Abstract
Fucoidan is a sulfated polysaccharide widely distributed in brown seaweed. It exhibits several bioactivities, such as anti-cancer, anti-tumor, anti-microbial, anti-diabetic and anti-oxidant properties. However, the effects of fucoidan in chondrocytes are not well established. Previously, we have reported in vitro and in vivo anti-inflammatory effects of fucoidan. In this study, we evaluated the effects and regulatory mechanism of fucoidan derived from Undaria pinnatifida on the cyclooxygenase-2 (COX-2) and type II collagen in rabbit articular chondrocytes. Using western blotting and alcian blue staining, respectively, fucoidan was shown to induce type II collagen and sulfated proteoglycan in a dose- and time-dependent manner. Moreover, fucoidan inhibited the COX-2 expression in a dose- and time-dependent manner and increased the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and AKT kinases in chondrocytes. The inhibition of p38 and AKT using SB203580 and LY294002, respectively, in the presence of fucoidan decreased the expression of type II collagen. However, ERK inhibition using PD98050 stimulated type II collagen expression. Fucoidan increased COX-2 expression in the presence of inhibitors of ERK, p38, and AKT kinases. These results conclusively suggested that fucoidan regulated type II collagen expression via the p38 and AKT pathways, and COX-2 expression via the p38, ERK and AKT pathways in rabbit articular chondrocytes. Moreover, given its ability to mediate cell differentiation and exert anti-inflammatory activity, fucoidan may represent a potential therapeutic substance for use in inflammatory conditions, including arthritis.
Similar content being viewed by others
Abbreviations
- COX:
-
cyclooxygenase
- DAPI:
-
4’,6-diamidino-2-phenylindole
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- ECM:
-
extracellular matrix
- ERK:
-
extracellular signal-regulated kinase
- FITC:
-
fluorescein isothiocyanate
- JNK:
-
c-Jun N-terminal protein kinase
- MAPKs:
-
mitogen-activated protein kinases
- PBS:
-
phosphate buffered saline
- RIPA:
-
ra-dioimmuno precipitation assay buffer
- TBST:
-
Tris-buffered saline/Tween 20
- TRITC:
-
tetramethyl-rhodamine isothiocyanate.
References
Araki E., Forster C., Dubinsky J.M., Ross M.E. & Iadecola C. 2001. Cyclooxygenase-2 inhibitor ns-398 protects neu-ronal cultures from lipopolysaccharide-induced neurotoxicity. Stroke 32: 2370–2375.
Bobacz K., Erlacher L., Smolen J., Soleiman A. & Graninger W.B. 2004. Chondrocyte number and proteoglycan synthesis in the aging and osteoarthritic human articular cartilage. Ann. Rheum. Dis. 63: 1618–1622.
Burrage P.S., Mix K.S. & Brinckerhoff C.E. 2006. Matrix metal-loproteinases: role in arthritis. Front. Biosci. 11: 529–543.
Cho Y.S., Jung W.K., Kim J.A., Choi I.W. & Kim S.K. 2009. Beneficial effects of fucoidan on osteoblastic MG-63 cell differentiation. Food Chem. 116: 990–994.
Chung H.J., Jeun J., Houng S.J., Jun H.J., Kweon D.K. & Lee S.J. 2010. Toxicological evaluation of fucoidan from Undaria pinnatifida in vitro and in vivo. Phytother. Res. 24: 1078–1083.
Cumashi A., Ushakova N.A., Preobrazhenskaya M.E., D’Incecco A., Piccoli A., Totani L., Tinari N., Morozevich G.E., Berman A.E., Bilan M.I. & Usov A.I. 2007. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and an-tiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology 17: 541–552.
Eo S.H., Cho H.S. & Kim S.J. 2014. Resveratrol regulates type II collagen and COX-2 expression via the ERK, p38 and Akt signaling pathways in rabbit articular chondrocytes. Exp. Ther. Med. 7: 640–648.
Grzanna R., Lindmark L. & Frondoza C.G. 2005. Ginger–an herbal medicinal product with broad anti-inflammatory actions. J. Med. Food 8: 125–132.
Han Y. & Kim S.J. 2016. Simvastatin induces differentiation of rabbit articular chondrocytes via the ERK-1/2 and p38 ki-nase pathways. Exp. Cell Res. 346: 198–205.
Heijink A., Gomoll A.H., Madry H., Drobnič M., Filardo G., Espregueira-Mendes J. & Van Dijk C.N. 2012. Biomechan-ical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20: 423–435.
Hemmingson J.A., Falshaw R., Furneaux R.H. & Thompson K. 2006. Structure and antiviral activity of the galactofucan sul-fates extracted from Undaria pinnatifida (Phaeophyta). J. Appl. Phycol. 18: 185–193.
Hillen J., Geyer C., Heitzmann M., Beckmann D., Krause A., Winkler I., Pavenstadt H., Bremer C., Pap T. & Korb-Pap A. 2017. Structural cartilage damage attracts circulating rheumatoid arthritis synovial fibroblasts into affected joints. Arthritis Res. Ther. 19: 40.
Hunziker E.B., Quinn T.M. & Hauselmann H.J. 2002. Quantitative structural organization of normal adult human articular cartilage. Osteoarthr. Cartil. 10: 564–572.
Iovu M., Dumais G. & Du Souich P. 2008. Anti-inflammatory activity of chondroitin sulfate. Osteoarthr. Cartil. 16: S14–S18.
Islander U., Jochems C., Lagerquist M.K., Forsblad-d’Elia H. & Carlsten H. 2011. Estrogens in rheumatoid arthritis; the immune system and bone. Mol. Cell. Endocrinol. 335: 14–29.
