Effects of tumor necrosis factor alpha antagonist on the morphological change of Achilles tendon contracture induced by stress shielding

doi:10.3969/j.issn.2095-4344.2013.50.007

Abstract

Abstract:

BACKGROUND: Stress shielding in the Achilles tendons induces over-expression of tumor necrosis factor-α. The degree of tendon contracture remains unclear after the intervention with tumor necrosis factor inhibitor.
OBJECTIVE: To investigate the effects of tumor necrosis factor-α on tendon contracture and the preventive effects of tumor necrosis factor inhibitor (etanercept) on tendon contracture by observing the morphological changes of the stress-shielded Achilles tendons after the intervention with etanercept.
METHODS: A total of 20 healthy male Sprague-Dawley rats were randomly divided into experimental and model groups after stress shielding in Achilles tendons of rat left hind limb. Five rats from either group were randomly selected, and their right hind limbs were considered as normal controls. Immediately after model induction, the rats in the experimental group were subjected with 0.6 mg/kg etanercept, and those in the model group were subcutaneously treated with 1 mL phosphate buffered saline. According to half-life of etanercept, the two groups were separately injected three times. At 2 weeks after intervention, the morphological changes of the Achilles tendons were observed using gross examination and transmission electron microscope.
RESULTS AND CONCLUSION: On gross examination, the Achilles tendons in the experimental group were significantly smoother and smaller than those of the model groups, but thicker than those of the normal control group. Under a transmission electron microscope, the collagen fibrils of the model group were looser and more disordered than those of the experimental group. The collagen fibrils of the experimental group were similar to those of the normal control group in cross section and longitudinal section. These indicated that tumor necrosis factor-α antagonist can obviously prevent stress shielding-induced tendon contracture at 2 weeks.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: tendinopathy, Achilles tendon, contracture, tumor necrosis factor-alpha, recombinant fusion proteins, stress, mechanical

CLC Number:

R318

Li Ping, Zhao Hua-kun, Ma Yan-hong. Effects of tumor necrosis factor alpha antagonist on the morphological change of Achilles tendon contracture induced by stress shielding[J]. Chinese Journal of Tissue Engineering Research, doi: 10.3969/j.issn.2095-4344.2013.50.007.

Figures/Tables 5

References

[1] Hosaka YZ, Uratsuji T, Ueda H, et al. Comparative study of the properties of tendinocytes derived from three different sites in the equine superficial digital flexor tendon. Biomed Res. 2010;31(1):35-44.

[2] Uchida H, Tohyama H, Nagashima K, et al. Stress deprivation simultaneously induces over-expression of interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta in fibroblasts and mechanical deterioration of the tissue in the patellar tendon. J Biomech. 2005;38(4):791-798.

[3] Knobloch K. Comment on: Monitoring Achilles enthesitis in ankylosing spondylitis during TNF-alpha antagonist therapy: an ultrasound study. Rheumatology (Oxford). 2010;49(7): 1418-1419.

[4] Smolen JS, Nash P, Durez P, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet. 2013; 381(9870):918-929.

[5] Chang B, Park HY, Jeon K, et al. Interferon-γ release assay in the diagnosis of latent tuberculosis infection in arthritis patients treated with tumor necrosis factor antagonists in Korea. Clin Rheumatol. 2011;30(12):1535-1541.

[6] Jung YS, Park W, Na K. Temperature-modulated noncovalent interaction controllable complex for the long-term delivery of etanercept to treat rheumatoid arthritis. J Control Release. 2013;171(2):143-151.

[7] Tanida A, Kishimoto Y, Okano T, et al. Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis. Yonago Acta Med. 2013; 56(1):13-19.

[8] Martínez-Santana V, González-Sarmiento E, Calleja-Hernández M, et al. Comparison of drug survival rates for tumor necrosis factor antagonists in rheumatoid arthritis. Patient Prefer Adherence. 2013;7:719-727.

[9] The Ministry of Science and Technology of the people Republic of China.Guidance Suggestions for the Care and Use of Laboratory Animals.2006-09-30.

中华人民共和国科学技术部. 关于善待实验动物的指导性意见. 2006-09-30.

[10] Cui Q,Wang Z, Jiang D,et al. HGF inhibits TGF-β1-induced myofibrobroblast differentiation and EMG deposition via MMP-2 in Achilles tendon in rat. Eur J Appl Physiol.2011; 111(7):1457-1463.

