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Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture

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Abstract

Osteoarthritis (OA) is a degenerative joint disease that progressively causes a loss of joint functions and the impaired quality of life. The most significant event in OA is a high degree of degradation of articular cartilage accompanied by the loss of chondroitin sulfate-proteoglycans (CS-PGs). Recently, the chondroprotective effects of sesamin, the naturally occurring substance found in sesame seeds, have been proved in a rat model of papain-induced osteoarthritis. We hypothesized that sesamin may be associated with possible promotion of the biosynthesis of CS-PGs in human articular chondrocytes. The aim of the study was to investigate the effects of sesamin on the major CS-PG biosynthesis in primary human chondrocyte. The effects of sesamin on the gene expression of the PG core and the CS biosynthetic enzymes as well as on the secretion of glycosaminoglycans (GAGs) in monolayer and pellet culture systems of articular chondrocytes. Sesamin significantly increased the GAGs content both in culture medium and pellet matrix. Real-time-quantitative PCR showed that sesamin promoted the expression of the genes encoding the core protein (ACAN) of the major CS-PG aggrecan and the biosynthetic enzymes (XYLT1, XYLT2, CHSY1 and CHPF) required for the synthesis of CS-GAG side chains. Safranin-O staining of sesamin treated chondrocyte pellet section confirmed the high degree of GAG accumulation. These results were correlated with an increased level of secreted GAGs in the media of cultured articular chondrocytes in both culture systems. Thus, sesamin would provide a potential therapeutic strategy for treating OA patients.

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References

  1. Krasnokutsky, S., Attur, M., Palmer, G., Samuels, J., Abramson, S.B.: Current concepts in the pathogenesis of osteoarthritis. Osteoarthritis. Cartilage 16(Suppl 3), S1–S3 (2008)

    Article  Google Scholar 

  2. Kapoor, M., Martel-Pelletier, J., Lajeunesse, D., Pelletier, J.P., Fahmi, H.: Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol. 7, 33–42 (2011)

    Article  PubMed  CAS  Google Scholar 

  3. Goldring, M.B., Marcu, K.B.: Cartilage homeostasis in health and rheumatic diseases. Arthritis Res. Ther. 11, 224 (2009)

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Sun, Y., Mauerhan, D.R., Kneisl, J.S., James Norton, H., Zinchenko, N., Ingram, J., et al.: Histological examination of collagen and proteoglycan changes in osteoarthritic menisci. Open Rheumatol. J. 6, 24–32 (2012)

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Baffa, O., Cora, L., Americo, M., Fonseca, P., Oliveira, R., Miranda, J.: Magnetic images of pharmaceutical dosage forms in the human gastrointestinal tract. Conf. Proc. IEEE Eng. Med. Biol. Soc. 7, 7254–7257 (2005)

    PubMed  CAS  Google Scholar 

  6. Colville-Nash, P.R., Willoughby, D.A.: COX-1, COX-2 and articular joint disease: a role for chondroprotective agents. Biorheology 39, 171–179 (2002)

    PubMed  CAS  Google Scholar 

  7. Verbruggen, G.: Chondroprotective drugs in degenerative joint diseases. Rheumatology (Oxford) 45, 129–138 (2006)

    Article  CAS  Google Scholar 

  8. Hochberg, M.C., Dougados, M.: Pharmacological therapy of osteoarthritis. Best Pract. Res. Clin. Rheumatol. 15, 583–593 (2001)

    Article  PubMed  CAS  Google Scholar 

  9. Kubo, M., Ando, K., Mimura, T., Matsusue, Y., Mori, K.: Chondroitin sulfate for the treatment of hip and knee osteoarthritis: current status and future trends. Life Sci. 85, 477–483 (2009)

    Article  PubMed  CAS  Google Scholar 

  10. Kamal-Eldin, A., Moazzami, A., Washi, S.: Sesame seed lignans: potent physiological modulators and possible ingredients in functional foods & nutraceuticals. Recent Pat. Food Nutr. Agric. 3, 17–29 (2010)

    Article  Google Scholar 

  11. Phitak, T., Pothacharoen, P., Settakorn, J., Poompimol, W., Caterson, B., Kongtawelert, P.: Chondroprotective and anti-inflammatory effects of sesamin. Phytochemistry 80, 77–88 (2012)

    Article  PubMed  CAS  Google Scholar 

  12. Miyake, Y., Fukumoto, S., Okada, M., Sakaida, K., Nakamura, Y., Osawa, T.: Antioxidative catechol lignans converted from sesamin and sesaminol triglucoside by culturing with Aspergillus. J. Agric. Food Chem. 53, 22–27 (2005)

    Article  PubMed  CAS  Google Scholar 

  13. Miyawaki, T., Aono, H., Toyoda-Ono, Y., Maeda, H., Kiso, Y., Moriyama, K.: Antihypertensive effects of sesamin in humans. J. Nutr. Sci. Vitaminol (Tokyo). 55(87–91) (2009)

