Skip to main content


Log in

Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

  • Original Paper
  • Published:
International Orthopaedics Aims and scope Submit manuscript



Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage.


Explants of porcine cartilage and human osteoarthritic cartilage were cultured for four weeks and subjected to daily LIPUS or PEMF treatments. At one, two, three and four weeks follow-up explants were prepared for histological assessment or gene expression (porcine only).


Non-treated porcine explants showed signs of atrophy of the superficial zone starting at one week. Treated explants did not. In LIPUS-treated explants cell clusters were observed. In PEMF-treated explants more hypertrophic-like changes were observed at later follow up. Newly synthesized tissue was present in treated explants. Gene expression profiles did indicate differences between the two methods. Both methods reduced expression of the aggrecan and collagen type II gene compared to the control. LIPUS treatment of human cartilage samples resulted in a reduction of degeneration according to Mankin scoring. PEMF treatment did not.


LIPUS or PEMF prevented degenerative changes in pig knee cartilage explants. LIPUS reduced degeneration in human cartilage samples. LIPUS treatment seems to have more potency in the treatment of osteoarthritis than PEMF treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others


  1. Lafeber FP, Intema F, van Roermund PM, Marijnissen AC (2006) Unloading joints to treat osteoarthritis, including joint distraction. Curr Opin Rheumatol 18:519–525

    Article  PubMed  Google Scholar 

  2. Mastbergen SC, Saris DB, Lafeber FP (2013) Functional articular cartilage repair: here, near, or is the best approach not yet clear? Nat Rev Rheumatol 9:277–290

    Article  CAS  PubMed  Google Scholar 

  3. Ploegmakers JJW, van Roermund PM, van Melkebeek J, Lammens J, Bijlsma JWJ, Lafeber FPJG, Marijnissen ACA (2005) Prolonged clinical benefit from joint distraction in the treatment of ankle osteoarthritis. Osteoarthr Cartil 13:582–588

    Article  CAS  PubMed  Google Scholar 

  4. Ivkovic A, Marijanovic I, Hudetz D, Porter RM, Pecina M, Evans CH (2011) Regenerative medicine and tissue engineering in orthopaedic surgery. Front Biosci (Elite Ed) 3:923–944

  5. Haapala J, Arokoski JP, Ronkko S, Agren U, Kosma VM, Lohmander LS, Tammi M, Helminen HJ, Kiviranta I (2001) Decline after immobilisation and recovery after remobilisation of synovial fluid IL1, TIMP, and chondroitin sulphate levels in young beagle dogs. Ann Rheum Dis 60:55–60

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Haapala J, Arokoski JPA, Hyttinen MM, Lammi M, Tammi M, Kovanen V, Helminen HJ, Kiviranta I (1999) Remobilization does not fully restore immobilization induced articular cartilage atrophy. Clin Orthop Rel Res 362:218–255

  7. Cook SD, Salkeld SL, Popich-Patron LS, Ryaby JP, Jones DG, Barrack RL (2001) Improved cartilage repair after treatment with low-intensity pulsed ultrasound. Clin Orthop Rel Res 391S:231–243

    Article  Google Scholar 

  8. Korstjens CM, van der Rijt RH, Albers GH, Semeins CM, Klein-Nulend J (2008) Low-intensity pulsed ultrasound affects human articular chondrocytes in vitro. Med Biol Eng Comput 46:1263–1270

    Article  CAS  PubMed  Google Scholar 

  9. Min BH, Woo JI, Cho HS, Choi BH, Park SJ, Choi MJ, Park SR (2006) Effects of low-intensity ultrasound (LIUS) stimulation on human cartilage explants. Scand J Rheumatol 35:305–311

    Article  PubMed  Google Scholar 

  10. Zhang ZJ, Huckle J, Francomano CA, Spencer RGS (2002) The influence of pulsed low-intensity ultrasound on matrix production of chondrocytes at different stages of differentiation: An explant study. Ultrasound Med Biol 28:1547–1553

    Article  PubMed  Google Scholar 

  11. Zhang ZJ, Huckle J, Francomano CA, Spencer RGS (2003) The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production. Ultrasound Med Biol 29:1645–1651

