The Effects of Low-intensity Ultrasound on TGF-$\beta$1 Expression and Healing of Rat Femur Fracture

저강도 초음파가 흰쥐 대퇴골 골절치유와 TGF-$\beta$1의 발현에 미치는 영향

  • Nam, Ki-Won (Department of Physical Therapy, College of Health and welfare, Dongshin University)
  • 남기원 (동신대학교 보건복지대학 물리치료학과)
  • Received : 2009.10.26
  • Accepted : 2009.12.08
  • Published : 2009.12.25

Abstract

Purpose: The purpose of this study was to investigate the effects of low intensity pulsed ultrasound on TGF-$\beta$1 expression and healing of rat femur penetrating fractures. Methods: Rats were anesthetized with ketamine and xylazine. Using aseptic technique, we exposed the lateral right femoral diaphysis with removal of the periosteum. We made one hole along its long axis with an electrically-driven 1.8 mm diameter drill bit. Postoperatively, rats were divided into two groups (a control group, n=15; an experimental group, n=15). The experimental group was treated with low intensity pulsed ultrasound (pulse rate: 1:4, 0.5 W/$cm^2$, 10 minutes, 1 time per day) for 3 weeks. The control group was treated with sham ultrasound (with the US unit turned off). Results: The experimental group achieved more callus formation and TGF-$\beta$1 expression than the control group at the $7^{th}$, $14^{th}$ and $21^{st}$ days after low intensity pulsed ultrasound treatment. Conclusion: This study suggests that low intensity pulsed ultrasound facilitates bone fracture repair, possibly via increased TGF-$\beta$1 expression.

