Archives of Orthopaedic and Trauma Surgery

, Volume 132, Issue 11, pp 1547–1553 | Cite as

Extracorporeal shock-wave therapy reduces progression of knee osteoarthritis in rabbits by reducing nitric oxide level and chondrocyte apoptosis

  • Zhe Zhao
  • Huiru Ji
  • Rufang Jing
  • Chunmei Liu
  • Mingbo Wang
  • Lei Zhai
  • Xiaodong Bai
  • Gengyan XingEmail author
Orthopaedic Surgery



The goal for treating osteoarthritis (OA) is finding ways to decrease joint pain and dysfunction and prevent and slow the cartilage degeneration. Extracorporeal shock-wave therapy (ESWT) has been found to improve motor dysfunction and ameliorate pain with OA in animals. However, few studies have found that it can prevent and slow joint degeneration in vivo. The aim of study was to investigate the effect of ESWT on OA in rabbit.

Materials and methods

A total of 30 male New Zealand white rabbits were divided into 3 groups: control, OA induced by anterior cruciate ligament transaction (ACLT), and ALCT plus ESWT. The animals were killed at 4 and 8 weeks. Nitric oxide (NO) level was measured in the synovial cavity of knee joints, and cartilage sections were graded macroscopically by a Mankin scoring system. Chondrocyte apoptosis was investigated by flow cytometry and the expression of active caspase 3 by indirect immunohistochemistry.


ESWT significantly reduced the NO level in the synovial cavity of knee joints (P < 0.05) and chondrocyte apoptosis (P < 0.05) of rabbits with OA. ESWT treatment significantly decreased the severity of cartilage lesions at both times as compared to rabbits with OA alone (P < 0.05).


ESWT reduced the progression of OA in rabbits. This effect may be related to decreased level of NO and is likely mediated by reduced chondrocyte apoptosis. ESWT may be a useful treatment for knee OA.


Extracorporeal shock wave Osteoarthritis Apoptosis Chondrocyte Nitric oxide 



Project was supported by National Natural Science Foundation of China (No 31172169).


  1. 1.
    Shirai T, Kobayashi M, Nishitani K, Satake T, Kuroki H, Nakagawa Y, Nakamura T (2011) Chondroprotective effect of alendronate in a rabbit model of osteoarthritis. J Orthop Res 29(10):1572–1577. doi: 10.1002/jor.21394 PubMedCrossRefGoogle Scholar
  2. 2.
    Hawker GA, Mian S, Bednis K, Stanaitis I (2011) Osteoarthritis year 2010 in review: non-pharmacologic therapy. Osteoarthr Cartil 19(4):366–374. doi: 10.1016/j.joca.2011.01.021 PubMedCrossRefGoogle Scholar
  3. 3.
    Kim HA, Blanco FJ (2007) Cell death and apoptosis in osteoarthritic cartilage. Curr Drug Targets 8(2):333–345PubMedCrossRefGoogle Scholar
  4. 4.
    van der Kraan PM, van den Berg WB (2012) Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthr Cartil 20(3):223–232. doi: 10.1016/j.joca.2011.12.003 PubMedCrossRefGoogle Scholar
  5. 5.
    Endres S, Weiskirch M, Hinz C, Hutter F, Wilke A (2008) Extracorporeal shock-wave therapy in the treatment of pseudoarthrosis: a case report. Cases J 1(1):276. doi: 10.1186/1757-1626-1-276 PubMedCrossRefGoogle Scholar
  6. 6.
    Albert JD, Meadeb J, Guggenbuhl P, Marin F, Benkalfate T, Thomazeau H, Chales G (2007) High-energy extracorporeal shock-wave therapy for calcifying tendinitis of the rotator cuff: a randomised trial. J Bone Joint Surg Br 89(3):335–341. doi: 10.1302/0301-620X.89B3.18249 PubMedCrossRefGoogle Scholar
  7. 7.
    Staples MP, Forbes A, Ptasznik R, Gordon J, Buchbinder R (2008) A randomized controlled trial of extracorporeal shock wave therapy for lateral epicondylitis (tennis elbow). J Rheumatol 35(10):2038–2046PubMedGoogle Scholar
  8. 8.
    Metzner G, Dohnalek C, Aigner E (2010) High-energy Extracorporeal Shock-Wave Therapy (ESWT) for the treatment of chronic plantar fasciitis. Foot Ankle Int 31(9):790–796. doi: 10.3113/FAI.2010.0790 PubMedCrossRefGoogle Scholar
  9. 9.
    Frisbie DD, Kawcak CE, McIlwraith CW (2009) Evaluation of the effect of extracorporeal shock wave treatment on experimentally induced osteoarthritis in middle carpal joints of horses. Am J Vet Res 70(4):449–454. doi: 10.2460/ajvr.70.4.449 PubMedCrossRefGoogle Scholar
  10. 10.
    Revenaugh MS (2005) Extracorporeal shock wave therapy for treatment of osteoarthritis in the horse: clinical applications. Vet Clin North Am Equine Pract 21(3):609–625. doi: 10.1016/j.cveq.2005.09.001
  11. 11.
    Ochiai N, Ohtori S, Sasho T, Nakagawa K, Takahashi K, Takahashi N, Murata R, Moriya H, Wada Y, Saisu T (2007) Extracorporeal shock wave therapy improves motor dysfunction and pain originating from knee osteoarthritis in rats. Osteoarthr Cartil 15(9):1093–1096. doi: 10.1016/j.joca.2007.03.011 PubMedCrossRefGoogle Scholar
  12. 12.
    Li X, Li J, Cheng K, Lin Q, Wang D, Zhang H, An H, Gao M, Chen A (2011) Effect of low-intensity pulsed ultrasound on MMP-13 and MAPKs signaling pathway in rabbit knee osteoarthritis. Cell Biochem Biophys 61(2):427–434. doi: 10.1007/s12013-011-9206-4 PubMedCrossRefGoogle Scholar
  13. 13.
    Wang FS, Yang KD, Kuo YR, Wang CJ, Sheen-Chen SM, Huang HC, Chen YJ (2003) Temporal and spatial expression of bone morphogenetic proteins in extracorporeal shock wave-promoted healing of segmental defect. Bone 32(4):387–396 pii: S8756328203000292PubMedCrossRefGoogle Scholar
  14. 14.
    Iwase Y, Kato J, Ohtaguro K (1989) Clinical experiences of Medstone 1050 ST on extracorporeal shock wave lithotripsy. Nihon Rinsho 47(12):2777–2780PubMedGoogle Scholar
  15. 15.
    Yoshioka M, Coutts RD, Amiel D, Hacker SA (1996) Characterization of a model of osteoarthritis in the rabbit knee. Osteoarthr Cartil 4(2):87–98 pii: S1063-4584(05)80318-8PubMedCrossRefGoogle Scholar
  16. 16.
    Vaterlein N, Lussenhop S, Hahn M, Delling G, Meiss AL (2000) The effect of extracorporeal shock waves on joint cartilage—an in vivo study in rabbits. Arch Orthop Trauma Surg 120(7–8):403–406PubMedCrossRefGoogle Scholar
  17. 17.
    Renz H, Rupp S (2009) Effects of shock waves on chondrocytes and their relevance in clinical practice. Arch Orthop Trauma Surg 129(5):641–647. doi: 10.1007/s00402-008-0668-9 PubMedCrossRefGoogle Scholar
  18. 18.
    Benson BM, Byron CR, Pondenis H, Stewart AA (2007) The effects of radial shock waves on the metabolism of equine cartilage explants in vitro. N Z Vet J 55(1):40–44. doi: 10.1080/00480169.2007.36733 PubMedCrossRefGoogle Scholar
  19. 19.
    Mayer-Wagner S, Ernst J, Maier M, Chiquet M, Joos H, Muller PE, Jansson V, Sievers B, Hausdorf J (2010) The effect of high-energy extracorporeal shock waves on hyaline cartilage of adult rats in vivo. J Orthop Res 28(8):1050–1056. doi: 10.1002/jor.21074 PubMedGoogle Scholar
  20. 20.
    Wang CJ, Weng LH, Ko JY, Wang JW, Chen JM, Sun YC, Yang YJ (2011) Extracorporeal shockwave shows regression of osteoarthritis of the knee in rats. J Surg Res 171(2):601–608. doi: 10.1016/j.jss.2010.06.042 PubMedCrossRefGoogle Scholar
  21. 21.
    Ciampa AR, de Prati AC, Amelio E, Cavalieri E, Persichini T, Colasanti M, Musci G, Marlinghaus E, Suzuki H, Mariotto S (2005) Nitric oxide mediates anti-inflammatory action of extracorporeal shock waves. FEBS Lett 579(30):6839–6845. doi: 10.1016/j.febslet.2005.11.023 PubMedCrossRefGoogle Scholar
  22. 22.
    Mariotto S, Cavalieri E, Amelio E, Ciampa AR, de Prati AC, Marlinghaus E, Russo S, Suzuki H (2005) Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production. Nitric Oxide 12(2):89–96. doi: 10.1016/j.niox.2004.12.005 PubMedCrossRefGoogle Scholar
  23. 23.
    Moretti B, Iannone F, Notarnicola A, Lapadula G, Moretti L, Patella V, Garofalo R (2008) Extracorporeal shock waves down-regulate the expression of interleukin-10 and tumor necrosis factor-alpha in osteoarthritic chondrocytes. BMC Musculoskelet Disord 9:16. doi: 10.1186/1471-2474-9-16 PubMedCrossRefGoogle Scholar
  24. 24.
    Abramson SB (2008) Nitric oxide in inflammation and pain associated with osteoarthritis. Arthr Res Ther 10(Suppl 2):S2. doi: 10.1186/ar2463 CrossRefGoogle Scholar
  25. 25.
    Hancock CM, Riegger-Krugh C (2008) Modulation of pain in osteoarthritis: the role of nitric oxide. Clin J Pain 24(4):353–365. doi: 10.1097/AJP.0b013e31815e5418 PubMedCrossRefGoogle Scholar
  26. 26.
    Li D, Wu Z, Duan Y, Hao D, Zhang X, Luo H, Chen B, Qiu G (2011) TNFalpha-mediated apoptosis in human osteoarthritic chondrocytes sensitized by PI3K-NF-kappaB inhibitor, not mTOR inhibitor. Rheumatol Int. doi: 10.1007/s00296-011-1929-4 Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Zhe Zhao
    • 1
  • Huiru Ji
    • 1
  • Rufang Jing
    • 2
  • Chunmei Liu
    • 1
  • Mingbo Wang
    • 3
  • Lei Zhai
    • 4
  • Xiaodong Bai
    • 1
  • Gengyan Xing
    • 1
    Email author
  1. 1.Department of Orthopaedic SurgeryThe General Hospital of Chinese People’s Army Police ForceBeijingPeople’s Republic of China
  2. 2.Ultrasonic Diagnosis DepartmentThe General Hospital of Chinese People’s Army Police ForceBeijingPeople’s Republic of China
  3. 3.Orthopaedic DepartmentArmed Police Inner Mongolia Unit HospitalHuhehaotePeople’s Republic of China
  4. 4.Orthopaedic DepartmentMedical College Affiliated Hospital of Chinese People’s Armed Police ForceTianjinPeople’s Republic of China

Personalised recommendations