    Google Scholar 

  14. Miyahara, Y., Komiya, T., Katsuzaki, H., Imai, K., Nakagawa, M., Ishi, Y., et al.: Sesamin and episesamin induce apoptosis in human lymphoid leukemia Molt 4B cells. Int. J. Mol. Med. 6, 43–46 (2000)

    PubMed  CAS  Google Scholar 

  15. Yamashita, K., Iizuka, Y., Imai, T., Namiki, M.: Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low alpha-tocopherol diet. Lipids 30, 1019–1028 (1995)

    Article  PubMed  CAS  Google Scholar 

  16. Nakabayashi, A., Kitagawa, Y., Suwa, Y., Akimoto, K., Asami, S., Shimizu, S., et al.: alpha-Tocopherol enhances the hypocholesterolemic action of sesamin in rats. Int. J. Vitam. Nutr. Res. 65, 162–168 (1995)

    PubMed  CAS  Google Scholar 

  17. Sirato-Yasumoto, S., Katsuta, M., Okuyama, Y., Takahashi, Y., Ide, T.: Effect of sesame seeds rich in sesamin and sesamolin on fatty acid oxidation in rat liver. J. Agric. Food Chem. 49, 2647–2651 (2001)

    Article  PubMed  CAS  Google Scholar 

  18. Hou, R.C., Huang, H.M., Tzen, J.T., Jeng, K.C.: Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells. J. Neurosci. Res. 74, 123–133 (2003)

    Article  PubMed  CAS  Google Scholar 

  19. Bulow, H.E., Hobert, O.: The molecular diversity of glycosaminoglycans shapes animal development. Annu. Rev. Cell Dev. Biol. 22, 375–407 (2006)

    Article  PubMed  CAS  Google Scholar 

  20. Hu, G., Codina, M., Fisher, S.: Multiple enhancers associated with ACAN suggest highly redundant transcriptional regulation in cartilage. Matrix Biol. 31, 328–337 (2012)

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Mizumoto, S., Sugahara, K.: Bone and skin disorders caused by a disturbance in the biosynthesis of chondroitin sulfate and dermatan sulfate. In: Karamanos, N. (ed.) Extracellular Matrix Pathology and Signaling. De Gruyter, Berlin (2012)

    Google Scholar 

  22. Mizumoto, S., Ikegawa, S., Sugahara, K.: Human genetic disorders caused by mutations in the genes encoding biosynthetic enzymes for sulfated glycosaminoglycans. J. Biol. Chem. 288, 10953–10961 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Ambrosius, M., Kleesiek, K., Gotting, C.: The xylosyltransferase Iota gene polymorphism c.343G>T (p.A115S) is associated with decreased serum glycosaminoglycan levels. Clin. Biochem. 42, 1–4 (2009)

    Article  PubMed  CAS  Google Scholar 

  24. Cuellar, K., Chuong, H., Hubbell, S.M., Hinsdale, M.E.: Biosynthesis of chondroitin and heparan sulfate in chinese hamster ovary cells depends on xylosyltransferase II. J. Biol. Chem. 282, 5195–5200 (2007)

    Article  PubMed  CAS  Google Scholar 

  25. Kitagawa, H., Izumikawa, T., Uyama, T., Sugahara, K.: Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization. J. Biol. Chem. 278, 23666–23671 (2003)

    Article  PubMed  CAS  Google Scholar 

  26. Kitagawa, H., Uyama, T., Sugahara, K.: Molecular cloning and expression of a human chondroitin synthase. J. Biol. Chem. 276, 38721–38726 (2001)

    Article  PubMed  CAS  Google Scholar 

  27. Nakajima, M., Mizumoto, S., Miyake, N., Kogawa, R., Iida, A., Ito, H., Kitoh, H., Hirayama, A., Mitsubuchi, H., Miyazaki, O., Kosaki, R., Horikawa, R., Lai, A., Mendoza-Londono, R., Dupuis, L., Chitayat, D., Howard, A., Ferraz-Leal, G., Cavalcanti, D., Tsurusaki, Y., Saitsu, H., Watanabe, S., Lausch, E., Unger, S., Bonafe L., Ohashi, H., Superti-Furga, A., Matsumoto, N., Sugahara, K., Nishimura, G., Ikegawa, S.: Mutations in B3GALT6 which encodes a glycosaminoglycan linker region enzyme cause a spectrum of skeletal and connective tissue disorders. Am. J. Human Genetics. 92, 927–934 (2013).

  28. Zimmermann, D.R., Dours-Zimmermann, M.T., Schubert, M., Bruckner-Tuderman, L., Heitz, P.U.: Expression of the extracellular matrix proteoglycan, versican, in human skin. Verh. Dtsch. Ges. Pathol. 78, 481–484 (1994)

    PubMed  CAS  Google Scholar 

  29. Goldring, M.B.: Human chondrocyte cultures as models of cartilage-specific gene regulation. Methods Mol. Med. 107, 69–95 (2005)

    PubMed Central  PubMed  CAS  Google Scholar 

  30. Al-Shanti, N., Saini, A., Stewart, C.E.: Two-step versus one-step RNA-to-CT 2-step and one-step RNA-to-CT 1-step: validity, sensitivity, and efficiency. J. Biomol. Tech. 20, 172–179 (2009)

    PubMed Central  PubMed  Google Scholar 

  31. Zimmermann, D.R., Ruoslahti, E.: Multiple domains of the large fibroblast proteoglycan, versican. EMBO J. 8, 2975–2981 (1989)

    PubMed Central  PubMed  CAS  Google Scholar 

  32. Fidelix, T.S., Soares, B.G., Trevisani, V.F.: Diacerein for osteoarthritis. Cochrane Database Syst Rev. CD005117 (2006).

