Advertisement

Electroacupuncture Delays Cartilage Degeneration by Modulating Nuclear Factor-κB Signaling Pathway

  • Guang-wen Wu
  • Jun Chen
  • Yun-mei Huang
  • Cai-bin Pan
  • Wen-lie Chen
  • Shi-mao Zhang
  • Wei Lin
  • Xian-xiang Liu
  • Ming-xia WuEmail author
Original Article

Abstract

Objective

To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA).

Methods

Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin’s score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis.

Results

EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01).

Conclusion

EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.

Keywords

osteoarthritis electroacupuncture synovial fluid cartilage cytokines nuclear factor-κB signaling pathway 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Goldring SR, Goldring MB. Clinical aspects, pathology and pathophysiology of osteoarthritis. J Musculoskelet Neuron Interact 2006;6:376–378.Google Scholar
  2. 2.
    Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 2010;1192:230–237.CrossRefGoogle Scholar
  3. 3.
    Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Infl amm 2014;2014:561459.Google Scholar
  4. 4.
    Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB. NFkappaB signaling: multiple angles to target OA. Curr Drug Targets 2010;11:599–613.CrossRefGoogle Scholar
  5. 5.
    Bowles RD, Mata BA, Bell RD, Mwangi TK, Huebner JL, Kraus VB, et al. In vivo luminescent imaging of NF-κB activity and serum cytokine levels predict pain sensitivities in a rodent model of osteoarthritis. Arthritis Rheum 2014;66:637–646.CrossRefGoogle Scholar
  6. 6.
    Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Int Med 2000;133:635–646.Google Scholar
  7. 7.
    Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991;325:87–91.CrossRefGoogle Scholar
  8. 8.
    Berenbaum F. New horizons and perspectives in the treatment of osteoarthritis. Arthritis Res Ther 2008;10 Suppl 2:S1.Google Scholar
  9. 9.
    Ahmed S, Anuntiyo J, Malemud CJ, Haqqi TM. Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: a review. Evid Based Complement Altern Med 2005;2:301–308.CrossRefGoogle Scholar
  10. 10.
    Fan AY, Miller DW, Bolash B, Bauer M, McDonald J, Faggert S, et al. Acupuncture’s role in solving the opioid epidemic: evidence, costeffectiveness, and care availability for acupuncture as a primary, non-pharmacologic method for pain relief and management—White Paper 2017. J Integr Med 2017;15:411–425.CrossRefGoogle Scholar
  11. 11.
    Chen N, Wang J, Mucelli A, Zhang X, Wang C. Electro-acupuncture is beneficial for knee osteoarthritis: the evidence from meta-analysis of randomized controlled trials. Am J Chin Med 2017;45:965–985.CrossRefGoogle Scholar
  12. 12.
    Wu MX, Li XH, Lin MN, Jia XR, Mu R, et al. Clinical study on the treatment of knee osteoarthritis of Shen-Sui insuffi ciency syndrome type by electroacupuncture. Chin J Integr Med 2010;16:291–297.CrossRefGoogle Scholar
  13. 13.
    Chen J, Liu XX. Tackling osteoarthritic knee pain with electroacupuncture. Chin J Integr Med 2018;24:803–805.CrossRefGoogle Scholar
  14. 14.
    Aoki E, Kasahara T, Hagiwara H, Sunaga M, Hisamitsu N, Hisamitsu T. Electroacupuncture and moxibustion influence the lipopolysaccharide-induced TNF-alpha production by macrophages. In Vivo 2005;19:495–500.Google Scholar
  15. 15.
    Wu G, Peng J, Wu M, Li Y, Huang Y, Lin R, et al. Experimental study of low-frequency electroacupuncture-induced differentiation of bone marrow mesenchymal stem cells into chondrocytes. Int J Mol Med 2011;27:79–86.Google Scholar
  16. 16.
    Huang Y, Wu G, Fan H, Ye J, Liu X. Electroacupuncture promotes chondrocyte proliferation via accelerated G1/S transition in the cell cycle. Int J Mol Med 2013;31:1443–1448.CrossRefGoogle Scholar
  17. 17.
    Guidance Suggestions for the Care and Use of Laboratory Animals. Beijing: Ministry of Science and Technology, National Development and Reform Commission, and Ministry of Finance, 2006. Accessed February 5, 2018 at http://www.most.gov.cn/fggw/zfwj/zfwj2006/200609/t20060930_54389.htm.Google Scholar
  18. 18.
    Liu XX, Li XH, Zhou JT. Experimental study on replicating knee osteoarthritis by modified’s modeling method. Chin J Integr Tradit West Med (Chin) 2005;25:1104–1108.Google Scholar
  19. 19.
    Chen S, Huang Y, Chen W, Wu G, Liao N, Li X, et al. Protective effects of the Tougu Xiaotong Capsule on morphology and osteoprotegerin/ nuclear factor-κB ligand expression in rabbits with knee osteoarthritis. Mol Med Rep 2016;13:419–425.CrossRefGoogle Scholar
  20. 20.
    Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteoarthritic human hips.. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 1971;53:523–537.Google Scholar
  21. 21.
    Kim J, Xu M, Xo R, Mates A, Wilson GL, Pearsall AW, et al. Mitochondrial DNA damage is involved in apoptosis caused by proinflammatory cytokines in human OA chondrocytes. Osteoarthritis Cartilage 2010;18:424–432.CrossRefGoogle Scholar
  22. 22.
    Aigner T, Söder S, Gebhard PM, McAlinden A, Haag J. Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis—structure, chaos and senescence. Nat Clin Pract Rheumatol 2007;3:391–399.CrossRefGoogle Scholar
  23. 23.
    Plaster R, Vieira WB, Alencar FA, Nakano EY, Liebano RE. Immediate effects of electroacupuncture and manual acupuncture on pain, mobility and muscle strength in patients with knee osteoarthritis. Acupunct Med 2014;32:236–241.CrossRefGoogle Scholar
  24. 24.
    Zwerina J, Redlich K, Polzer K, Joosten L, Krönke G, Distler J, et al. TNF-induced structural joint damage is mediated by IL-1. Proc Nat Acad Sci USA 2007;104:11742–11747.CrossRefGoogle Scholar
  25. 25.
    Kobayashi M, Squires GR, Mousa A, Tanzer M, Zukor DJ, Antoniou J, et al. Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum 2005;52:128–135.CrossRefGoogle Scholar
  26. 26.
    Raman S, FitzGerald U, Murphy JM. Interplay of inflammatory mediators with epigenetics and cartilage modifications in osteoarthritis. Front Bioeng Biotechnol 2018;6:22.CrossRefGoogle Scholar
  27. 27.
    Yu SM, Kim SJ. Protein phosphorylation on tyrosine restores expression and glycosylation of cyclooxygenase-2 by 2-deoxy-Dglucose-caused endoplasmic reticulum stress in rabbit articular chondrocyte. BMB Rep 2012;45:317–322.CrossRefGoogle Scholar
  28. 28.
    Botha-Scheepers S, Watt I, Slagboom E, de Crane AJ, Meulenbelt I, Rosendaal FR, et al. Innate production of tumour necrosis factor alpha and interleukin 10 is associated with radiological progression of knee osteoarthritis. Ann Rheum Dis 2008;67:1165–1169.CrossRefGoogle Scholar
  29. 29.
    Sakao K, Takahashi KA, Mazda O, Arai Y, Tonomura H, Inoue A, et al. Enhanced expression of interleukin-6, matrix metalloproteinase-13, and receptor activator of NF-κB ligand in cells derived from osteoarthritic subchondral bone. J Orthop Sci 2008;13:202–210.CrossRefGoogle Scholar
  30. 30.
    Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 2013;42:35–41.CrossRefGoogle Scholar
  31. 31.
    Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011;7:33–42.CrossRefGoogle Scholar
  32. 32.
    Yao Z, Xing L, Boyce BF. NF-kappaB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism. J Clin Invest 2009;119:3024–3034.CrossRefGoogle Scholar
  33. 33.
    Tong KM, Shieh DC, Chen CP, Tzeng CY, Wang SP, Huang KC, et al. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kB/p300 binding in human synovial fi broblasts. Cell Signal 2008;20:1478–1488.CrossRefGoogle Scholar
  34. 34.
    Mendis E, Kim MM, Rajapakse N, Kim SK. Suppression of cytokine production in lipopolysaccharide-stimulated mouse macrophages by novel cationic glucosamine derivative involves down-regulation of NF-κB and MAPK expressions. Bioorg Med Chem 2008;16:8390–8396.CrossRefGoogle Scholar
  35. 35.
    Olivotto E, Borzi RM, Vitellozzi R, Pagani S, Facchini A, Battistelli M, et al. Differential requirements for IKKα and IKKβ in the differentiation of primary human osteoarthritic chondrocytes. Arthritis Rheum 2008;58:227–239.CrossRefGoogle Scholar

Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine 2018

Authors and Affiliations

  • Guang-wen Wu
    • 1
  • Jun Chen
    • 1
  • Yun-mei Huang
    • 1
  • Cai-bin Pan
    • 1
  • Wen-lie Chen
    • 1
  • Shi-mao Zhang
    • 2
  • Wei Lin
    • 3
  • Xian-xiang Liu
    • 1
  • Ming-xia Wu
    • 4
    Email author
  1. 1.Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhouChina
  2. 2.Fujian Xiangxing Electronic Technology Co.Ltd.NingdeChina
  3. 3.Fujian Provincial Key Laboratory of Integrative Medicine on GeriatricsFuzhouChina
  4. 4.Department of AcupunctureSecond Affiliated People’s Hospital of Fujian University of Traditional Chinese MedicineFuzhouChina

Personalised recommendations