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Effects of low-level laser therapy on the expression of osteogenic genes during the initial stages of bone healing in rats: a microarray analysis

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Abstract

This study evaluated the morphological changes produced by LLLT on the initial stages of bone healing and also studied the pathways that stimulate the expression of genes related to bone cell proliferation and differentiation. One hundred Wistar rats were divided into control and treated groups. Noncritical size bone defects were surgically created at the upper third of the tibia. Laser irradiation (Ga-Al-As laser 830 nm, 30 mW, 94 s, 2.8 J) was performed for 1, 2, 3, 5, and 7 sessions. Histopathology revealed that treated animals produced increased amount of newly formed bone at the site of the injury. Moreover, microarray analysis evidenced that LLLT produced a significant increase in the expression TGF-β, BMP, FGF, and RUNX-2 that could stimulate osteoblast proliferation and differentiation, which may be related to improving the deposition of newly formed bone at the site of the injury. Thus, it is possible to conclude that LLLT improves bone healing by producing a significant increase in the expression of osteogenic genes.

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References

  1. Sella VR, do Bomfim FR, Machado PC, da Silva Morsoleto MJ, Chohfi M, Plapler H (2015) Effect of low-level laser therapy on bone repair: a randomized controlled experimental study. Lasers Med Sci. [Epub ahead of print]

  2. Claes L, Willie B (2007) The enhancement of bone regeneration by ultrasound. Prog Biophys Mol Biol 93:384–98

    Article  PubMed  Google Scholar 

  3. Einhorn TA, Gerstenfeld LC (2015) Fracture healing: mechanisms and interventions. Nat Rev Rheumatol 11(1):45–54

    Article  PubMed Central  PubMed  Google Scholar 

  4. Hoppe A, Güldal NS, Boccaccini AR (2011) A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. Biomaterials 32(11):2757–74

    Article  CAS  PubMed  Google Scholar 

  5. Rodrigues NC, Assis L, Fernandes KR, Magri A, Ribeiro DA, Brunelli R, Abreu DC, Renno AC (2013) Effects of 660 nm low-level laser therapy on muscle healing process after cryolesion. J Rehabil Res Dev 50(7):985–96

    Article  PubMed  Google Scholar 

  6. Carrinho PM, Renno AC, Koeke P, Salate AC, Parizotto NA, Vidal BC (2006) Comparative study using 685-nm and 830-nm lasers in the tissue repair of tenotomized tendons in the mouse. Photomed Laser Surg 24:754–8

    Article  PubMed  Google Scholar 

  7. Oliveira P, Santos AA, Rodrigues T, Tim CR, Pinto KZ, Magri AM, Fernandes KR, Mattiello SM, Parizotto NA, Anibal FF, Rennó AC (2013) Effects of phototherapy on cartilage structure and inflammatory markers in an experimental model of osteoarthritis. J Biomed Opt 18:128004

    Article  PubMed  Google Scholar 

  8. Bossini PS, C, Ribeiro DA, Fangel R, C, Lahoz M De A, Parizotto NA (2012) Low level laser therapy (830nm) improves bone repair in osteoporotic rats: similar outcomes at two different dosages. Exp Gerontol 2:136–142

  9. Tim CR, Pinto KN, Rossi BR, Fernandes K, Matsumoto MA, Parizotto NA, Rennó AC (2014) Low-level laser therapy enhances the expression of osteogenic factors during bone repair in rats. Lasers Med Sci 1:147–56

    Article  Google Scholar 

  10. Karu TI, Piatibrat LV, Kalendo GS (1999) Suppression of the intracellular concentration of ATP by irradiating with a laser pulse of wavelength lambda = 820 nm. Dokl Akad Nauk 364:399–401

    CAS  PubMed  Google Scholar 

  11. Buravlev EA, Zhidkova TV, Osipov AN, Vladimirov YA (2015) Are the mitochondrial respiratory complexes blocked by NO the targets for the laser and LED therapy? Lasers Med Sci 30:173–80

    Article  PubMed  Google Scholar 

  12. Stein A, Benayahu D, Maltz L, Oron U (2005) Low-level laser irradiation promotes proliferation and differentiation of human osteoblasts in vitro. Photomed Laser Surg 23:161–6

    Article  CAS  PubMed  Google Scholar 

  13. Fávaro-Pípi E, Ribeiro DA, Ribeiro JU, Bossini P, Oliveira P, Parizotto NA, Tim C, de Araújo HS, Renno AC (2011) Low-level laser therapy induces differential expression of osteogenic genes during bone repair in rats. Photomed Laser Surg 29:311–7

    Article  PubMed  Google Scholar 

  14. Wu YH, Wang J, Gong DX, Gu HY, Hu SS, Zhang H (2012) Effects of low-level laser irradiation on mesenchymal stem cell proliferation: a microarray analysis. Lasers Med Sci 27:509–19

    Article  PubMed  Google Scholar 

  15. Laraia EM, Silva IS, Pereira DM, Dos Reis FA, Albertini R, De Almeida P, Leal Junior EC, De Tarso Camillo De Carvalho P (2012) Effect of low-level laser therapy (660 nm) on acute inflammation induced by tenotomy of Achilles tendon in rats. Photochem Photobiol 88:1546–50