  33. Hunter, D.J., Wise, B.: Review: diacerein is more effective than placebo and is as effective as NSAIDs for knee and hip osteoarthritis. Evid. Based Med. 12, 74 (2007)

    Article  PubMed  Google Scholar 

  34. Debord, P., Louchahi, K., Tod, M., Cournot, A., Perret, G., Petitjean, O.: Influence of renal function on the pharmacokinetics of diacerein after a single oral dose. Eur. J. Drug Metab. Pharmacokinet. 19, 13–19 (1994)

    Article  PubMed  CAS  Google Scholar 

  35. Pelletier, J.P., Yaron, M., Haraoui, B., Cohen, P., Nahir, M.A., Choquette, D., et al.: Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Arthritis Rheum. 43, 2339–2348 (2000)

    Article  PubMed  CAS  Google Scholar 

  36. Hunter, C.J., Imler, S.M., Malaviya, P., Nerem, R.M., Levenston, M.E.: Mechanical compression alters gene expression and extracellular matrix synthesis by chondrocytes cultured in collagen I gels. Biomaterials 23, 1249–1259 (2002)

    Article  PubMed  CAS  Google Scholar 

  37. Shi, S., Mercer, S., Eckert, G.J., Trippel, S.B.: Regulation of articular chondrocyte aggrecan and collagen gene expression by multiple growth factor gene transfer. J. Orthop. Res. 30, 1026–1031 (2011)

    Article  PubMed  CAS  Google Scholar 

  38. Chung, H.C., Lin, R.C., Logan, G.J., Alexander, I.E., Sachdev, P.S., Sidhu, K.S.: Human induced pluripotent stem cells derived under feeder-free conditions display unique cell cycle and DNA replication gene profiles. Stem Cells Dev. 21, 206–216 (2011)

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Tew, S.R., Pothacharoen, P., Katopodi, T., Hardingham, T.E.: SOX9 transduction increases chondroitin sulfate synthesis in cultured human articular chondrocytes without altering glycosyltransferase and sulfotransferase transcription. Biochem. J. 414, 231–236 (2008)

    Article  PubMed  CAS  Google Scholar 

  40. Prydz, K., Dalen, K.T.: Synthesis and sorting of proteoglycans. J. Cell Sci. 113(Pt 2), 193–205 (2000)

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work described in this paper was supported by Center for Innovation in Chemistry: Postgraduate Education and Research Program in Chemistry (PERCH-CIC), Excellence Center Research Fund, Chiang Mai University and also supported in part by the Japan-Thailand Research Cooperative Program (to K. S. and P. K.) from the Japan Society for the Promotion of Science and the National Research Council of Thailand (JSPS-NRCT).

Author contribution

All authors have participated in the work as following:

PP—drafting of the article, interpretation of the data, final approval of the article, conception and design of the study.

SN—analysis and interpretation of the data, drafting the article, statically analysis.

JS—Histological analysis and interpretation.

SM—drafting of the article, final approval of the article.

KS—final approval of the article, revising for intellectual content, conception and design of the study.

PK—final approval of the article, revising for intellectual content, conception and design of the study.

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Authors and Affiliations

  1. Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Intavaroros Road, Sripoom, Muang, Chiang Mai, 50200, Thailand

    Peraphan Pothacharoen, Sumet Najarus & Prachya Kongtawelert

  2. Department of Pathology, Faculty of Medicine, Chiang Mai University, Intavaroros Road, Sripoom, Chiang Mai, 50200, Thailand

    Jongkolnee Settakorn

  3. Proteoglycan Signaling and Therapeutics Research Group, Faculty of Advanced Life Science, Hokkaido University Graduate School of Life Science, Sapporo, 001-0021, Japan

    Shuji Mizumoto & Kazuyuki Sugahara

  4. Hokkaido University, West-11, North-21, Sapporo, 001-0021, Japan

    Kazuyuki Sugahara

  5. 110 Intavaroros, Amphur Muang, Chiang Mai, 50200, Thailand

    Prachya Kongtawelert

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  1. Peraphan Pothacharoen
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  2. Sumet Najarus
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  3. Jongkolnee Settakorn
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  4. Shuji Mizumoto
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  5. Kazuyuki Sugahara
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  6. Prachya Kongtawelert
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Corresponding authors

Correspondence to Kazuyuki Sugahara or Prachya Kongtawelert.

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Pothacharoen, P., Najarus, S., Settakorn, J. et al. Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture. Glycoconj J 31, 221–230 (2014). https://doi.org/10.1007/s10719-013-9514-6

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  • DOI: https://doi.org/10.1007/s10719-013-9514-6

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