[11] 王伟,马燕红.大鼠跟腱应力屏蔽挛缩模型的建立[J].中国康复理论与实践,2009:15(6):521-523．

[12] 晏小艳,马燕红.IL-1受体拮抗剂干预跟腱挛缩的实验研究[J]．中国康复,2011,26(4):25-28．

[13] Palmes D, Spiegel HU, Schneider TO,et al. Achilles tendon healing:Long-term biomechanical in a new mouse model.J Orthop Res.2002;20(5):939-946.

[14] Ricco S, Renzi S, Del Bue M, et al. logeneic adipose tissue-derived mesenchymal stem cells in combination with platelet rich plasma are safe and effective in the therapy of superficial digital flexor tendonitis in the horse. Int J Immunopathol Pharmacol. 2013;26(1 Suppl):61-68.

[15] Noh MK, Jung M, Kim SH, et al. Assessment of IL-6, IL-8 and TNF-α levels in the gingival tissue of patients with periodontitis. Exp Ther Med. 2013;6(3):847-851.

[16] Rich T, Henderson LB, Becker DL, et al. Indicators of replicative damage in equine tendon fibroblast monolayers. BMC Vet Res. 2013;9(1):180.

[17] Schulze-Tanzil G, Al-Sadi O, Wiegand E, et al. The role of pro-inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights. Scand J Med Sci Sports. 2011;21(3):337-351.

[18] de Araújo RF Júnior, Souza TO, de Moura LM, et al. Atorvastatin Decreases Bone Loss, Inflammation and Oxidative Stress in Experimental Periodontitis. PLoS One. 2013;8(10):e75322.

[19] Akhter N, Nix M, Abdul Y, et al. Delta-Opioid Receptors Attenuate TNF-α-Induced MMP-2 Secretion From Human ONH Astrocytes. Invest Ophthalmol Vis Sci. 2013;54(10): 6605-6611.

[20] Tsuzaki M, Guyton G, Garrett W, et al．IL-1 beta induces COX2, MMP-1, -3 and-13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells．J Orthop Res.2003;21(2):256-264．

[21] Li XM, Dong L, Shi HT, et al. Effect of neferine on hepatic stellate cells in collagen-I, TIMP-1 and MMP-2. Zhongguo Zhong Yao Za Zhi. 2013;38(13):2206-2209.

[22] Ji Y, Wang T, Wei ZF, et al. Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type I collagen. J Ethnopharmacol. 2013; 149(3):825-832.

[23] Furtwängler T, Chan SC, Bahrenberg G, et al. Assessment of the Matrix Degenerative Effects of MMP-3, ADAMTS-4, and HTRA1, Injected Into a Bovine Intervertebral Disc Organ Culture Model. Spine (Phila Pa 1976). 2013;38(22): E1377-1387.

[24] Thornton GM, Shao X, Chung M,et al. Changes in meehanical loading lead to tendon-specific alterations in MMP and TIMP expression：Influence of stress-deprivation and intermittent cyclic hydrostatic compression on rat supraspinatus and Achilles tendons．Br J Sports Med. 2010; 44(10)698-703．

[25] Kameda H. Etanercept. Nihon Rinsho. 2013;71(7): 1214-1217.

[26] Horii M, Orita S, Nagata M,et al., Direct application of the tumor necrosis factor-alpha inhibitor, etanercept, into a punctured intervertebral disc decreases calcitonin gene-related peptide expression in rat dorsal root ganglion neurons. Spine (Phila Pa 1976). 2011;36(2):E80-85.

[27] Rolle AS, Zimmermann B, Poon SH. Etanercept-induced Henoch-Schönlein purpura in a patient with ankylosing spondylitis. J Clin Rheumatol. 2013 ;19(2):90-93.

[28] Zitelli KB, Zedek D, Ranganathan P, et al. Squamous cell carcinoma of the lip associated with adalimumab therapy for ankylosing spondylitis: a case report and review of TNF-α inhibitors and cutaneous carcinoma risk. Cutis. 2013;92(1): 35-39.

[29] Ma YH, Yan XY, Zhao HK et al. Effects of interleukin-1 receptor antagonist on collagen and matrix metalloproteinases in stress-shielded achilles tendons of rats. Orthopedics. 2012;35(8):e1238-1244.

[30] Miyatake S, Tohyama H, Kondo E, et al. Local administration of interleukin-1 receptor antagonist inhibits deterioration of mechanical properties of the stress-shielded patellar tendon. J Biomech. 200;41(4):884-889．