Keywords

References

  1. Kim J, Lee KM. The influence of leisure skill and leisure flow of leisure sports participants on leisure benefit. Korean Journal of Sociology of Sport. 2008;21(4):771-87.
  2. Kim BS. Depopulation and aging of rural areas in Korea-A case study of Goryeong-gun, Gyeongsangbuk-do. Journal of Korean Association of Regional Geographers. 2009;15(1): 36-52.
  3. Kang MJ, Han NH. Traffic accident analysis of Gwangju .Jeonnam province and traffic safety counterplan research. Journal of Korea Contents Association. 2007;7(1):184-89. https://doi.org/10.5392/JKCA.2007.7.1.184
  4. Lampasi M, Launay F, Jouve JL et al. Femoral lengthening over elastic stable intramedullary nailing in children using the monolateral external fixator. Musculoskelet Surg. 2009;93 (2):57-64. https://doi.org/10.1007/s12306-009-0032-4
  5. Hadjiargyron M, Mcleed K, Ryaby JP et al. Enhancement of fracture healing by low intensity ultrasound. Clin Orthop Relat Res. 1998;355:216-29.
  6. Ryeom TH, Kim SY, So YK et al. The risk factors of falls in the elderly. The Journal of the Korean Academy of Family Medicine. 2001;22(2):221-9.
  7. Chung HK, Kim JS, Park RJ. The effects of constant direct current on the new bone formation of fractured fibula in rabbits. J Kor Soc Phys Ther. 1994;6(1):95-107.
  8. Knight CA, Rutledge CR, Cox ME et al. Effect of superficial heat, deep heat, and active exercise warm-up on the extensibility of the plantar flexors. Phys Ther. 2001;81(6): 1206-14.
  9. Grazio S. Non-pharmacological treatment of musculoskeletal pain. Reumatizam. 2007;54(2):37-48.
  10. Hong CZ, Liu AA, Yu J. Ultrasound thermotherapu effect on the recovery of nerve conduction in experimental compression neuropathy. Arch Phy Med Rehabil. 1988;69 (6):410-4.
  11. Lai J, Pittelkow MR. Physiological effects of ultrasound mist on fibroblasts. Int J Dermatol. 2007;46(6):587-93. https://doi.org/10.1111/j.1365-4632.2007.02914.x
  12. Busse JW, Bhandari M, Kulkanmi AV et al. The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. CMAJ. 2002;166(4):437-41,
  13. Yang KH, Parvizi J, Wang SJ et al. Exposure to low-intensity ultrasound increases aggrecan gene expression in a rat femur fracture model. J Orthop Res. 1996;14(5):802-9. https://doi.org/10.1002/jor.1100140518
  14. Klug W, Franke WG, Knoch HG. Scintigraphic control of bone-fracture healing under ultrasonic stimulation: an animal experimental study. Eur J Nucl Med. 1986;11(12): 494-7.
  15. Rawool NM, Goldberg BB, Forsberg F et al. Power Doppler assessment of vascular changes during fracture treatment with low-intensity ultrasound. J Ultrasound Med. 2003;22(2): 145-53.
  16. Clases L, Willie B. The enhancement of bone regeneration by ultrasound. Prog Biophys Mol Biol. 2007;93(1-3):384-98. https://doi.org/10.1016/j.pbiomolbio.2006.07.021
  17. Lee HK. The effects of low-intensity ultrasound and laser on healing of bone fracture. Daegu University. Dissertation of Master's Degree. 2003.
  18. Noda M, Camilliere JJ. In vivo stimulation of bone formation by transforming growth factor-beta. Endocrinology. 1989; 124(6):2991-4. https://doi.org/10.1210/endo-124-6-2991
  19. Bolander ME. Regulation of fracture repair by growth factors. Proc Soc Exp Biol Med. 1992;200(2):165-70.
  20. Critchlow MA, Bland YS, Ashhurst DE. The effect of exogenous transforming growth factor-beta 2 on healing fractures in the rabbit. Bone. 1995;16(5):521-7. https://doi.org/10.1016/8756-3282(95)00085-R
  21. Matsumoto K, Matsunaga S, Imamura T et al. Expression and distribution of transforming growth factor-beta and decorin during fracture healing. In Vivo. 1994;8(2):215-9.
  22. Joyce ME, Roberts AB, Sporn MB et al. Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol. 1990;110(6):2195- 207. https://doi.org/10.1083/jcb.110.6.2195
  23. Chiba S, Okada K, Lee K et al. Molecular analysis of defect healing in rat diaphyseal bone. J Vet Med Sci. 2001;63(4):603- 8.
  24. ter Haar G. Therapeutic ultrasound. Euro J Ultrasound. 1999;9(1):3-9. https://doi.org/10.1016/S0929-8266(99)00013-0
  25. Sicard-Rosenbaum L, Danoff JV, Guthrie JA et al. Effects of energy-matched pulsed and continuous ultrasound on tumor growth in mice. Phys Ther. 1998;78(3):271-7.
  26. Chao EY, Inoue N. Biophysical stimulation of bone fracture repair, regeneration and remodelling. Eur Cell Mater. 2003;6: 72-84.
  27. Ardan NI Jr, Janes JM, Herrick JF. Ultrasonic energy and surgically produced defects in bone. J Bone Joint Surg Am. 1957;39-A(2):394-402.
  28. Della Rocca GJ. The science of ultrasound therapy for fracture healing. Indian J Orthop. 2009;43(2):121-6. https://doi.org/10.4103/0019-5413.50845
  29. Rubin C, Bolander M, Ryaby JP et al. The use of low-intensity ultrasound to accelerate the healing of fractures. J Bone Joint Surg Am. 2001;83-A(2):259-70.
  30. Dijkman BG, Sprague S, Bhandari M. Low-intensity pulsed ultrasound: Nonunions. Indian J Orthop. 2009;43(2);141-8. https://doi.org/10.4103/0019-5413.50848
  31. Della Rocca GJ. The science of ultrasound therapy for fracture healing. Indian J Otrhop. 2009;43(2):121-6. https://doi.org/10.4103/0019-5413.50845
  32. Heckman JD, Sarasohn-Kahn J. The economics of treating tibia fractures: the cost of delayed unions. Bull Hosp Joint Dis. 1996;56(1):63-72.
  33. Romano CL, Romano D, Loqoluso N. Low-intensity pulsed ultrasound for the treatment of bone delayed union or nonunion: a review. Ultrasound Med Biol. 2009;35(4):529-36. https://doi.org/10.1016/j.ultrasmedbio.2008.09.029
  34. Miyazono K. Positive and negative regulation of TFG-beta signaling. J Cell Sci. 2000;113(Pt7):1101-9.
  35. Wrana JL, Attisano L, Wieser R et al. Mechanism of activation of the TGF-beta receptor. Nature. 1994;370(6488):341-7. https://doi.org/10.1038/370341a0
  36. Tang Y, Wu X, Lei W et al. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. 2009;15(7):757-65. https://doi.org/10.1038/nm.1979
  37. Sakai K, Mohtai M, Iwamoto Y. Fluid shear stress increases transforming growth factor beta 1 expression in human osteoblast-like cells: modulation by cation channel blockades. Calcif Tissue Int. 1998;63(6):515-20. https://doi.org/10.1007/s002239900567
  38. Harle J, Mayia F, Olsen I et al. Effects of ultrasound on transforming growth factor-$\beta$ genes in bone cells. Eur Cell Mater. 2005;10:70-6.
  39. Ebisawa K, Hata K, Okada K et al. Ultrasound enhances transforming growth factor beta-mediated chondrocyte differentiation of human mesenchymal stem cells. Tissue Eng. 2004;10(5-6):921-9. https://doi.org/10.1089/1076327041348437
  40. Min SG, Chun JS, Yong JH et al. The effects of pulsed ultrasound on the bone healing processin fracture model of diabetes mellitus rat. J Kor Soc Phys Ther. 2006;18(2):47-58.
  41. Lee KH, Lee YI, Cho KC et al. Expression of TGF- $\beta$ I and II ligands and receptors at epiphysealplate and fracture callus. J Korean Orthop. 1998;33(2):458-65.