A review of mechanisms by which low-intensity pulsed ultrasound affects bone regeneration

doi:10.7518/hxkq.2020.05.017

Abstract

Abstract:

Low-intensity pulsed ultrasound (LIPUS) is a common physical therapy to accelerate the healing of bone fracture and treat delayed union of bone fracture. Vessels, nerves, and bone tissue are essential constituents of bone system. Recently, increasing evidence has been revealed that LIPUS can not only promote bone regeneration by directly regulating osteoblasts, osteoblasts, mesenchymal stem cells, but also have a positive impact on the repair of bone healing through vessels and nerves. Thus, we reviewed and summarized the latest published literature about the molecular mechanism for the effects of LIPUS on bone regeneration, which might offer a promising therapy for bone-related diseases.

Key words: low-intensity pulsed ultrasound, bone regeneration, angiogenesis, nerve regeneration

CLC Number:

Jiang Yixuan, Gong Ping, Zhang Liang. A review of mechanisms by which low-intensity pulsed ultrasound affects bone regeneration[J]. West China Journal of Stomatology, 2020, 38(5): 571-575.

References 44

[1]	Yang MH, Lim KT, Choung PH , et al. Application of ultrasound stimulation in bone tissue engineering[J]. Int J Stem Cells, 2010,3(2):74-79. doi: 10.15283/ijsc.2010.3.2.74 URL pmid: 24855544
[2]	Harrison A, Lin S, Pounder N , et al. Mode & mechanism of low intensity pulsed ultrasound (LIPUS) in fracture repair[J]. Ultrasonics, 2016,70:45-52. doi: 10.1016/j.ultras.2016.03.016 URL pmid: 27130989
[3]	Bashardoust Tajali S, Houghton P, MacDermid JC, et al. Effects of low-intensity pulsed ultrasound therapy on fracture healing: a systematic review and meta-analysis[J]. Am J Phys Med Rehabil, 2012,91(4):349-367. doi: 10.1097/PHM.0b013e31822419ba URL pmid: 21904188
[4]	Wu SY, Xu XM, Sun JC , et al. Low-intensity pulsed ultrasound accelerates traumatic vertebral fracture healing by coupling proliferation of type H microvessels[J]. J Ultrasound Med, 2018,37(7):1733-1742. doi: 10.1002/jum.14525 URL pmid: 29363151
[5]	Zhu HX, Cai XZ, Lin T , et al. Low-intensity pulsed ultrasound enhances bone repair in a rabbit model of steroid-associated osteonecrosis[J]. Clin Orthop Relat Res, 2015,473(5):1830-1839. doi: 10.1007/s11999-015-4154-8 URL pmid: 25736917
[6]	Jung YJ, Kim R, Ham HJ , et al. Focused low-intensity pulsed ultrasound enhances bone regeneration in rat calvarial bone defect through enhancement of cell proliferation[J]. Ultrasound Med Biol, 2015,41(4):999-1007. doi: 10.1016/j.ultrasmedbio.2014.11.008 URL pmid: 25701528
[7]	Rubin C, Bolander M, Ryaby JP , et al. The use of low-intensity ultrasound to accelerate the healing of fractures[J]. J Bone Joint Surg Am, 2001,83(2):259-270. doi: 10.2106/00004623-200102000-00015 URL pmid: 11216689
[8]	Feng LF, Liu XH, Cao HJ , et al. A comparison of 1-and 3.2-MHz low-intensity pulsed ultrasound on osteogenesis on porous titanium alloy scaffolds: an in vitro and in vivo study[J]. J Ultrasound Med, 2019,38(1):191-202. doi: 10.1002/jum.14683 URL pmid: 29781183
[9]	Mishima H, Sugaya H, Yoshioka T , et al. The safety and efficacy of combined autologous concentrated bone marrow grafting and low-intensity pulsed ultrasound in the treatment of osteonecrosis of the femoral head[J]. Eur J Orthop Surg Traumatol, 2016,26(3):293-298. doi: 10.1007/s00590-016-1752-4 URL pmid: 26920362
[10]	Zu HY, Yi XT, Zhao DW . Transcriptome sequencing analysis reveals the effect of combinative treatment with low-intensity pulsed ultrasound and magnesium ions on hFOB1. 19 human osteoblast cells[J]. Mol Med Rep, 2018,18(1):749-762. doi: 10.3892/mmr.2018.9006 URL pmid: 29767241
[11]	Wang YJ, Qiu Y, Li J , et al. Low-intensity pulsed ultrasound promotes alveolar bone regeneration in a periodontal injury model[J]. Ultrasonics, 2018,90:166-172. doi: 10.1016/j.ultras.2018.06.015 URL pmid: 30049446
[12]	Zhou XY, Xu XM, Wu SY , et al. Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway[J]. Bone, 2018,110:47-57. doi: 10.1016/j.bone.2018.01.025 URL pmid: 29414599
