Top

Published in:

01-02-2015 | Original Article

Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate

Authors: Jae-Yeol Lee, In-Ryoung Kim, Bong-Soo Park, Yong-Deok Kim, In-Kyo Chung, Jae-Min Song, Sang-Hun Shin

Published in: Lasers in Medical Science | Issue 2/2015

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy. However, its pathophysiology is not yet fully elucidated, and effective treatment of BRONJ remains unclear. The aim of this study is to investigate the effects of alendronate on oral keratinocytes and of low-level laser therapy (LLLT) on alendronate-treated keratinocytes, specifically by evaluating their viability, apoptosis, and wound healing function after irradiation. Oral keratinocyte cells (HaCaT) were exposed to 25 μM alendronate. Then, laser irradiation was performed with a low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; NDLux, Seoul, Korea) using 1.2 J/cm² energy dose. Viability was analyzed using MTT assay. Apoptosis was measured by Hoechst staining, caspase assay. Changes in secretion of IL-8, VEGF, and collagen type I were studied by ELISA and immunofluorescence microscopy. Scratch wound assays were also performed to measure cellular migration. Our results show that alendronate inhibits keratinocyte viability, expression of IL-8, VEGF, and collagen type I which are intimately related to healing events and cell migration while promoting apoptosis. Our results serve to demonstrate the utility of LLLT in partially overcoming the inhibitory effects of this bisphosphonate. From these results, the authors believe that the present study will provide an experimental basis for a fuller explanation of the clinical effects of LLLT as a BRONJ treatment modality.

Silverman SL, Maricic M (2007) Recent developments in bisphosphonate therapy. Semin Arthritis and Rheum 37:1–12CrossRef

Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1238–1239CrossRef

Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534PubMedCrossRef

Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567–1575PubMedCrossRef

Walter C, Pabst A, Ziebart T, Klein M, Al-Nawas B (2011) Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis 17:194–199PubMedCrossRef

Scheper MA, Badros A, Chaisuparat R, Cullen KJ, Meiller TF (2009) Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. Br J Haematol 144:667–676PubMedCentralPubMedCrossRef

Ravosa MJ, Ning J, Liu Y, Stack MS (2011) Bisphosphonate effects on the behaviour of oral epithelial cells and oral fibroblasts. Arch Oral Biol 56:491–498PubMedCrossRef

Landersberg R, Cozin M, Creamrs S, Woo V, Kousteni S, Sinha S, Garrett-Sinha L, Raghavan S (2008) Inhibition of oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 66:839–847CrossRef

Reid IR, Bolland MJ, Grey AB (2007) Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity? Bone 41:318–320PubMedCrossRef

10.

Marx RE, Cillo JE Jr, Ulloa JJ (2007) Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg 65:2397–2410PubMedCrossRef

11.

Abu-Id MH, Açil Y, Gottschalk J, Kreusch T (2006) Bisphosphonate-associated osteonecrosis of the jaw. Mund Kiefer Gesichtschir 10:73–81PubMedCrossRef

12.

Abramoff MM, Lopes NN, Lopes LA, Dib LL, Guilherme A, Caran EM, Barreto AD, Lee ML, Petrilli AS (2008) Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients. Photomed Laser Surg 26:393–400PubMedCrossRef

13.

Marques MM, Pereira AN, Fujihara NA, Nogueira FN, Eduardo CP (2004) Effect of low-power laser irradiation on protein synthesis and ultrastructure of human gingival fibroblasts. Lasers Surg Med 34:260–265PubMedCrossRef

14.

Damante CA, De Micheli G, Miyagi SP, Feist IS, Marques MM (2009) Effect of laser phototherapy on the release of fibroblast growth factors by human gingival fibroblasts. Lasers Med Sci 24:885–891PubMedCrossRef

15.

Scoletta M, Arduino PG, Reggio L, Dalmasso P, Mozzati M (2010) Effect of low-level laser irradiation on bisphosphonate-induced osteonecrosis of the jaws: preliminary results of a prospective study. Photomed Laser Surg 28:179–184PubMedCrossRef

16.