    Article  PubMed  Google Scholar 

  12. Aaron RK, Ciombor DM (1998) Therapeutic potential of electric fields in skeletal morphogenesis. In: Buckwalter JA, Ehrlich MG, Sandell LJ and Trippel SB (ed) Therapeutic potential of electric fields in skeletal morphogenesis. American Academy of Orthopaedic Surgeons, Rosemont, IL, pp 589–610

  13. Benazzo F, Cadossi M, Cavani F, Fini M, Giavaresi G, Setti S, Cadossi R, Giardino R (2008) Cartilage repair with osteochondral autografts in sheep: effect of biophysical stimulation with pulsed electromagnetic fields. J Orthop Res 26:631–642

    Article  PubMed  Google Scholar 

  14. Boopalan PR, Arumugam S, Livingston A, Mohanty M, Chittaranjan S (2011) Pulsed electromagnetic field therapy results in healing of full thickness articular cartilage defect. Int Orthop 35:143–148

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. De Mattei M, Pasello M, Pellati A, Stabellini G, Massari L, Gemmati D, Caruso A (2003) Effects of electromagnetic fields on proteoglycan metabolism of bovine articular cartilage explants. Connect Tissue Res 44:154–159

    Article  PubMed  Google Scholar 

  16. Fini M, Giavaresi G, Carpi A, Nicolini A, Setti S, Giardino R (2005) Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies. Biomed Pharmacother 59:388–394

    Article  CAS  PubMed  Google Scholar 

  17. Ongaro A, Pellati A, Masieri FF et al (2011) Chondroprotective effects of pulsed electromagnetic fields on human cartilage explants. Bioelectromagnetics 32:543–551

    Article  CAS  PubMed  Google Scholar 

  18. Vincenzi F, Targa M, Corciulo C et al (2013) Pulsed electromagnetic fields increased the anti-inflammatory effect of A(2)A and A(3) adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS ONE 8:e65561

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. De Mattei M, Caruso A, Pezzetti F, Pellati A, Stabellini G, Sollazzo V, Traina GC (2001) Effects of pulsed electromagnetic fields on human articular chondrocyte proliferation. Connect Tissue Res 42:269–279

    Article  PubMed  Google Scholar 

  20. De Mattei M, Pellati A, Pasello M, Ongaro A, Setti S, Massari L, Gemmati D, Caruso A (2004) Effects of physical stimulation with electromagnetic field and insulin growth factor-I treatment on proteoglycan synthesis of bovine articular cartilage. Osteoarthr Cartil OARS Osteoarthr Res Soc 12:793–800

    Article  Google Scholar 

  21. Fioravanti A, Nerucci F, Collodel G, Markoll R, Marcolongo R (2002) Biochemical and morphological study of human articular chondrocytes cultivated in the presence of pulsed signal therapy. Ann Rheum Dis 61:1032–1033

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Pezzetti F, De Mattei M, Caruso A, Cadossi R, Zucchini P, Carinci F, Traina GC, Sollazzo V (1999) Effects of pulsed electromagnetic fields on human chondrocytes: an in vitro study. Calcif Tissue Int 65:396–401

    Article  CAS  PubMed  Google Scholar 

  23. Sakai A, Suzuki K, Nakamura T, Norimura T, Tsuchiya T (1991) Effect of pulsing electromagnetic fields on cultured cartilage cells. Int Orthop 15:341–346

    Article  CAS  PubMed  Google Scholar 

  24. Schortinghuis J, Ruben JL, Raghoebar GM, Stegenga B (2004) Ultrasound to stimulate mandibular bone defect healing: a placebo-controlled single-blind study in rats. J Oral Maxillofac Surg 62:194–201

    Article  PubMed  Google Scholar 

  25. Choi BH, Woo JI, Min BH, Park SR (2006) Low-intensity ultrasound stimulates the viability and matrix gene expression of human articular chondrocytes in alginate bead culture. J Biomed Mater Res A 79:858–864

    Article  PubMed  Google Scholar 

  26. Bulstra SK, Drukker J, Kuijer R, Buurman WA, van der Linden AJ (1993) Thionin staining of paraffin and plastic embedded sections of cartilage. Biotech Histochem 68:20–28

