Abstract
Purpose
Chronic tendinopathy is a degenerative process causing pain and disability. Current treatments include biophysical therapies, such as pulsed electromagnetic fields (PEMF). The aim of this study was to compare, for the first time, the functional in vitro response of human tendon cells to different dosages of PEMF, varying in field intensity and duration and number of exposures.
Methods
Tendon cells, isolated from human semitendinosus and gracilis tendons (hTCs; n = 6), were exposed to different PEMF treatments (1.5 or 3 mT for 8 or 12 h, single or repeated treatments). Scleraxis (SCX), COL1A1, COL3A1 and vascular endothelial growth factor-A (VEGF-A) expression and cytokine production were assessed.
Results
None of the different dosages provoked apoptotic events. Proliferation of hTCs was enhanced by all treatments, whereas only 3 mT-PEMF treatment increased cell viability. However, the single 1.5 mT-PEMF treatment elicited the highest up-regulation of SCX, VEGF-A and COL1A1 expression, and it significantly reduced COL3A1 expression with respect to untreated cells. The treated hTCs showed a significantly higher release of IL-1β, IL-6, IL-10 and TGF-β. Interestingly, the repeated 1.5 mT-PEMF significantly further increased IL-10 production.
Conclusions
1.5 mT-PEMF treatment was able to give the best results in in vitro healthy human tendon cell culture. Although the clinical relevance is not direct, this investigation should be considered an attempt to clarify the effect of different PEMF protocols on tendon cells, in particular focusing on the potential applicability of this cell source for regenerative medicine purpose, both in surgical and in conservative treatment for tendon disorders.
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Abbreviations
- PEMF:
-
Pulsed electromagnetic fields
- hTCs:
-
Human tendon cells
References
Assiotis A, Sachinis NP, Chalidis BE (2012) Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions: a prospective clinical study and review of the literature. J Orthop Surg Res 7:24
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
Brighton CT, Wang W, Seldes R, Zhang G, Pollack SR (2001) Signal transduction in electrically stimulated bone cells. J Bone Joint Surg Am 83-A:1514–1523
de Girolamo L, Stanco D, Galliera E, Vigano M, Colombini A, Setti S, Vianello E, Corsi Romanelli MM, Sansone V (2013) Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells. Cell Biochem Biophys 66:697–708
De Mattei M, Fini M, Setti S, Ongaro A, Gemmati D, Stabellini G, Pellati A, Caruso A (2007) Proteoglycan synthesis in bovine articular cartilage explants exposed to different low-frequency low-energy pulsed electromagnetic fields. Osteoarthr Cartil 15:163–168
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
de Mos M, van El B, DeGroot J, Jahr H, van Schie HT, van Arkel ER, Tol H, Heijboer R, van Osch GJ, Verhaar JA (2007) Achilles tendinosis: changes in biochemical composition and collagen turnover rate. Am J Sports Med 35:1549–1556
Denaro V, Ruzzini L, Barnaba SA, Longo UG, Campi S, Maffulli N, Sgambato A (2011) Effect of pulsed electromagnetic fields on human tenocyte cultures from supraspinatus and quadriceps tendons. Am J Phys Med Rehabil 90:119–127
Dingemanse R, Randsdorp M, Koes BW, Huisstede BM (2013) Evidence for the effectiveness of electrophysical modalities for treatment of medial and lateral epicondylitis: a systematic review. Br J Sports Med 48:957–965
Fassina L, Visai L, Benazzo F, Benedetti L, Calligaro A, De Angelis MG, Farina A, Maliardi V, Magenes G (2006) Effects of electromagnetic stimulation on calcified matrix production by SAOS-2 cells over a polyurethane porous scaffold. Tissue Eng 12:1985–1999
Galliera E, Corsi MM, Banfi G (2012) Platelet rich plasma therapy: inflammatory molecules involved in tissue healing. J Biol Regul Homeost Agents 26:35S–42S
Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R (2009) Low frequency pulsed electromagnetic field—a viable alternative therapy for arthritis. Indian J Exp Biol 47:939–948
Gomez-Ochoa I, Gomez-Ochoa P, Gomez-Casal F, Cativiela E, Larrad-Mur L (2011) Pulsed electromagnetic fields decrease proinflammatory cytokine secretion (IL-1beta and TNF-alpha) on human fibroblast-like cell culture. Rheumatol Int 31:1283–1289
Hosaka Y, Sakamoto Y, Kirisawa R, Watanabe T, Ueda H, Takehana K, Yamaguchi M (2004) Distribution of TNF receptors and TNF receptor-associated intracellular signaling factors on equine tendinocytes in vitro. Jpn J Vet Res 52:135–144
Ibrahim MS, Khan MA, Nizam I, Haddad FS (2013) Peri-operative interventions producing better functional outcomes and enhanced recovery following total hip and knee arthroplasty: an evidence-based review. BMC Med 11:37
Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G (2001) Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol 20:159–169
Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G (2007) Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol 207:267–274
Lui PP, Chan LS, Lee YW, Fu SC, Chan KM (2010) Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxf) 49:231–239
Maffulli N, Ewen SW, Waterston SW, Reaper J, Barrass V (2000) Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing. Am J Sports Med 28:499–505