[13]	Matsumoto K, Shimo T, Kurio N , et al. Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling[J]. J Cell Biochem, 2018,119(6):4352-4360. doi: 10.1002/jcb.26418 URL pmid: 28981158
[14]	Miyasaka M, Nakata H, Hao J , et al. Low-intensity pulsed ultrasound stimulation enhances heat-shock protein 90 and mineralized nodule formation in mouse Calvaria-derived osteoblasts[J]. Tissue Eng Part A, 2015,21(23/24):2829-2839. doi: 10.1089/ten.tea.2015.0234 URL
[15]	Bandow K, Nishikawa Y, Ohnishi T , et al. Low-intensity pulsed ultrasound (LIPUS) induces RANKL, MCP-1, and MIP-1beta expression in osteoblasts through the angiotensin Ⅱ type 1 receptor[J]. J Cell Physiol, 2007,211(2):392-398. doi: 10.1002/jcp.20944 URL pmid: 17167786
[16]	Manaka S, Tanabe N, Kariya T , et al. Low-intensity pulsed ultrasound-induced ATP increases bone formation via the P2X7 receptor in osteoblast-like MC3T3-E1 cells[J]. FEBS Lett, 2015,589(3):310-318. doi: 10.1016/j.febslet.2014.12.013 URL pmid: 25542352
[17]	Kaur H, Siraki AG, Uludağ H , et al. Role of reactive oxygen species during low-intensity pulsed ultrasound application in MC-3T3 E1 pre-osteoblast cell culture[J]. Ultrasound Med Biol, 2017,43(11):2699-2712. doi: 10.1016/j.ultrasmedbio.2017.07.002 URL pmid: 28807447
[18]	Tassinary JAF, Lunardelli A, Basso BS , et al. Low-intensity pulsed ultrasound (LIPUS) stimulates mineralization of MC3T3-E1 cells through calcium and phosphate uptake[J]. Ultrasonics, 2018,84:290-295. doi: 10.1016/j.ultras.2017.11.011 URL pmid: 29182945
[19]	Tabuchi Y, Sugahara Y, Ikegame M , et al. Genes responsive to low-intensity pulsed ultrasound in MC3T3-E1 preosteoblast cells[J]. Int J Mol Sci, 2013,14(11):22721-22740. doi: 10.3390/ijms141122721 URL pmid: 24252911
[20]	Suzuki N, Hanmoto T, Ikegame M , et al. 9. effects of low-intensity pulsed ultrasound (LIPUS) on osteoclasts and osteoblasts: analysis using an assay system with fish scale as a model of bone[J]. J Orthop Trauma, 2016,30(8):S4. doi: 10.1097/01.bot.0000489981.32706.91 URL pmid: 27441769
[21]	Hanmoto T, Tabuchi Y, Ikegame M , et al. Effects of low-intensity pulsed ultrasound on osteoclasts: analysis with goldfish scales as a model of bone[J]. Biomed Res, 2017,38(1):71-77. doi: 10.2220/biomedres.38.71 URL pmid: 28239034
[22]	Meng JH, Hong JQ, Zhao CC , et al. Low-intensity pulsed ultrasound inhibits RANKL-induced osteoclast formation via modulating ERK-c-Fos-NFATc1 signaling cascades[J]. Am J Transl Res, 2018,10(9):2901-2910. URL pmid: 30323876
[23]	Verma S, Rajaratnam JH, Denton J , et al. Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis[J]. J Clin Pathol, 2002,55(9):693-698. doi: 10.1136/jcp.55.9.693 URL pmid: 12195001
[24]	Kusuyama J, Bandow K, Shamoto M , et al. Low intensity pulsed ultrasound (LIPUS) influences the multilineage differentiation of mesenchymal stem and progenitor cell lines through ROCK-Cot/Tpl2-MEK-ERK signaling pathway[J]. J Biol Chem, 2014,289(15):10330-10344. doi: 10.1074/jbc.M113.546382 URL pmid: 24550383
[25]	Costa V, Carina V, Fontana S , et al. Osteogenic commitment and differentiation of human mesenchymal stem cells by low-intensity pulsed ultrasound stimulation[J]. J Cell Physiol, 2018,233(2):1558-1573. doi: 10.1002/jcp.26058 URL pmid: 28621452
[26]	He RX, Zhou WC, Zhang Y , et al. Combination of low-intensity pulsed ultrasound and C3H10T1/2 cells promotes bone-defect healing[J]. Int Orthop, 2015,39(11):2181-2189. doi: 10.1007/s00264-015-2898-0 URL pmid: 26169839
[27]	Sena K, Angle SR, Kanaji A , et al. Low-intensity pulsed ultrasound (LIPUS) and cell-to-cell communication in bone marrow stromal cells[J]. Ultrasonics, 2011,51(5):639-644. doi: 10.1016/j.ultras.2011.01.007 URL
[28]	Xiao WX, Xu Q, Zhu ZM , et al. Different performances of CXCR4, integrin-1β and CCR-2 in bone marrow stromal cells (BMSCs) migration by low-intensity pulsed ultrasound stimulation[J]. Biomedizinische Tech, 2017,62(1):89-95.
[29]	Maes C, Goossens S, Bartunkova S , et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones[J]. EMBO J, 2010,29(2):424-441. doi: 10.1038/emboj.2009.361 URL pmid: 20010698
[30]	Maes C, Kobayashi T, Selig MK , et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels[J]. Dev Cell, 2010,19(2):329-344. doi: 10.1016/j.devcel.2010.07.010 URL pmid: 20708594
[31]	Katano M, Naruse K, Uchida K , et al. Low intensity pulsed ultrasound accelerates delayed healing process by reducing the time required for the completion of endochondral ossification in the aged mouse femur fracture model[J]. Exp Anim, 2011,60(4):385-395. doi: 10.1538/expanim.60.385 URL pmid: 21791878
[32]	Cheung WH, Chow SK, Sun MH , et al. Low-intensity pulsed ultrasound accelerated callus formation, angiogenesis and callus remodeling in osteoporotic fracture healing[J]. Ultrasound Med Biol, 2011,37(2):231-238. doi: 10.1016/j.ultrasmedbio.2010.11.016 URL
[33]	Martinez de Albornoz P, Khanna A, Longo UG , et al. The evidence of low-intensity pulsed ultrasound for in vitro, animal and human fracture healing[J]. Br Med Bull, 2011,100:39-57. doi: 10.1093/bmb/ldr006 URL pmid: 21429948
[34]	Korstjens CM, Rutten S, Nolte PA , et al. Low-intensity pulsed ultrasound increases blood vessel size during fracture healing in patients with a delayed-union of the osteotomized fibula[J]. Histol Histopathol, 2018,33(7):737-746. doi: 10.14670/HH-11-972 URL pmid: 29436706
[35]	Hanawa K, Ito K, Aizawa K , et al. Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia[J]. PLoS One, 2014,9(8):e104863. doi: 10.1371/journal.pone.0104863 URL pmid: 25111309
[36]	Shindo T, Ito K, Ogata T , et al. Low-intensity pulsed ultrasound enhances angiogenesis and ameliorates left ventricular dysfunction in a mouse model of acute myocardial infarction[J]. Arterioscler Thromb Vasc Biol, 2016,36(6):1220-1229. doi: 10.1161/ATVBAHA.115.306477 URL pmid: 27079882
[37]	Heffner MA, Anderson MJ, Yeh GC , et al. Altered bone development in a mouse model of peripheral sensory nerve inactivation[J]. J Musculoskelet Neuronal Interact, 2014,14(1):1-9. URL pmid: 24583535
[38]	杨博, 吴庆庆, 张亮 , 等. 低频脉冲超声对失下牙槽神经后下颌骨病理改变修复的影响[J]. 中国医学科学院学报, 2017,39(2):215-224.
	Yang B, Wu QQ, Zhang L , et al. Effect of low-intensity pulsed ultrasound on the mandibular remodeling following inferior alveolar nerve transection[J]. Acta Acad Med Sinic, 2017,39(2):215-224.
[39]	Jiang WL, Wang YX, Tang J , et al. Low-intensity pulsed ultrasound treatment improved the rate of autograft peripheral nerve regeneration in rat[J]. Sci Rep, 2016,6:22773. doi: 10.1038/srep22773 URL pmid: 27102358
[40]	Lv Y, Nan PP, Chen GB , et al. In vivo repair of rat transected sciatic nerve by low-intensity pulsed ultrasound and induced pluripotent stem cells-derived neural crest stem cells[J]. Biotechnol Lett, 2015,37(12):2497-2506. doi: 10.1007/s10529-015-1939-5 URL pmid: 26303432
[41]	Xia B, Chen GB, Zou Y , et al. Low-intensity pulsed ultrasound combination with induced pluripotent stem cells-derived neural crest stem cells and growth differentiation factor 5 promotes sciatic nerve regeneration and functional recovery[J]. J Tissue Eng Regen Med, 2019,13(4):625-636. doi: 10.1002/term.2823 URL pmid: 30770650
[42]	Zhang H, Lin X, Wan H , et al. Effect of low-intensity pulsed ultrasound on the expression of neurotrophin-3 and brain-derived neurotrophic factor in cultured Schwann cells[J]. Microsurgery, 2009,29(6):479-485. doi: 10.1002/micr.20644 URL pmid: 19308950
[43]	Zhou XY, Xu XM, Wu SY , et al. Low-intensity pulsed ultrasound-induced spinal fusion is coupled with enhanced calcitonin gene-related peptide expression in rat model[J]. Ultrasound Med Biol, 2017,43(7):1486-1493. doi: 10.1016/j.ultrasmedbio.2017.03.012 URL pmid: 28457632
[44]	Lam WL, Guo X, Leung KS , et al. The role of the sensory nerve response in ultrasound accelerated fracture repair[J]. J Bone Joint Surg Br, 2012,94(10):1433-1438. doi: 10.1302/0301-620X.94B10.29139 URL pmid: 23015574