2019 ; Vol.29-2: 297~303
|Author||Jong-Hun Ji, Young-Yul Kim, Kaushal Patel, Namjoon Cho, Sang-Eun Park, Myung-Sup Ko, Suk-Jae Park, Jong Ok Kim|
|Place of duty||Department of Orthopaedic Surgery, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea|
|Title||Dexamethasone Facilitates NF-κB Signal Pathway in TNF-α Stimulated Rotator Cuff Tenocytes|
J. Microbiol. Biotechnol.2019 ;
|Abstract||Corticosteroids are commonly used for pain control in rotator cuff tear. Deregulated NF-κB
activation is a hallmark of chronic inflammatory diseases and has been responsible for the
pathogenesis of rotator cuff tear. The Dexamethasone(DEXA) is a synthetic corticosteroid. The
purpose of this study was to examine the exact effect of dexamethasone on NF-κB signaling in
rotator cuff tear. We measured NF-κB expression in four groups: control, TNF-α-treated,
DEXA-treated, and combined treatment with TNF-α and DEXA. Tenocytes were isolated from
patients with rotator cuff tears and pre-incubated with TNF-α (10 ng/ml), DEXA (1 μM), or
both of them for 10 min, 1 h, and 2 h. Expression of p65, p50, and p52 in the nuclei and cytosol
was analyzed by western blotting and immunofluorescence imaging using confocal
microscopy. We also evaluated nucleus/cytosol (N/C) ratios of p65, p50, and p52. In our
study, the combined treatment with DEXA and TNF-α showed increased N/C ratios of p65,
p50, and p52 compared with those in the TNF-α group at all time points. Additionally, in the
DEXA group, N/C ratios of p65, p50, and p52 gradually increased from 10 min to 2 h. In
conclusion, DEXA promoted the nuclear localization of p65, p50, and p52, but was not
effective in inhibiting the inflammatory response of TNF-α-stimulated rotator cuff tear.|
|Key_word||Rotator cuff, tenocytes, NF-kappa B, glucocorticoid, tumor necrosis factor-alpha|
Dean B J, Lostis E, Oakley T, Rombach I, Morrey ME, Carr AJ. 2014. The risks and benefits of glucocorticoid treatment for tendinopathy: a systematic review of the effects of local glucocorticoid on tendon. Semin. Arthritis Rheum. 43: 570-576.
Coombes BK, Bisset L, Vicenzino B. 2010. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet 376: 1751-1767.
Hart L. 2011. Corticosteroid and other injections in the management of tendinopathies: a review. Clin. J. Sport Med. 21: 540-541.
Koester MC, Dunn WR, Kuhn JE, Spindler KP. 2007. The efficacy of subacromial corticosteroid injection in the treatment of rotator cuff disease: A systematic review. J. Am. Acad. Orthop. Surg. 15: 3-11.
Coombes BK, Bisset L, Brooks P, Khan A, Vicenzino B. 2013. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA 309:461-469.
Yamazaki H, Ochiai N, Kenmoku T, Ohtori S, Sasho T, Miyagi M, et al. 2014. Assessment of pain-related behavior and pro-inflammatory cytokine levels in the rat rotator cuff tear model. J. Orthop. Res. 32: 286-290.
Orita S, Koshi T, Mitsuka T, Miyagi M, Inoue G, Arai G, et al. 2011. Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and painrelated scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet. Disord. 12: 144.
Panzer S, Madden M, Matsuki K. 1993. Interaction of IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in human T cells activated by murine antigens. Clin. Exp. Immunol. 93: 471-478.
Sun SC, Chang JH, Jin J. 2013. Regulation of nuclear factorkappaB in autoimmunity. Trends Immunol. 34: 282-289.
Sun SC. 2011. Non-canonical NF-kappaB signaling pathway. Cell Res. 21: 71-85.
Auwardt R B, Mudge SJ, Chen CG, Power D A. 1 998. Regulation of nuclear factor kappaB by corticosteroids in rat mesangial cells. J. Am. Soc. Nephrol. 9: 1620-1628.
Hugate R, Pennypacker J, Saunders M, Juliano P. 2004. The effects of intratendinous and retrocalcaneal intrabursal injections of corticosteroid on the biomechanical properties of rabbit Achilles tendons. J. Bone Joint Surg. Am. 86-a: 794-801.
Gumina S, Natalizi S, Melaragni F , Leopizzi M, Carbone S , Postacchini F, et al. 2013. The possible role of the transcription factor nuclear factor-kappaB on evolution of rotator cuff tear and on mechanisms of cuff tendon healing. J. Shoulder Elbow Surg. 22: 673-680.