    Article  CAS  PubMed  Google Scholar 

  27. Upton ML, Chen J, Guilak F, Setton LA (2003) Differential effects of static and dynamic compression on meniscal cell gene expression. J Orthop Res 21:963–969

  28. Zou L, Zou X, Chen L, Li H, Mygind T, Kassem M, Bunger C (2008) Multilineage differentiation of porcine bone marrow stromal cells associated with specific gene expression pattern. J Orthop Res 26:56–64

    Article  CAS  PubMed  Google Scholar 

  29. Jung M, Gotterbarm T, Gruettgen A, Vilei SB, Breusch S, Richter W (2005) Molecular characterization of spontaneous and growth-factor-augmented chondrogenesis in periosteum-bone tissue transferred into a joint. Histochem Cell Biol 123:447–456

  30. Chou CH, Cheng WT, Kuo TF, Sun JS, Lin FH, Tsai JC (2007) Fibrin glue mixed with gelatin/hyaluronic acid/chondroitin-6-sulfate tri-copolymer for articular cartilage tissue engineering: the results of real-time polymerase chain reaction. J Biomed Mater Res A 82:757–767

    Article  PubMed  Google Scholar 

  31. Lu L, Zhang Q, Pu LJ et al (2008) Dysregulation of matrix metalloproteinases and their tissue inhibitors is related to abnormality of left ventricular geometry and function in streptozotocin-induced diabetic minipigs. Int J Exp 89:125–137

    Article  CAS  Google Scholar 

  32. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  33. Aigner T, Stöss H, Weseloh G, Zeiler G, von der Mark K (1992) Activation of collagen type-II expression in osteoarthritic and rheumatoid cartilage. Virchows Arch B Cell Pathol Incl Mol Pathol 62:337-345

  34. Lotz MK, Otsuki S, Grogan SP, Sah R, Terkeltaub R, D’Lima D (2010) Cartilage cell clusters. Arthritis Rheum 62:2206–2218

    Article  PubMed Central  PubMed  Google Scholar 

  35. Gobbi A, Lad D, Petrera M, Karnatzikos G (2014) Symptomatic early osteoarthritis of the knee treated with pulsed electromagnetic fields: two-year follow-up. Cartilage 5:78-85

  36. McKibbin B, Maroudas A (1979) Nutrition and metabolism. In: Freeman MAR (ed) Nutrition and metabolism, 2nd edn. Pitman Medical, London, pp 461–486

    Google Scholar 

  37. O’Hara BP, Urban JPG, Maroudas A (1990) Influence of cyclic loading on the nutrition of articular cartilage. Ann Rheum Dis 49:536–539

    Article  PubMed Central  PubMed  Google Scholar 

  38. Pollack GH (2013) The Fourth Phase of Water. Beyond Solid, Liquid and Vapor. Ebner & Sons Publishers, Seattle, USA166

    Google Scholar 

  39. Zhao Q, Ovchinnikova K, Chai B, Yoo H, Magula J, Pollack GH (2009) Role of proton gradients in the mechanism of osmosis. J Phys Chem B 113:10708–10714

    Article  CAS  PubMed  Google Scholar 

  40. Zheng JM, Chin WC, Khijniak E, Khijniak E Jr, Pollack GH (2006) Surfaces and interfacial water: evidence that hydrophilic surfaces have long-range impact. Adv Colloid Interf Sci 127:19–27

    Article  CAS  Google Scholar 

  41. Paukkonen K, Jurvelin J, Helminen HJ (1986) Effects of immobilization on the articular cartilage in young rabbits. A quantitative light microscopic stereological study. Clin Orthop Relat Res 206:270–280

Download references


Mathias Berg Johansen and Madelica Pituca are gratefully acknowledged for their experimental work. The Physiostim® apparatus was kindly provided by Evert Jan van de Kamp from Pro-Motion Medical bv Zwijndrecht, The Netherlands.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Roel Kuijer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, L., Ren, Y., van Kooten, T.G. et al. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants. International Orthopaedics (SICOT) 39, 549–557 (2015).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: