TMJs show a small fold (black arrow) and brown-colored immunoreactive cells at the synovial membrane in the posterior portion of the upper joint cavity. The NF-κB localizing pattern in wild type TMJs is almost the same as that in saline-injected TMJs. (C) A large fold (black arrowhead), including many NF-κB immunopositive cells, can be seen in the carrageenan-injected TMJ (Carr). (D) Three small folds (white arrows) in a TMJ synovial membrane injected with carrageenan and hyaluronan (Carr+Hyal). The number of immunoreactive cells in the fold is less than that of the carrageenan-injected TMJ. Scale bar: 500 µm.

  • Fig. 3 Proliferating cell nuclear antigen (PCNA) immunoreactivity at the synovial membrane of the upper joint cavity. (A~H) PCNA immunopositive cells (black arrows) were detected in the posterior-superior synovial membrane. (C, G) PCNA immunoreactive cells were localized in a large area of the synovial membrane in the carrageenan-injected TMJs (Carr). (D, H) The number of PCNA immunoreactive cells in the TMJ synovial membranes injected with carrageenan and hyaluronan (Carr+Hyal) is less than that of carrageenan-injected TMJs. Scale Bars: 100 µm.


Reference

1. Al-Majed AA, Khattab M, Raza M, Al-Shabanah OA, Mostafa AM. Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: the role of nitric oxide. Inflamm Res. 2003. 52:378–382.
2. Calvert RJ, Reicks M. Alterations in colonic thymidine kinase enzyme activity induced by consumption of various dietary fibres. Proc Soc Exp Biol Med. 1988. 189:45–51.
3. Collantes E, Valle Blázquez M, Mazorra V, Macho A, Aranda E, Muñoz E. Nuclear factor-kappa B activity in T cells from patients with rheumatic diseases: a preliminary report. Ann Rheum Dis. 1998. 57:738–741.
4. Cuzzocrea S, Mazzon E, Calabro G, et al. Inducible nitric oxide synthase-knockout mice exhibit resistance to pleurisy and lung injury caused by carrageenan. Am J Respir Crit Care Med. 2000. 162:1859–1866.
5. Cuzzocrea S, Tan DX, Costantino G, Mazzon E, Caputi AP, Reiter RJ. The protective role of endogenous melatonin in carrageenan-induced pleurisy in the rat. FASEB J. 1999. 13:1930–1938.
6. Díaz-Gallego L, Prieto JG, Coronel P, Gamazo LE, Gimeno M, Alvarez AI. Apoptosis and nitric oxide in an experimental model of osteoarthritis in rabbit after hyaluronic acid treatment. J Orthop Res. 2005. 23:1370–1376.
7. Egan CG, Lockhart JC, Ferrell WR, Day SM, McLean JS. Pathophysiological basis of acute inflammatory hyperaemia in the rat knee: roles of cyclo-oxygenase-1 and -2. J Physiol. 2002. 539(Pt 2):579–587.
8. Farrell AJ. Increased concentration of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic disease. Ann Rheum Dis. 1992. 51:1219–1222.
9. Feldmann M, Andreakos E, Smith C, et al. Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Ann Rheum Dis. 2002. 61:Suppl 2. ii13–ii18.
10. Hansra P, Moran EL, Fornasier VL, Bogoch ER. Carrageenan-induced arthritis in the rat. Inflammation. 2000. 24:141–155.
11. Homma H, Takahasi T, Seki H, Ohtani N, Kondon T, Fukuda M. Immunohistochemical localization of inducible nitric oxide synthase in synovial tissue of human temporomandibular joints with internal derangement. Arch Oral Biol. 2001. 46:93–97.
12. Kishimoto G, Hosomichi J, Muramoto T, Kanno Z, Soma K. Influence of estrogen cycle on temporomandibular joint synovial membrane in rat with deviated mandible. J Med Dent Sci. 2007. 54:79–85.
13. Kopp S, Akerman S, Nilner M. Short-term effects of intra-articular sodium hyaluronate, glucocorticoid and saline injections on rheumatoid arthritis of the temporomandibular joint. J Craniomandib Disord. 1991. 5:231–238.
14. Lawand NB, McNearney T, Westlund KN. Amino acid release into the knee joint: key role in nociception and inflammation. Pain. 2000. 86:69–74.
15. Lundeberg T, Alstergren P, Appelgren A, Appelgren B, Carleson J, Kopp S. A model for experimentally induced temporomadubular joint arthritis in rats: effects of carrageenan on europeptide like immunoreactivity. Neuropeptides. 1996. 30:37–44.
16. Makarov SS. NF-kappa B in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res. 2001. 3:200–206.
17. Min HJ, Lee MJ, Kim JY, et al. Alteration of BMP-4 and Runx2 expression patterns in mouse temporomandibular joint after ovariectomy. Oral Diseases. 2007. 13:220–227.
18. Moncada S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand. 1992. 145:201–227.
19. Nozawa-Inoue K, Amizuka N, Ikeda N, Suzuki A, Kawano Y, Maeda T. Synovial membrane in the temporomandibular joint--its morphology, function and development. Arch Histol Cytol. 2003. 66:289–306.
20. Pelletier JP, Lascau-Coman V, Jovanovic D, et al. Selective inhibition of inducible nitric oxide synthase in experimental osteoarthritis is associated with reduction in tissue levels of catabolic factors. J Rheumatol. 1999. 26:2002–2014.
21. Radhakrishnan R, Moore SA, Sluka KA. Unilateral carrageenan injection into muscle or joint induces chronic bilateral hyperalgesia in rats. Pain. 2003. 104:567–577.
22. Singh R, Ahmed S, Islam N, Goldberg VM, Haqqi TM. Epigallocatechin-3-gallate inhibits interleukin-1beta-induced expression of nitric oxide synthase and production of nitric oxide in human chondrocytes: suppression of nuclear factor kappaB activation by degradation of the inhibitor of nuclear factor kappaB. Arthritis Rheum. 2002. 46:2079–2086.
23. Suzuki J, Na HK, Upham BL, Chang CC, Trosko JE. Lamda-carrageenan-induced inhibition of gap-junctional intercellular communication in rat liver epithelial cells. Nutrition and Cancer. 2000. 36:122–128.
24. Takahashi T, Homma H, Nagai H, et al. Specific expression of inducible nitric oxide synthase in the synovium of the diseased temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003. 95:174–181.
25. Takahashi T, Kondoh T, Kamei K, et al. Elevated levels of nitric oxide in synovial fluid from patients with temporomandibular disorders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996. 82:505–509.
26. Tonussi CR, Ferreira SH. Tumor necrosis factor-alpha mediates carrageenan-induced knee joint incapacitation and also trigger overt ociception in previously inflamed rat knee joints. Pain. 1999. 82:81–87.
27. Tzaribachev N, Fritz J, Horger M. Spectrum of magnetic resonance imaging appearances of juvenile Temporomandibular Joints (TMJ) in non-rheumatic children. Acta Radiologica. 2009. 50:1182–1186.
28. Wilcox DK, Higgins J, Bertram TA. Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia. Laboratory Investigation. 1992. 67:405–411.
29. Yamasaki S, Kawakami A, Nakashima T, et al. Importance of NF-kappaB in rheumatoid synovial tissues: in situ NF-kappaB expression and in vitro study using cultured synovial cells. Ann Rheum Dis. 2001. 60:678–684.
30. Yamaza T, Masuda K, Atsuta I, Nishijima K, Kido MA, Tanaka T. Oxidative stress induced DNA damage in the synovial cells of the temporomandibular joint in the rat. J Dent Res. 2004. 83:619–624.
31. Yamaza T, Masuda KF, Tsukiyama Y, et al. NF-kB activation and iNOS expression in the synovial membrane of rat temporomandibular joints after induced synovitis. J Dent Res. 2003. 82:183–188.
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