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Effect on bone healing by the application of low intensity pulsed ultrasound after injection of adipose tissue-derived stem cells at the implantation of titanium implant in the tibia of diabetes-induced rat

당뇨유도 백서 경골에 티타늄 임플란트 매식 시 지방조직 유래 줄기세포 주입 후 저출력 초음파 적용이 골치유에 미치는 영향

  • Jung, Tae-Young (Department of Oral and Maxillofacial Surgery, Inje University Pusan Paik Hospital) ;
  • Park, Sang-Jun (Department of Oral and Maxillofacial Surgery, Inje University Pusan Paik Hospital) ;
  • Hwang, Dae-Suk (Department of Oral and Maxillofacial Surgery, Pusan National University School of Dentistry) ;
  • Kim, Yong-Deok (Department of Oral and Maxillofacial Surgery, Pusan National University School of Dentistry) ;
  • Lee, Soo-Woon (Department of Oral and Maxillofacial Surgery, Inje University Haeundae Paik Hospital) ;
  • Kim, Uk-Kyu (Department of Oral and Maxillofacial Surgery, Pusan National University School of Dentistry)
  • 정태영 (인제대학교 부산백병원 구강악안면외과) ;
  • 박상준 (인제대학교 부산백병원 구강악안면외과) ;
  • 황대석 (부산대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 김용덕 (부산대학교 치의학전문대학원 구강악안면외과학교실) ;
  • 이수운 (인제대학교 해운대백병원 구강악안면외과) ;
  • 김욱규 (부산대학교 치의학전문대학원 구강악안면외과학교실)
  • Received : 2011.03.08
  • Accepted : 2011.07.25
  • Published : 2011.08.31

Abstract

Introduction: This study examined the effect of the application of low intensity pulsed ultrasound on bone healing after an injection of adipose tissue-derived stem cells (ADSCs) during the implantation of a titanium implant in the tibia of diabetes-induced rats. Materials and Methods: Twelve Sprague-Dawely rats were used. After inducing diabetes, the ADSCs were injected into the hole for the implant. Customized screw type implants, 2.0 mm in diameter and 3.5 mm in length, were implanted in both the tibia of the diabetes-induced rats. After implantation, LIPUS was applied with parameters of 3 MHz, 40 mW/$cm^2$, and 10 minutes for 7 days to the left tibiae (experimental group) of the diabetesinduced rats. The right tibiae in each rat were used in the control group. At 1, 2 and 4 week rats were sacrificed, and the bone tissues of both tibia were harvested. The bone tissues of the three rats in each week were used for bone-to-implant contact (BIC) and bone area (BA) analyses and the bone tissues of one rat were used to make sagittal serial sections. Results: In histomorphometric analyses, the BIC in the experimental and control group were respectively, $39.00{\pm}18.17%$ and $42.87{\pm}9.27%$ at 1 week, $43.74{\pm}6.83%$ and $32.27{\pm}6.00%$ at 2 weeks, and $32.62{\pm}11.02%$ and $47.10{\pm}9.77%$ at 4 weeks. The BA in experimental and control group were respectively, $37.28{\pm}3.68%$ and $31.90{\pm}2.84%$ at 1 week, $20.62{\pm}2.47%$ and $15.64{\pm}2.69%$ at 2 weeks, and $11.37{\pm}4.54%$ and $17.69{\pm}8.77%$ at 4 weeks. In immunohistochemistry analyses, Osteoprotegerin expression was strong at 1 and 2 weeks in the experimental group than the control group. Receptor activator of nuclear factor kB ligand expression showed similar staining at each week in the experimental and control group. Conclusion: These results suggest that the application of low intensity pulsed ultrasound after an injection of adipose tissue-derived stem cells during the implantation of titanium implants in the tibia of diabetes-induced rats provided some positive effect on bone regeneration at the early stage after implantation. On the other hand, this method is unable to increase the level of osseointegration and bone regeneration of the implant in an uncontrolled diabetic patient.