Marcheggiani Muccioli GM, Grassi A, Setti S, Filardo G, Zambelli L, Bonanzinga T, Rimondi E, Busacca M, Zaffagnini S (2013) Conservative treatment of spontaneous osteonecrosis of the knee in the early stage: pulsed electromagnetic fields therapy. Eur J Radiol 82:530–537
Markov MS, Colbert AP (2000) Magnetic and electromagnetic field therapy. J Back Musculoskelet Rehabil 15:17–29
Moretti B, Notarnicola A, Moretti L, Setti S, De Terlizzi F, Pesce V, Patella V (2012) I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study. BMC Musculoskelet Disord 13:88
Ongaro A, Varani K, Masieri FF, Pellati A, Massari L, Cadossi R, Vincenzi F, Borea PA, Fini M, Caruso A, De Mattei M (2012) Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E(2) and cytokine release in human osteoarthritic synovial fibroblasts. J Cell Physiol 227:2461–2469
Pan Y, Dong Y, Hou W, Ji Z, Zhi K, Yin Z, Wen H, Chen Y (2013) Effects of PEMF on microcirculation and angiogenesis in a model of acute hindlimb ischemia in diabetic rats. Bioelectromagnetics 34:180–188
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
Rees JD, Stride M, Scott A (2013) Tendons—time to revisit inflammation. Br J Sports Med. doi:10.1136/bjsports-2012-091957
Ricchetti ET, Reddy SC, Ansorge HL, Zgonis MH, Van Kleunen JP, Liechty KW, Soslowsky LJ, Beredjiklian PK (2008) Effect of interleukin-10 overexpression on the properties of healing tendon in a murine patellar tendon model. J Hand Surg Am 33:1843–1852
Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL (1994) Tendon degeneration and chronic shoulder pain: changes in the collagen composition of the human rotator cuff tendons in rotator cuff tendinitis. Ann Rheum Dis 53:359–366
Rodriguez-De la Fuente AO, Alcocer-Gonzalez JM, Heredia-Rojas JA, Rodriguez-Padilla C, Rodriguez-Flores LE, Santoyo-Stephano MA, Castaneda-Garza E, Tamez-Guerra RS (2010) Effect of 60 Hz electromagnetic fields on the activity of hsp70 promoter: an in vivo study. Cell Biol Int Rep 19:e00014
Ross CL, Harrison BS (2013) Effect of pulsed electromagnetic field on inflammatory pathway markers in RAW 264.7 murine macrophages. J Inflamm Res 6:45–51
Rui YF, Lui PP, Li G, Fu SC, Lee YW, Chan KM (2010) Isolation and characterization of multipotent rat tendon-derived stem cells. Tissue Eng Part A 16:1549–1558
Schulze-Tanzil G, Al-Sadi O, Wiegand E, Ertel W, Busch C, Kohl B, Pufe T (2011) The role of pro-inflammatory and immunoregulatory cytokines in tendon healing and rupture: new insights. Scand J Med Sci Sports 21:337–351
Schulze-Tanzil G, Zreiqat H, Sabat R, Kohl B, Halder A, Muller RD, John T (2009) Interleukin-10 and articular cartilage: experimental therapeutical approaches in cartilage disorders. Curr Gene Ther 9:306–315
Shi HF, Xiong J, Chen YX, Wang JF, Qiu XS, Wang YH, Qiu Y (2013) Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study. BMC Musculoskelet Disord 14:35
Sollazzo V, Palmieri A, Pezzetti F, Massari L, Carinci F (2010) Effects of pulsed electromagnetic fields on human osteoblastlike cells (MG-63): a pilot study. Clin Orthop Relat Res 468:2260–2277
Strauch B, Patel MK, Rosen DJ, Mahadevia S, Brindzei N, Pilla AA (2006) Pulsed magnetic field therapy increases tensile strength in a rat Achilles’ tendon repair model. J Hand Surg Am 31:1131–1135
Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K, Sugawara K (2002) Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol Rev 8:6–48
Varani K, Gessi S, Merighi S, Iannotta V, Cattabriga E, Spisani S, Cadossi R, Borea PA (2002) Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils. Br J Pharmacol 136:57–66
Vianale G, Reale M, Amerio P, Stefanachi M, Di Luzio S, Muraro R (2008) Extremely low frequency electromagnetic field enhances human keratinocyte cell growth and decreases proinflammatory chemokine production. Br J Dermatol 158:1189–1196
Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, Cadossi R, Goldring MB, Borea PA, Varani K (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
Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83:835–870
Wojciak B, Crossan JF (1993) The accumulation of inflammatory cells in synovial sheath and epitenon during adhesion formation in healing rat flexor tendons. Clin Exp Immunol 93:108–114
Yost MG, Liburdy RP (1992) Time-varying and static magnetic fields act in combination to alter calcium signal transduction in the lymphocyte. FEBS Lett 296:117–122
Zorzi C, Dall’Oca C, Cadossi R, Setti S (2007) Effects of pulsed electromagnetic fields on patients’ recovery after arthroscopic surgery: prospective, randomized and double-blind study. Knee Surg Sports Traumatol Arthrosc 15:830–834
Acknowledgments
The Authors thank Dr. Alessandra Colombini for her precious help in RT-PCR analyses. The study has been partially supported by IGEA SpA, Clinical Biophysics, Carpi (Italy), and by the Italian Ministry of Health (Ricerca Corrente L1006).
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M. Viganò and E. Galliera have contributed equally to the manuscript.
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de Girolamo, L., Viganò, M., Galliera, E. et al. In vitro functional response of human tendon cells to different dosages of low-frequency pulsed electromagnetic field. Knee Surg Sports Traumatol Arthrosc 23, 3443–3453 (2015). https://doi.org/10.1007/s00167-014-3143-x
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DOI: https://doi.org/10.1007/s00167-014-3143-x