In vitro and in vivo anti-inflammatory and tendon-healing effects in Achilles tendinopathy of long-term curcumin delivery using porous microspheres

Sung Eun Kim; Young-Pil Yun; Kyu-Sik Shim; Daniel I. Jeon; Kyeongsoon Park; Hak-Jun Kim

Journal of Industrial and Engineering Chemistry, Vol.58, 123-130, February, 2018

DOI10.1016/j.jiec.2017.09.016 Export Citation

In vitro and in vivo anti-inflammatory and tendon-healing effects in Achilles tendinopathy of long-term curcumin delivery using porous microspheres

Sung Eun Kim, Young-Pil Yun, Kyu-Sik Shim¹, Daniel I. Jeon², Kyeongsoon Park^{3, †}, and Hak-Jun Kim^†

Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical College, Guro Hospital, #80, Guro-dong, Guro-gu, Seoul, 08308, Republic of Korea
¹Department of Biomedical Science, College of Medicine, Korea University, Anam-dong, Seongbuk-gu, 02841, Republic of Korea
²Department of Biological Sciences, Western University, 1151 Richmond St., London, ON, N6A 3K7, Canada
³Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, Anseong-si, Gyeonggi-do, 17546, Republic of Korea

E-mail:,

Achilles tendinopathy is a debilitating musculoskeletal condition that causes significant pain and leads to tendon rupture. Cur/PMSs exerted anti-inflammatory effects on LPS-treated tenocytes in a dose-dependent manner by showing significant decreases in the expression of pro-inflammatory markers such as MMP-3 and MMP-13, COX-2, ADAMTS-5, IL-6, and TNF-α. We demonstrated that local injection of Cur/PMSs markedly suppressed the expression of pro-inflammatory markers in tendon tissue of rats with collagenase-induced Achilles tendinopathy. Cur/PMSs remarkably increased the tensile strength of tendon tissue in a dose-dependent manner. Our findings indicate that Cur/PMSs have great potential for tendon tissue healing and restoration in Achilles tendinopathy.

Keywords:Curcumin;Porous microspheres;Collagenase-induced Achilles tendinopathy;Anti-inflammatory effect;Tendon healing

[References]

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Jagetia GC, Aggarwal BB, J. Clin. Immunol., 27, 19 (2007)
Skommer J, Wlodkowic D, Pelkonen J, Exp. Hematol., 35, 84 (2007)
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Corps AN, Curry VA, Buttle DJ, Hazleman BL, Riley GP, Matrix Biol., 23, 163 (2004)
Thampatty BP, Li H, Im HJ, Wang JH, Gene, 386, 154 (2007)
Tsai WC, Hsu CC, Chang HN, Lin YC, Lin MS, Pang JH, J. Orthop. Res., 28, 487 (2010)
Zhang W, Li X, Franchini MC, Xu K, Locatelli E, Martin RC, Monaco I, Li Y, Cui S, Int. J. Nanomed., 11, 2873 (2016)

[Referenced By]

[1] Sobhani S, Dekker R, Postema K, Dijkstra PU, Scand. J. Med. Sci. Sports, 23, 669 (2013)

[2] Lake JE, Ishikawa SN, Foot Ankle Clin., 14, 663 (2009)

[3] Schulze-Tanzil G, Al-Sadi O, Wiegand E, Ertel W, Busch C, Kohl B, Pufe T, Scand. J. Med. Sci. Sports, 21, 337 (2011)

[4] Kvist M, Sports Med., 18, 173 (1994)

[5] Moore RA, Tramer MR, Carroll D, Wiffen PJ, McQuay HJ, BMJ, 316, 333 (1998)

[6] Astrom M, Westlin N, Acta Orthop. Scand., 63, 631 (1992)

[7] Fredberg U, Stengaard-Pedersen K, Scand. J. Med. Sci. Sports, 18, 3 (2008)

[8] Smidt N, van der Windt DA, Assendelft WJ, Deville WL, Korthals-de Bos IB, Bouter LM, Lancet, 359, 657 (2002)

[9] Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S, Liberati A, O'Connell D, Oxman AD, Phillips B, Schunemann H, Edejer TT, Vist GE, Williams JW, Group GW, BMC Health Serv. Res., 4, 38 (2004)

[10] Brown R, Orchard J, Kinchington M, Hooper A, Nalder G, Br. J. Sports Med., 40, 275 (2006)

[11] de Jonge S, de Vos RJ, Weir A, van Schie HT, Bierma-Zeinstra SM, Verhaar JA, Weinans H, Tol JL, Am. J. Sports Med., 39, 1623 (2011)

[12] Pearson J, Rowlands D, Highet R, J. Sport Rehab., 21, 218 (2012)

[13] Magnussen RA, Dunn WR, Thom AB, Clin. J. Sport Med., 19, 54 (2009)

[14] Willberg L, Sunding K, Ohberg L, Forssblad M, Fahlstrom M, Alfredson H, Knee Surg. Sports Traumatol. Arthrosc., 16, 859 (2008)

[15] Yelland MJ, Sweeting KR, Lyftogt JA, Ng SK, Scuffham PA, Evans KA, Br. J. Sports Med., 45, 421 (2011)

[16] He Y, Yue Y, Zheng X, Zhang K, Chen S, Du Z, Molecules, 20, 9183 (2015)

[17] Chan MM, Biochem. Pharmacol., 49, 1551 (1995)

[18] Brennan P, O'Neill LA, Biochem. Pharmacol., 55, 965 (1998)