Keywords

References

  1. Misch CE. Contemporary implant dentistry. 3rd ed. Seoul: Daehan Narae Publishing; 2009.
  2. Min HK. Clinical characteristics of diabetes in Korea. J Korean Diabets Assoc 1992;16:163-74.
  3. Shin CS, Kim HK, Kim WB, Park KS, Kim SY, Cho BY, et al. Incidence of diabetes mellitus in Yonchon county, Korea. J Korean Diabets Assoc 1996;20:264-72.
  4. He H, Liu R, Desta T, Leone C, Gerstenfeld LC, Graves DT. Diabetes causes decreased osteoclastogenesis, reduced bone formation and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss. Endocrinology 2004;145:447-52. https://doi.org/10.1210/en.2003-1239
  5. Santana RB, Xu L, Chase HB, Amar S, Graves DT, Trackman PC. A role for advanced glycation end products in diminished bone healing in type 1 diabetes. Diabetes 2003;52:1502-10. https://doi.org/10.2337/diabetes.52.6.1502
  6. Weiss RE, Gorn AH, Nimni ME. Abnormalities in the biosynthesis of cartilage and bone proteoglycans in experimental diabetes. Diabetes 1981;30:670-7. https://doi.org/10.2337/diabetes.30.8.670
  7. Nevins ML, Karimbux NY, Weber HP, Giannobile WV, Fiorellini JP. Wound healing around endosseous implants in experimental diabetes. Int J Oral Maxillofac Implants 1998;13:620-9.
  8. McCracken M, Lemons JE, Rahemtulla F, Prince CW, Feldman D. Bone response to titanium alloy implants placed in diabetic rats. Int J Oral Maxillofac Implants 2000;15:345-54.
  9. Duarte LR. The stimulation of bone growth by ultrasound. Arch Orthop Trauma Surg 1983;101:153-9. https://doi.org/10.1007/BF00436764
  10. Yang KH, Parvizi J, Wang SJ, Lewallen DG, Kinnick RR, Greenleaf JF, et al. Exposure to low intensity ultrasound increases aggrecan gene expression in a rat femur fracture model. J Orthop Res 1996;14:802-9. https://doi.org/10.1002/jor.1100140518
  11. Eberson CP, Hogan KA, Moore DC, Ehrlich MG. Effect of lowintensity ultrasound stimulation on consolidation of the regenerate zone in a rat model of distraction osteogenesis. J Pediatr Orthop 2003;23:46-51.
  12. Yang RS, Lin WL, Chen YZ, Tang CH, Huang TH, Lu BY, et al. Regulation by ultrasound treatment on the integrin expression and differentiation of osteoblasts. Bone 2005;36:276-83. https://doi.org/10.1016/j.bone.2004.10.009
  13. Leung KS, Cheung WH, Zhang C, Lee KM, Lo HK. Low intensity pulsed ultrasound stimulates osteogenic activity of human periosteal cells. Clin Orthop Relat Res 2004;418:253-9. https://doi.org/10.1097/00003086-200401000-00044
  14. Chen YJ, Wang CJ, Yang KD, Chang PR, Huang HC, Huang YT, et al. Pertussis toxin-sensitive Galphai protein and ERK-dependent pathways mediate ultrasound promotion of osteogenic transcription in human osteoblasts. FEBS Lett 2003;554:154-8. https://doi.org/10.1016/S0014-5793(03)01157-8
  15. Tanzer M, Harvey E, Kay A, Morton P, Bobyn JD. Effect of noninvasive low intensity ultrasound on bone growth into porouscoated implants. J Orthop Res 1996;14:901-6. https://doi.org/10.1002/jor.1100140609
  16. Tanzer M, Kantor S, Bobyn JD. Enhancement of bone growth into porous intramedullary implants using non-invasive low intensity ultrasound. J Orthop Res 2001;19:195-9. https://doi.org/10.1016/S0736-0266(00)00034-6
  17. Dalla-Bona DA, Tanaka E, Inubushi T, Oka H, Ohta A, Okada H, et al. Cementoblast response to low- and high-intensity ultrasound. Arch Oral Biol 2008;53:318-23. https://doi.org/10.1016/j.archoralbio.2007.11.006
  18. Ikai H, Tamura T, Watanabe T, Itou M, Sugaya A, Iwabuchi S, et al. Low-intensity pulsed ultrasound accelerates periodontal wound healing after flap surgery. J Periodontal Res 2008;43:212-6. https://doi.org/10.1111/j.1600-0765.2007.01016.x