Karunanithi P., Murali M.R., Samuel S., Raghavendran H.R.B., Abbas A.A. & Kamarul T. 2016. Three dimensional alginate-fucoidan composite hydrogel augments the chondrogenic differentiation of mesenchymal stromal cells. Carbohydr. Polym. 147: 294–303.
Kim S.J., Ju J.W., Oh C.D., Yoon Y.M., Song W.K., Kim J.H., Yoo Y.J., Bang O.S., Kang S.S. & Chun J.S. 2002. ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J. Biol. Chem. 277: 1332–1339.
Kim B.S., Kang H.J., Park J.Y. & Lee J. 2015. Fucoidan promotes osteoblast differentiation via JNK-and ERK-dependent BMP2-Smad 1/5/8 signaling in human mesenchymal stem cells. Exp. Mol. Med. 47: e128.
Kim D., Choi B., Song J., Kim S., Oh S., Jin E.H., Kang S.S. & Jin E.J. 2011. TiO2 nanotube stimulate chondrogenic differentiation of limb mesenchymal cells by modulating focal activity. Exp. Mol. Med. 43: 455–461.
Lee S.H., Ko C.I., Jee Y., Jeong Y., Kim M., Kim J.S. & Jeon Y.J. 2013. Anti-inflammatory effect of fucoidan extracted from Ecklonia cava in zebrafish model. Carbohydr. Polym. 92: 84–89.
Lefebvre V. 2014. SP0073 Molecular control of cell fate determination in cartilage and joint development. Ann. Rheum. Dis. 73: 20.
Ma B., Leijten J.C.H., Wu L., Kip M., van Blitterswijk C.A., Post J.N. & Karperien M. 2013. Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture. Osteoarthr. Cartil. 21: 599–603.
Maneix L., Servent A., Porée B., Ollitrault D., Branly T., Bigot N., Boujrad N., Flouriot G., Demoor M., Boumediene K. & Moslemi S. 2014. Up-regulation of type II collagen gene by 17β-estradiol in articular chondrocytes involves Sp1/3, Sox-9, and estrogen receptor α. J. Mol. Med. 92: 1179–1200.
Nile S.H., Ko E.Y., Kim D.H. & Keum Y.S. 2016. Screening of ferulic acid related compounds as inhibitors of xanthine ox-idase and cyclooxygenase-2 with anti-inflammatory activity. Rev. Bras. Farmacogn. 26: 50–55.
Osaki T., Kitahara K., Okamoto Y., Imagawa T., Tsuka T., Miki Y., Kawamoto H., Saimoto H. & Minami S. 2012. Effect of fu-coidan extracted from mozuku on experimental cartilaginous tissue injury. Mar. Drugs 10: 2560–2570.
Pap T. & Korb-Pap A. 2015. Cartilage damage in osteoarthritis and rheumatoid arthritis–two unequal siblings. Nat. Rev. Rheumatol. 11: 606–615.
Park S.B., Chun K.R., Kim J.K., Suk K., Jung Y.M. & Lee W.H. 2010. The differential effect of high and low molecular weight fucoidans on the severity of collagen-induced arthritis in mice. Phytother. Res. 24: 1384–1391.
Park S.J., Lee K.W., Lim D.S. & Lee S. 2011. The sulfated polysaccharide fucoidan stimulates osteogenic differentiation of human adipose-derived stem cells. Stem Cells Dev. 21: 2204–2211.
Phull A.R., Eo S.H., Abbas Q., Ahmed M. & Kim S.J. 2016. Applications of chondrocyte-based cartilage engineering: an overview. BioMed Res. Int. 2016: 1879837.
Phull A.R., Eo S.H. & Kim S.J. 2017a. Oleanolic acid (OA) regulates inflammation and cellular dedifferentiation of chondro-cytes via MAPK signaling pathways. Cell. Mol. Biol. (Noisy-le-Grand) 63: 12–17.
Phull A.R. & Kim S.J. 2017. Fucoidan as bio-functional molecule: Insights into the anti-inflammatory potential and associated molecular mechanisms. J. Funct. Foods 38: 415–426.
Phull A.R., Majid M., Haq I.U., Khan M.R. & Kim S.J. 2017b. In vitro and in vivo evaluation of anti-arthritic, antioxidant efficacy of fucoidan from Undaria pinnatifida (Harvey) Suringar. Int. J. Biol. Macromol. 97: 468–480.
Poole A.R., Kobayashi M., Yasuda T., Laverty S., Mwale F., Kojima T., Sakai T., Wahl C., El-Maadawy S., Webb G. & Tchetina E. 2002. Type II collagen degradation and its regulation in articular cartilage in osteoarthritis. Ann. Rheum. Dis. 61: ii78–ii81.
Rainsford K.D. 2007. Anti-inflammatory drugs in the 21st century, pp. 3–27. In: Harris R.E. (ed.) Inflammation in the Pathogenesis of Chronic Diseases. Springer.
Yang C., Chung D., Shin I.S., Lee H., Kim J., Lee Y. & You S. 2008. Effects of molecular weight and hydrolysis conditions on anticancer activity of fucoidans from sporophyll of Undaria pinnatifida. Int. J. Biol. Macromol. 43: 433–437.
Yoo Y.C., Kim W.J., Kim S.Y., Kim S.M., Chung M.K., Park J.W., Suh H.H., Lee K.B. & Park Y.I. 2007. Immunomod-ulating activity of a fucoidan isolated from Korean Undaria pinnatifida sporophyll. Algae 22: 333–338.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Phull, A.R., Kim, S.J. Fucoidan from Undaria pinnatifida regulates type II collagen and COX-2 expression via MAPK and PI3K pathways in rabbit articular chondrocytes. Biologia 72, 1362–1369 (2017). https://doi.org/10.1515/biolog-2017-0158
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1515/biolog-2017-0158