    Article  CAS  PubMed  Google Scholar 

  16. de Lima FM, Villaverde AB, Albertini R, Corrêa JC, Carvalho RL, Munin E, Araújo T, Silva JA, Aimbire F (2011) Dual Effect of low-level laser therapy (LLLT) on the acute lung inflammation induced by intestinal ischemia and reperfusion: action on anti- and pro-inflammatory cytokines. Lasers Surg Med 43:410–20

    Article  PubMed  Google Scholar 

  17. Garavello I, Baranauskas V, da Cruz-Höfling MA (2004) The effects of low laser irradiation on angiogenesis in injured rat tibiae. Histol Histopathol 19(1):43–8

    CAS  PubMed  Google Scholar 

  18. Assis L, Moretti AI, Abrahão TB, Cury V, Souza HP, Hamblin MR, Parizotto NA (2012) Low-level laser therapy (808 nm) reduces inflammatory response and oxidative stress in rat tibialis anterior muscle after cryolesion. Lasers Surg Med 44:726–35

    Article  PubMed Central  PubMed  Google Scholar 

  19. da Silva AP, Petri AD, Crippa GE, Stuani AS, Stuani AS, Rosa AL, Stuani MB (2012) Effect of low-level laser therapy after rapid maxillary expansion on proliferation and differentiation of osteoblastic cells. Lasers Med Sci 27:777–83

    Article  PubMed  Google Scholar 

  20. de Castro PA, Savoldi M, Bonatto D, Malavazi I, Goldman MH, Berretta AA, Goldman GH (2012) Transcriptional profiling of Saccharomyces cerevisiae exposed to propolis. BMC Complement Altern Med 24:194

    Article  Google Scholar 

  21. Soleimani M, Abbasnia E, Fathi M, Sahraei H, Fathi Y, Kaka G (2012) 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 27:423–30

    Article  PubMed  Google Scholar 

  22. Medina-Huertas R, Manzano-Moreno FJ, De Luna-Bertos E, Ramos-Torrecillas J, García-Martínez O, Ruiz C. The effects of low-level diode laser irradiation on differentiation, antigenic profile, and phagocytic capacity of osteoblast-like cells (MG-63). Lasers Med Sci 29:1479–1484

  23. Matsumoto MA, Ferino FV, Monteleone GF, Ribeiro DA (2009) Low level laser therapy modulates cyclo-oxygenase-2 expression during bone repair in rats. Lasers Med Sci 24:196–201

    Article  Google Scholar 

  24. Altan AB, Bicakci AA, Avunduk MC, Esen H (2015) The effect of dosage on the efficiency of LLLT in new bone formation at the expanded suture in rats. Lasers Med Sci 30:255–62

    Article  PubMed  Google Scholar 

  25. Kulterer B, Friedl G, Jandrositz A, Sanchez-Cabo F, Prokesch A, Paar C, Scheideler M, Windhager R, Preisegger KH, Trajanoski Z (2007) Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. BMC Genomics 12:8–70

    Google Scholar 

  26. Li WG, Xu XX (2005) The expression of N-cadherin, fibronectin during chondrogenic differentiation of MSC induced by TGF-beta(1). Chin J Traumatol 8:349–51

    PubMed  Google Scholar 

  27. Pyo SJ, Song WW, Kim IR, Park BS, Kim CH, Shin SH, Chung IK, Kim YD (2013) Low-level laser therapy induces the expressions of BMP-2, osteocalcin, and TGF-β1 in hypoxic-cultured human osteoblasts. Lasers Med Sci 2:543–50

    Article  Google Scholar 

  28. Chen MH, Huang YC, Sun JS, Chao YH, Chen MH (2014) Second messengers mediating the proliferation and collagen synthesis of tenocytes induced by low-level laser irradiation. Lasers Med Sci 30:263–72

    Article  PubMed  Google Scholar 

  29. Bessa PC, Casal M, Reis RL (2008) Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med 2:1–13

    Article  CAS  PubMed  Google Scholar 

  30. Reddi AH (2001) Bone morphogenetic proteins: from basic science to clinical applications. J Bone Joint Surg 83-A:S1–6

    PubMed  Google Scholar 

  31. Kloen P, Di Paola M, Borens O, Richmond J, Perino G, Helfet DL, Goumans MJ (2003) BMP signaling components are expressed in human fracture callus. Bone 33:362–71

    Article  CAS  PubMed  Google Scholar 

  32. Ducy P (2000) Cbfa1: a molecular switch in osteoblast biology. Dev Dyn 219:461–71

    Article  CAS  PubMed  Google Scholar 

  33. Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24:218–35

    Article  CAS  PubMed  Google Scholar 

  34. McGee-Lawrence ME, Li X, Bledsoe KL, Wu H, Hawse JR, Subramaniam M, Razidlo DF, Stensgard BA, Stein GS, van Wijnen AJ, Lian JB, Hsu W, Westendorf JJ (2013) Runx2 protein repress Axin2 expression in osteoblasts and is required for cranio synostosis in Axin2-deficient mice. J Biol Chem 288:5291–302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Derynck R, Miyazono K (2008) The TGF-β Family. Cold Spring Harbor, New York