  19. Schortinghuis J, Bronckers AL, Stegenga B, Raghoebar GM, de Bont LG. Ultrasound to stimulate early bone formation in a distraction gap: a double blind randomised clinical pilot trial in the edentulous mandible. Arch Oral Biol 2005;50:411-20. https://doi.org/10.1016/j.archoralbio.2004.09.005
  20. Cowan CM, Shi YY, Aalami OO, Chou YF, Mari C, Thomas R, et al. Adipose derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol 2004;22:560-7. https://doi.org/10.1038/nbt958
  21. Dudas JR, Marra KG, Cooper GM, Penascino VM, Mooney MP, Jiang S, et al. The osteogenic potential of adipose-derived stem cells for the repair of rabbit calvarial defects. Ann Plast Surg 2006;56:543-8. https://doi.org/10.1097/01.sap.0000210629.17727.bd
  22. Yoon E, Dhar S, Chun DE, Gharibjanian NA, Evans GR. In vivo osteogenic potential of human adipose-derived stem cells/poly lactide-co-glycolic acid constructs for bone regeneration in a rat critical-sized calvarial defect model. Tissue Eng 2007;13:619-27. https://doi.org/10.1089/ten.2006.0102
  23. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7. https://doi.org/10.1126/science.284.5411.143
  24. Hwang DS, Kim UK, Chang MC, Kim YD, Shin SH, Chung IK. Osteogenic differentiation of stem cells in a gelatin-hydroxyapatite nanocomposite. Tissue Eng Regen Med 2009;6:1107-13.
  25. Kim MG, Jung IK, Shin SH, Kim CH, Kim BJ, Kim JH, et al. Effect of adipose-derived stem cells on bone healing on titanium implant in tibia of diabetes mellitus induced rats. J Korean Assoc Oral Maxillofac Surg 2010;36:392-401. https://doi.org/10.5125/jkaoms.2010.36.5.392
  26. Marvel S, Okrasinski S, Bernacki SH, Loboa E, Dayton PA. The development and validation of a LIPUS system with preliminary observations of ultrasonic effects on human adult stem cells. IEEE Trans Ultrason Ferroelectr Freg Control 2010;57:1977-84. https://doi.org/10.1109/TUFFC.2010.1645
  27. Hui CF, Chan CW, Qin L, Li G, Lee KM, Hu YY, et al. Osteogenic enhancement of low intensity pulsed ultrasound on bone marrow mesenchymal stem cell. Bone 2008;43:78.
  28. Angle SR, Sena K, Sumner DR, Virdi AS. Osteogenic differentiation of rat bone marrow stromal cells by various intensities of low-intensity pulsed ultrasound. Ultrasonics 2011;51:281-8. https://doi.org/10.1016/j.ultras.2010.09.004
  29. Jeong SY, Shin SH, Kim UK, Park BS, Chung IK. The study of bone mineral density in the mandible of streptozotocin-induced diabetic rats. J Korean Assoc Oral Maxillofac Surg 2002;28:95-102.
  30. Wu JR, Du GH. Temperature elevation generated by a focused Gaussian beam of ultrasound. Ultrasound Med Biol 1990;16:489-98. https://doi.org/10.1016/0301-5629(90)90171-8
  31. Chang WH, Sun JS, Chang SP, Lin JC. Study of thermal effects of ultrasound stimulation on fracture healing. Bioelectromagnetics 2002;23:256-63. https://doi.org/10.1002/bem.10009
  32. Dyson M. Non-thermal cellular effects of ultrasound. Br J Cancer Suppl 1982;45:165-71.
  33. Dinno MA, Dyson M, Young SR, Mortimer AJ, Hart J, Crum LA. The significance of membrane changes in the safe and effective use of therapeutic and diagnostic ultrasound. Phys Med Biol 1989;34:1543-52. https://doi.org/10.1088/0031-9155/34/11/003
  34. Rawool NM, Goldberg BB, Forsberg F, Winder AA, Hume E. Power Doppler assessment of vascular changes during fracture treatment with low-intensity ultrasound. J Ultrasound Med 2003;22:145-53. https://doi.org/10.7863/jum.2003.22.2.145
  35. Claes L, Willie B. The enhancement of bone regeneration by ultrasound. Prog Biophys Mol Biol 2007;93:384-98. https://doi.org/10.1016/j.pbiomolbio.2006.07.021
  36. Rubin C, Bolander M, Ryaby JP, Hadjiargyrou M. The use of low-intensity ultrasound to accelerate the healing of fractures. J Bone Joint Surg Am 2001;83-A:259-70. https://doi.org/10.1302/0301-620X.83B2.10763