Jo CH, Lee SY, Yoon KS, Shin S. 2017. Effects of platelet-rich plasma with concomitant use of a corticosteroid on tenocytes from degenerative rotator cuff tears in interleukin 1beta-induced tendinopathic conditions. Am. J. Sports Med. 45: 1141-1150.
Mohamadi A, Chan JJ, Claessen FM, Ring D, Chen NC. 2017. Corticosteroid Injections Give Small and Transient Pain Relief in Rotator Cuff Tendinosis: A Meta-analysis. Clin. Orthop. Relat. Res. 475: 232-243.
Riley G. 2008. Tendinopathy-from basic science to treatment. Nat. Clin. Pract. Rheumatol. 4: 82-89.
Tempfer H, Gehwolf R , Lehner C, Wagner A, Mtsariashvili M, Bauer HC, et al. 2009. Effects of crystalline glucocorticoid triamcinolone acetonide on cultered human supraspinatus tendon cells. Acta Orthop. 80: 357-362.
Stannard JP, Bucknell AL. 1993. Rupture of the triceps tendon associated with steroid injections. Am. J. Sports Med. 21: 482-485.
Dean BJ, Franklin SL, Murphy RJ, Javaid MK, Carr AJ. 2014. Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy? Br. J. Sports Med. 48: 1620-1626.
Haraldsson BT, Langberg H, Aagaard P, Zuurmond AM, van El B, Degroot J, et al. 2006. Corticosteroids reduce the tensile strength of isolated collagen fascicles. Am. J. Sports Med. 34: 1992-1997.
Nakamura H, Gotoh M, Kanazawa T, Ohta K, Nakamura K, Honda H, et al. 2015. Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats. J. Orthop. Res. 33: 1523-1530.
Maman E , Yehuda C, Pritsch T , Morag G , Brosh T , Sharfman Z, et al. 2016. Detrimental effect of repeated and single subacromial corticosteroid injections on the intact and injured rotator cuff: a biomechanical and imaging study in rats. Am. J. Sports Med. 44: 177-182.
Mikolyzk D K, Wei A S, Tonino P, Marra G , W illiams D A, Himes RD, et al. 2009. Effect of corticosteroids on the biomechanical strength of rat rotator cuff tendon. J. Bone Joint Surg. Am. 91: 1172-1180.
Ramirez JP, Bonati-Richardson F, Garcia MP, Hidalgo C, Stoore C, Liendo R, et al. 2018. Intra-articular treatment with corticosteroids increases apoptosis in human rotator cuff tears. Connect. Tissue Res. 1-8.
Fry CS, Nayeem SZ, Dillon EL, Sarkar PS, Tumurbaatar B, Urban RJ, et al. 2016. Glucocorticoids increase skeletal muscle NF-kappaB inducing kinase (NIK): links to muscle atrophy. Physiol. Rep. 4pii: e13014.
Dakin SG, Martinez FO, Yapp C, Wells G, Oppermann U, Dean BJ, et al. 2015. Inflammation activation and resolution in human tendon disease. Sci. Trans. Med. 7: 311ra173.
Oh IS, Park SE, Son J M, Chung J Y, Kim Y Y. 2 010. Glucocorticoid mechanism of inhibition of the inflammatory cells in lumbar intervertebral disc cells stimulated by TNF-α production of nuclear factor-α B. J. Korean Orthop. Res. Soc. 13: 80-87.
Moreno R, Sobotzik JM, Schultz C, Schmitz ML. 2010. Specification of the NF-kappaB transcriptional response by p65 phosphorylation and TNF-induced nuclear translocation of IKK epsilon. Nucleic Acids Res. 38: 6029-6044.
Poulsen RC, Carr AJ, Hulley PA. 2011. Protection against glucocorticoid-induced damage in human tenocytes by modulation of ERK, Akt, and forkhead signaling. Endocrinology 152: 503-514.
Wong MW, Tang YY, Lee SK, Fu BS, Chan BP, Chan CK. 2003. Effect of dexamethasone on cultured human tenocytes and its reversibility by platelet-derived growth factor. J. Bone Joint Surg. Am. 85: 1914-1920.
Zhang J, Keenan C, Wang JH. 2013. The effects of dexamethasone on human patellar tendon stem cells:implications for dexamethasone treatment of tendon injury. J. Orthop. Res. 31: 105-110.