[19] Jobin C, Bradham CA, Russo MP, Juma B, Narula AS, Brenner DA, Sartor RB, J. Immunol., 163, 3474 (1999)

[20] Plummer SM, Holloway KA, Manson MM, Munks RJ, Kaptein A, Farrow S, Howells L, Oncogene, 18, 6013 (1999)

[21] Bachmeier BE, Mohrenz IV, Mirisola V, Schleicher E, Romeo F, Hohneke C, Jochum M, Nerlich AG, Pfeffer U, Carcinogenesis, 29, 779 (2008)

[22] Jiang D, Gao P, Lin H, Geng H, Connect. Tissue Res., 57, 20 (2016)

[23] Goel A, Jhurani S, Aggarwal BB, Mol. Nutr. Food Res., 52, 1010 (2008)

[24] Aggarwal BB, Sundaram C, Malani N, Ichikawa H, Adv. Exp. Med. Biol., 595, 1 (2007)

[25] Kim SE, Yun YP, Shim KS, Park K, Choi SW, Suh DH, Colloids Surf. B: Biointerfaces, 122, 457 (2014)

[26] Kim SE, Yun YP, Shim KS, Park K, Choi SW, Shin DH, Suh DH, Colloids Surf. B: Biointerfaces, 134, 453 (2015)

[27] Park JW, Yun YP, Park K, Lee JY, Kim HJ, Kim SE, Song HR, Colloids Surf. B: Biointerfaces, 147, 265 (2016)

[28] Lee JY, Kim SE, Yun YP, Choi SW, Jeon DI, Kim HJ, Park KS, Song HR, J. Ind. Eng. Chem., 52, 277 (2017)

[29] Maffulli N, Wong J, Almekinders LC, Clin. Sports Med., 22, 675 (2003)

[30] Sharma P, Maffulli N, Musculoskelet J, Neuronal Interact., 6, 181 (2006)

[31] Huang TS, Lee SC, Lin JK, Proc. Natl. Acad. Sci. U. S. A., 88, 5292 (1991)

[32] Lao CD, Ruffin MTT, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE, Complement BMC, Altern. Med., 6, 10 (2006)

[33] Choi SW, Yeh YC, Zhang Y, Sung HW, Xia Y, Small, 6, 1492 (2010)

[34] Tsuzaki M, Guyton G, Garrett W, Archambault JM, Herzog W, Almekinders L, Bynum D, Yang X, Banes AJ, J. Orthop. Res., 21, 256 (2003)

[35] John T, Lodka D, Kohl B, Ertel W, Jammrath J, Conrad C, Stoll C, Busch C, Schulze-Tanzil G, J. Orthop. Res., 28, 1071 (2010)

[36] Banji D, Pinnapureddy J, Banji OJ, Saidulu A, Hayath MS, Eur. J. Pharmacol., 668, 293 (2011)

[37] Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A, Biochem. Pharmacol., 73, 1434 (2007)

[38] Mathy-Hartert M, Jacquemond-Collet I, Priem F, Sanchez C, Lambert C, Henrotin Y, Inflamm. Res., 58, 899 (2009)

[39] Aggarwal BB, Harikumar KB, Int. J. Biochem. Cell Biol., 41, 40 (2009)

[40] Jagetia GC, Aggarwal BB, J. Clin. Immunol., 27, 19 (2007)

[41] Skommer J, Wlodkowic D, Pelkonen J, Exp. Hematol., 35, 84 (2007)

[42] Shakibaei M, Schulze-Tanzil G, John T, Mobasheri A, Ann. Anat., 187, 487 (2005)

[43] Shishodia S, Amin HM, Lai R, Aggarwal BB, Biochem. Pharmacol., 70, 700 (2005)

[44] Li L, Aggarwal BB, Shishodia S, Abbruzzese J, Kurzrock R, Cancer, 101, 2351 (2004)

[45] Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A, Shakibaei M, J. Biol. Chem., 286, 28556 (2011)

[46] Blanco-Garcia E, Otero-Espinar FJ, Blanco-Mendez J, Leiro-Vidal JM, Luzardo-Alvarez A, Int. J. Pharm., 518, 86 (2017)

[47] Hast MW, Zuskov A, Soslowsky LJ, Bone Joint Res., 3, 193 (2014)

[48] Dirks RC, Warden SJ, Musculoskelet J, Neuronal Interact., 11, 141 (2011)

[49] Lake SP, Ansorge HL, Soslowsky LJ, Disabil. Rehabil., 30, 1530 (2008)

[50] Lin TW, Cardenas L, Glaser DL, Soslowsky LJ, J. Biomech., 39, 61 (2006)

[51] Torres-Silva R, Lopes-Martins RA, Bjordal JM, Frigo L, Rahouadj R, Arnold G, Leal-Junior EC, Magdalou J, Pallotta R, Marcos RL, Lasers Med. Sci., 30, 1985 (2015)

[52] Corps AN, Harrall RL, Curry VA, Fenwick SA, Hazleman BL, Riley GP, Arthritis Rheum., 46, 3034 (2002)

[53] Corps AN, Curry VA, Buttle DJ, Hazleman BL, Riley GP, Matrix Biol., 23, 163 (2004)

[54] Thampatty BP, Li H, Im HJ, Wang JH, Gene, 386, 154 (2007)

[55] Tsai WC, Hsu CC, Chang HN, Lin YC, Lin MS, Pang JH, J. Orthop. Res., 28, 487 (2010)

[56] Zhang W, Li X, Franchini MC, Xu K, Locatelli E, Martin RC, Monaco I, Li Y, Cui S, Int. J. Nanomed., 11, 2873 (2016)