  37. Sena K, Leven RM, Mazhar K, Sumner DR, Virdi AS. Early gene response to low-intensity pulsed ultrasound in rat osteoblastic cells. Ultrasound Med Biol 2005;31:703-8. https://doi.org/10.1016/j.ultrasmedbio.2005.01.013
  38. Hadjiargyrou M, McLeod K, Ryaby JP, Rubin C. Enhancement of fracture healing by low intensity ultrasound. Clin Orthop Relat Res 1998;(355 Suppl):S216-29.
  39. Tsai CL, Chang WH, Liu TK. Preliminary studies of duration and intensity of ultrasonic treatments on fracture repair. Chin J Physiol 1992;35:21-6.
  40. Tanzer M, Harvey E, Kay A, Morton P, Bobyn JD. Effect of noninvasive low intensity ultrasound on bone growth into porouscoated implants. J Orthop Res 1996;14:901-6. https://doi.org/10.1002/jor.1100140609
  41. Wang FS, Kuo YR, Wang CJ, Yang KD, Chang PR, Huang YT, et al. Nitric oxide mediates ultrasound-induced hypoxia-inducible factor-1alpha activation and vascular endothelial growth factor-A expression in human osteoblasts. Bone 2004;35:114-23. https://doi.org/10.1016/j.bone.2004.02.012
  42. Nolte PA, van der Krans A, Patka P, Janssen IM, Ryaby JP, Albers GH. Low-intensity pulsed ultrasound in the treatment of nonunions. J Trauma 2001;51:693-702. https://doi.org/10.1097/00005373-200110000-00012
  43. Korstjens CM, Nolte PA, Burger EH, Albers GH, Semeins CM, Aartman IH, et al. Stimulation of bone cell differentiation by low-intensity ultrasound-a histomorphometric in vitro study. J Orthop Res 2004;22:495-500. https://doi.org/10.1016/j.orthres.2003.09.011
  44. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002;13:4279-95. https://doi.org/10.1091/mbc.E02-02-0105
  45. Lin Y, Liu L, Li Z, Qiao J, Wu L, Tang W, et al. Pluripotency potential of human adipose-derived stem cells marked with exogenous green fluorescent protein. Mol Cell Biochem 2006;291:1-10. https://doi.org/10.1007/s11010-006-9188-5
  46. Hofmann S, Hagenmuller H, Koch AM, Muller R, Vunjak-Novakovic G, Kaplan DL, et al. Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds. Biomaterials 2007;28:1152-62. https://doi.org/10.1016/j.biomaterials.2006.10.019
  47. Li X, Yao J, Wu L, Jing W, Tang W, Lin Y, et al. Osteogenic induction of adipose-derived stromal cells: not a requirement for bone formation in vivo. Artif Organs 2010;34:46-54. https://doi.org/10.1111/j.1525-1594.2009.00795.x
  48. Jeon O, Rhie JW, Kwon IK, Kim JH, Kim BS, Lee SH. In vivo bone formation following transplantation of human adipose-derived stromal cells that are not differentiated osteogenically. Tissue Eng Part A 2008;14:1285-94. https://doi.org/10.1089/ten.tea.2007.0253
  49. Kruyt MC, Dhert WJ, Oner FC, van Blitterswijk CA, Verbout AJ, de Bruijn JD. Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered constructs in goats. Biomaterials 2007;28:1798-805. https://doi.org/10.1016/j.biomaterials.2006.11.038
  50. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473:139-46. https://doi.org/10.1016/j.abb.2008.03.018
  51. Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F, Rey JM, Garcia-Garcia A. RANK/RANKL/OPG role in distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:679-86. https://doi.org/10.1016/j.tripleo.2009.10.042
  52. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology 2001;142:5050-55. https://doi.org/10.1210/en.142.12.5050
  53. Boyce BF, Xing L. The RANKL/RANK/OPG pathway. Curr Osteoporos Rep 2007;5:98-104. https://doi.org/10.1007/s11914-007-0024-y
  54. Borsje MA, Ren Y, de Haan-Visser HW, Kuijer R. Comparison of low-intensity pulsed ultrasound and pulsed electromagnetic field treatments on OPG and RANKL expression in human osteoblast-like cells. Angle Orthod 2010;80:498-503. https://doi.org/10.2319/060809-318.1

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