Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis
Tóm tắt
Bone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown. Mouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed. LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β. LLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.
Tài liệu tham khảo
Ahmad T, Byun H, Lee J, Madhurakat Perikamana SK, Shin YM, Kim EM, et al. Stem cell spheroids incorporating fibers coated with adenosine and polydopamine as a modular building blocks for bone tissue engineering. Biomaterials. 2020;230:119652. https://doi.org/10.1016/j.biomaterials.2019.119652.
Chou J, Hao J, Kuroda S, Ben-Nissan B, Milthopre B, Otsuka M. Bone regeneration of calvarial defect using marine calcareous-derived beta-tricalcium phosphate macrospheres. J Tiss Eng. 2014;5:2041731414523441.
Hjørting-Hansen E. Bone grafting to the jaws with special reference to reconstructive preprosthetic surgery. A historical review. Mund Kiefer Gesichtschir. 2002;6(1):6–14. https://doi.org/10.1007/s10006-001-0343-6.
Langer R, Vacanti JP. Tissue engineering. Science. 1993;260(5110):920–6. https://doi.org/10.1126/science.8493529.
Dimitriou R, Jones E, McGonagle D, Giannoudis PV. Bone regeneration: current concepts and future directions. BMC Med. 2011;9(1):66. https://doi.org/10.1186/1741-7015-9-66.
Rose FR, Oreffo RO. Bone tissue engineering: hope vs hype. Biochem Biophys Res Commun. 2002;292(1):1–7. https://doi.org/10.1006/bbrc.2002.6519.
Tomlinson RE, Silva MJ. Skeletal blood flow in bone repair and maintenance. Bone Res. 2013;1(4):311–22. https://doi.org/10.4248/BR201304002.
Pelissier P, Villars F, Mathoulin-Pelissier S, Bareille R, Lafage-Proust MH, Vilamitjana-Amedee J. Influences of vascularization and osteogenic cells on heterotopic bone formation within a madreporic ceramic in rats. Plast Reconstr Surg. 2003;111(6):1932–41. https://doi.org/10.1097/01.PRS.0000055044.14093.EA.
Percival CJ, Richtsmeier JT. Angiogenesis and intramembranous osteogenesis. Dev Dyn. 2013;242(8):909–22. https://doi.org/10.1002/dvdy.23992.
Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med. 1999;5(6):623–8. https://doi.org/10.1038/9467.
Peng Y, Wu S, Li Y, Crane JL. Type H blood vessels in bone modeling and remodeling. Theranostics. 2020;10(1):426–36. https://doi.org/10.7150/thno.34126.
Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323–8. https://doi.org/10.1038/nature13145.
le Noble F, le Noble J. Bone biology: Vessels of rejuvenation. Nature. 2014;507(7492):313–4. https://doi.org/10.1038/nature13210.
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16(9):4604–13. https://doi.org/10.1128/MCB.16.9.4604.
Tang N, Wang L, Esko J, Giordano FJ, Huang Y, Gerber HP, et al. Loss of HIF-1alpha in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell. 2004;6(5):485–95. https://doi.org/10.1016/j.ccr.2004.09.026.
Amid R, Kadkhodazadeh M, Ahsaie MG, Hakakzadeh A. Effect of low level laser therapy on proliferation and differentiation of the cells contributing in bone regeneration. J Lasers Med Sci. 2014;5(4):163–70.
Bayat M, Virdi A, Jalalifirouzkouhi R, Rezaei F. Comparison of effects of LLLT and LIPUS on fracture healing in animal models and patients: a systematic review. Prog Biophys Mol Biol. 2018;132:3–22. https://doi.org/10.1016/j.pbiomolbio.2017.07.004.
Priglinger E, Maier J, Chaudary S, Lindner C, Wurzer C, Rieger S, et al. Photobiomodulation of freshly isolated human adipose tissue-derived stromal vascular fraction cells by pulsed light-emitting diodes for direct clinical application. J Tissue Eng Regen Med. 2018;12(6):1352–62. https://doi.org/10.1002/term.2665.
Yamauchi N, Taguchi Y, Kato H, Umeda M. High-power, red-light-emitting diode irradiation enhances proliferation, osteogenic differentiation, and mineralization of human periodontal ligament stem cells via ERK signaling pathway. J Periodontol. 2018;89(3):351–60. https://doi.org/10.1002/JPER.17-0365.
Sarvestani FK, Dehno NS, Nazhvani SD, Bagheri MH, Abbasi S, Khademolhosseini Y, et al. Effect of low-level laser therapy on fracture healing in rabbits. Laser Ther. 2017;26(3):189–93. https://doi.org/10.5978/islsm.17-OR-14.
Escudero JSB, Perez MGB, de Oliveira Rosso MP, Buchaim DV, Pomini KT, Campos LMG, et al. Photobiomodulation therapy (PBMT) in bone repair: a systematic review. Injury. 2019;50(11):1853–67. https://doi.org/10.1016/j.injury.2019.09.031.
Chen C, Yan S, Qiu S, Geng Z, Wang Z. HIF/Ca(2+)/NO/ROS is critical in roxadustat treating bone fracture by stimulating the proliferation and migration of BMSCs. Life Sci. 2021;264:118684. https://doi.org/10.1016/j.lfs.2020.118684.
Migliario M, Pittarella P, Fanuli M, Rizzi M, Renò F. Laser-induced osteoblast proliferation is mediated by ROS production. Lasers Med Sci. 2014;29(4):1463–7. https://doi.org/10.1007/s10103-014-1556-x.
Arany PR, Cho A, Hunt TD, Sidhu G, Shin K, Hahm E, et al. Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Sci Transl Med. 2014;6:238ra69.
Yang Z, Mu Z, Dabovic B, Jurukovski V, Yu D, Sung J, et al. Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J Cell Biol. 2007;176(6):787–93. https://doi.org/10.1083/jcb.200611044.
Wang L, Wu F, Liu C, Song Y, Guo J, Yang Y, et al. Low-level laser irradiation modulates the proliferation and the osteogenic differentiation of bone marrow mesenchymal stem cells under healthy and inflammatory condition. Lasers Med Sci. 2019;34(1):169–78. https://doi.org/10.1007/s10103-018-2673-8.
Zhu H, Guo ZK, Jiang XX, Li H, Wang XY, Yao HY, et al. A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone. Nat Protoc. 2010;5(3):550–60. https://doi.org/10.1038/nprot.2009.238.
Hankenson KD, Dishowitz M, Gray C, Schenker M. Angiogenesis in bone regeneration. Injury. 2011;42(6):556–61. https://doi.org/10.1016/j.injury.2011.03.035.
Schipani E, Maes C, Carmeliet G, Semenza GL. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res. 2009;24(8):1347–53. https://doi.org/10.1359/jbmr.090602.
Balogh E, Tóth A, Méhes G, Trencsényi G, Paragh G, Jeney V. Hypoxia triggers osteochondrogenic differentiation of vascular smooth muscle cells in an HIF-1 (hypoxia-inducible factor 1)-dependent and reactive oxygen species-dependent manner. Arterioscler Thromb Vasc Biol. 2019;39(6):1088–99. https://doi.org/10.1161/ATVBAHA.119.312509.
Carvalho MS, Silva JC, Cabral JMS, da Silva CL, Vashishth D. Cultured cell-derived extracellular matrices to enhance the osteogenic differentiation and angiogenic properties of human mesenchymal stem/stromal cells. J Tissue Eng Regen Med. 2019;13(9):1544–58. https://doi.org/10.1002/term.2907.
Han HS, Jun I, Seok HK, Lee KS, Lee K, Witte F, et al. Biodegradable magnesium alloys promote angio-osteogenesis to enhance bone repair. Adv Sci. 2020;7:2000800.
Zhu S, Bennett S, Kuek V, Xiang C, Xu H, Rosen V, et al. Endothelial cells produce angiocrine factors to regulate bone and cartilage via versatile mechanisms. Theranostics. 2020;10(13):5957–65. https://doi.org/10.7150/thno.45422.
Zhang J, Pan J, Jing W. Motivating role of type H vessels in bone regeneration. Cell Prolif. 2020;53:e12874.
Li Y, Xu Q, Shi M, Gan P, Huang Q, Wang A, et al. Low-level laser therapy induces human umbilical vascular endothelial cell proliferation, migration and tube formation through activating the PI3K/Akt signaling pathway. Microvasc Res. 2020;129:103959. https://doi.org/10.1016/j.mvr.2019.103959.
Chen CH, Hung HS, Hsu SH. Low-energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway. Lasers Surg Med. 2008;40(1):46–54. https://doi.org/10.1002/lsm.20589.
Moon JH, Rhee YH, Ahn JC, Kim B, Lee SJ, Chung PS. Enhanced survival of ischemic skin flap by combined treatment with bone marrow-derived stem cells and low-level light irradiation. Lasers Med Sci. 2018;33(1):1–9. https://doi.org/10.1007/s10103-017-2312-9.
Iryanov YM. Influence of laser irradiation low intensity on reparative osteogenesis and angiogenesis under transosseous osteosynthesis. J Lasers Med Sci. 2016;7(3):134–8. https://doi.org/10.15171/jlms.2016.23.
Mussttaf RA, Jenkins DFL, Jha AN. Assessing the impact of low level laser therapy (LLLT) on biological systems: a review. Int J Radiat Biol. 2019;95(2):120–43. https://doi.org/10.1080/09553002.2019.1524944.
Hopkins JT, McLoda TA, Seegmiller JG, David BG. Low-level laser therapy facilitates superficial wound healing in humans: A triple-blind, sham-controlled study. J Athl Train. 2004;39(3):223–9.
Garcia VG, Sahyon AS, Longo M, Fernandes LA, Gualberto Junior EC, Novaes VC, et al. Effect of LLLT on autogenous bone grafts in the repair of critical size defects in the calvaria of immunosuppressed rats. J Craniomaxillofac Surg. 2014;42(7):1196–202. https://doi.org/10.1016/j.jcms.2014.02.008.
Carrinho PM, Renno AC, Koeke P, Salate AC, Parizotto NA, Vidal BC. Comparative study using 685-nm and 830-nm lasers in the tissue repair of tenotomized tendons in the mouse. Photomed Laser Surg. 2006;24(6):754–8. https://doi.org/10.1089/pho.2006.24.754.
AlGhamdi KM, Kumar A, Moussa NA. Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells. Lasers Med Sci. 2012;27(1):237–49. https://doi.org/10.1007/s10103-011-0885-2.
Hirata S, Kitamura C, Fukushima H, Nakamichi I, Abiko Y, Terashita M, et al. Low-level laser irradiation enhances BMP-induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway. J Cell Biochem. 2010;111(6):1445–52. https://doi.org/10.1002/jcb.22872.
Soleimani M, Abbasnia E, Fathi M, Sahraei H, Fathi Y, Kaka G. The effects of low-level laser irradiation on differentiation and proliferation of human bone marrow mesenchymal stem cells into neurons and osteoblasts--an in vitro study. Lasers Med Sci. 2012;27(2):423–30. https://doi.org/10.1007/s10103-011-0930-1.
Xu C, Liu H, He Y, Li Y, He X. Endothelial progenitor cells promote osteogenic differentiation in co-cultured with mesenchymal stem cells via the MAPK-dependent pathway. Stem Cell Res Ther. 2020;11(1):537. https://doi.org/10.1186/s13287-020-02056-0.
He Y, Lin S, Ao Q, He X. The co-culture of ASCs and EPCs promotes vascularized bone regeneration in critical-sized bone defects of cranial bone in rats. Stem Cell Res Ther. 2020;11(1):338. https://doi.org/10.1186/s13287-020-01858-6.
Zaw SYM, Kaneko T, Zaw ZCT, Sone PP, Murano H, Gu B, et al. Crosstalk between dental pulp stem cells and endothelial cells augments angiogenic factor expression. Oral Dis. 2020;26:1275–83. https://doi.org/10.1111/odi.13341.
Sivaraj KK, Adams RH. Blood vessel formation and function in bone. Development. 2016;143(15):2706–15. https://doi.org/10.1242/dev.136861.
Salhotra A, Shah HN, Levi B, Longaker MT. Mechanisms of bone development and repair. Nat Rev Mol Cell Biol. 2020;21(11):696–711. https://doi.org/10.1038/s41580-020-00279-w.
Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis-dependent axis. Cell Metab. 2020;32:437–46.e5.
Mills EL, Kelly B, Logan A, Costa ASH, Varma M, Bryant CE, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell. 2016;167:457–70.e13.