    Google Scholar 

  36. Komori T (2006) Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99:1233–9

    Article  CAS  PubMed  Google Scholar 

  37. Mendelson A, Frank E, Allred C, Jones E, Chen M, Zhao W, Mao JJ (2011) Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro. FASEB J 25:3496–504

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Bar I, Zilberman Y, Zeira E, Galun E, Honigman A, Turgeman G, Clemens T, Gazit Z, Gazit D (2003) Molecular imaging of the skeleton: quantitative real-time bioluminescence monitoring gene expression in bone repair and development. J Bone Miner Res 18:570–8

    Article  CAS  Google Scholar 

  39. Cantatore FP, Corrado A, Grano M, Quarta L, Colucci S, Melillo N (2004) Osteocalcin synthesis by human osteoblasts from normal and osteoarthritic bone after vitamin D3 stimulation. Clin Rheumatol 23:490–5

    Article  PubMed  Google Scholar 

  40. Fernandes KR, Ribeiro DA, Rodrigues NC, Tim C, Santos AA, Parizotto NA, De Araujo HS, Driusso P, Rennó AC (2013) Effects of low-level laser therapy on the expression of osteogenic genes related in the initial stages of bone defects in rats. J Biomed Opt 3:038002

    Article  Google Scholar 

  41. Stein E, Koehn J, Sutter W, Wendtlandt G, Wanschitz F, Thurnher D, Baghestanian M, Turhani D (2008) Initial effects of low-level laser therapy on growth and differentiation of human osteoblast-like cells. Wien Klin Wochenschr 120:112–7

    Article  CAS  PubMed  Google Scholar 

  42. Marie PJ (2003) Fibroblast growth factor signaling controlling osteoblast differentiation. Gene 316:23–32

    Article  CAS  PubMed  Google Scholar 

  43. Boden SD (2005) The ABCs of BMPs. Orthop Nurs 24:49–52

    Article  PubMed  Google Scholar 

  44. Saygun I, Nizam N, Ural AU, Serdar MA, Avcu F, Tözüm TF (2012) Low-level laser irradiation affects the release of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and receptor of IGF-I (IGFBP3) from osteoblasts. Photomed Laser Surg 30:149–54

    Article  CAS  PubMed  Google Scholar 

  45. Du X, Xie Y, Xian CJ, Chen L (2012) Role of FGFs/FGFRs in skeletal development and bone regeneration. J Cell Physiol 227:3731–43

    Article  CAS  PubMed  Google Scholar 

  46. Batista JD, Sargenti-Neto S, Dechichi P, Rocha FS, Pagnoncelli RM (2015) Low-level laser therapy on bone repair: is there any effect outside the irradiated field? Lasers Med Sci. 2015 May 15. [Epub ahead of print]

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Acknowledgments

We would like to acknowledge the contributions of Brazilian funding agency Fapesp and the Center for Computational Engineering and Sciences at UNICAMP SP Brazil (FAPESP/CEPID and project #2010/15335-0 and project #2013/08293-7) for the financial support of this research.

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None have been included in the manuscript.

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Authors and Affiliations

  1. Department of Physiotherapy, Federal University of São Carlos, Rod Washington Luis Km 235, São Carlos, 13565-905, Brazil

    Carla Roberta Tim, Hueliton Wilian Kido & Nivaldo Antonio Parizotto

  2. Department of Bioscience, Federal University of São Paulo, Av. Ana Costa 95, Santos, 11050-240, Brazil

    Paulo Sérgio Bossini & Ana Cláudia Rennó

  3. Department of Genetics and Evolution, Federal University of São Carlos, Rod Washington Luis Km 235, São Carlos, 13565-905, Brazil

    Iran Malavazi

  4. Department of Clinical Analysis, Toxicological and Bromatological, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café 95, Ribeirão Preto, 14049-900, Brazil

    Marcia Regina von Zeska Kress

  5. Department of Genetics and Evolution, State University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, 13083-970, Brazil

    Marcelo Falsarella Carazzolle

  6. Brazilian National Center for Research in Energy and Materials, Brazilian Biosciences National Laboratory, Giuseppe Máximo Scolfaro 10.000, Campinas, 13083-970, Brazil

    Marcelo Falsarella Carazzolle

Authors
  1. Carla Roberta Tim
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  2. Paulo Sérgio Bossini
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  6. Marcelo Falsarella Carazzolle
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  7. Nivaldo Antonio Parizotto
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  8. Ana Cláudia Rennó
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Correspondence to Carla Roberta Tim.

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Tim, C.R., Bossini, P.S., Kido, H.W. et al. Effects of low-level laser therapy on the expression of osteogenic genes during the initial stages of bone healing in rats: a microarray analysis. Lasers Med Sci 30, 2325–2333 (2015). https://doi.org/10.1007/s10103-015-1807-5

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  • DOI: https://doi.org/10.1007/s10103-015-1807-5

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