Bayram H, Kenar H, Taşar F, Hasırcı V (2013) Effect of low level laser therapy and zoledronate on the viability and ALP activity of Saos-2 cells. Int J Oral Maxillofac Surg 42:140–146PubMedCrossRef

17.

Borromeo GL, Tsao CE, Darby IB, Ebeling PR (2011) A review of the clinical implications of bisphosphonates in dentistry. Aust Dent J 56:2–9PubMedCrossRef

18.

de Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang KK (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335:1016–1021PubMedCrossRef

19.

Marshall JK, Thabane M, James C (2006) Randomized active and placebo-controlled endoscopy study of a novel protected formulation of oral alendronate. Dig Dis Sci 51:864–868PubMedCrossRef

20.

Rubegni P, Fimiani M (2006) Images in clinical medicine. Bisphosphonate-associated contact stomatitis. N Engl J Med 355:e25PubMedCrossRef

21.

Landesberg R, Woo V, Cremers S, Cozin M, Marolt D, Vunjak-Novakovic G, Kousteni S, Raghavan S (2011) Potential pathophysiological mechanisms in osteonecrosis of the jaw. Ann N Y Acad Sci 1218:62–79PubMedCrossRef

22.

Kim RH, Lee RS, Williams D, Bae S, Woo J, Lieberman M, Oh JE, Dong Q, Shin KH, Kang MK, Park NH (2011) Bisphosphonates induce senescence in normal human oral keratinocytes. J Dent Res 90:810–816PubMedCentralPubMedCrossRef

23.

Ohnuki H, Izumi K, Terada M, Saito T, Kato H, Suzuki A, Kawano Y, Nozawa-Inoue K, Takagi R, Maeda T (2012) Zoledronic acid induces S-phase arrest via a DNA damage response in normal human oral keratinocytes. Arch Oral Biol 57:906–917PubMedCrossRef

24.

Santoro MM, Gaudino G (2005) Cellular and molecular facets of keratinocyte reepithelization during wound healing. Exp Cell Res 304:274–286PubMedCrossRef

25.

Eming SA, Brachvogel B, Odorisio T, Koch M (2007) Regulation of angiogenesis: wound healing as a model. Prog Histochem Cytochem 42:115–170PubMedCrossRef

26.

Pabst AM, Ziebart T, Koch FP, Taylor KY, Al-Nawas B, Walter C (2012) The influence of bisphosphonates on viability, migration, and apoptosis of human oral keratinocytes-in vitro study. Clin Oral Investig 16:87–93PubMedCrossRef

27.

Scheller EL, Baldwin CM, Kuo S, D’Silva NJ, Feinberg SE, Krebsbach PH, Edwards PC (2011) Bisphosphonates inhibit expression of p63 by oral keratinocytes. J Dent Res 90:894–899PubMedCentralPubMedCrossRef

28.

Häkkinen L, Uitto VJ, Larjava H (2000) Cell biology of gingival wound healing. Periodontol 24:127–152CrossRef

29.

Werner S, Krieg T, Smola H (2007) Keratinocyte–fibroblast interactions in wound healing. J Invest Dermatol 127:998–1008PubMedCrossRef

30.

Goldman L, Goldman B, Van Lieu N (1987) Current laser dentistry. Lasers Surg Med 6:559–562PubMedCrossRef

31.

Ohshiro T, Fujino T (1993) Laser applications in plastic and reconstructive surgery. Keio J Med 42:191–195PubMedCrossRef

32.

Nanami T, Shiba H, Ikeuchi S, Nagai T, Asanami S, Shibata T (1993) Clinical applications and basic studies of laser in dentistry and oral surgery. Keio J Med 42:199–201PubMed

33.

Haas AF, Isseroff RR, Wheeland RG, Rood PA, Graves PJ (1990) Low-energy helium-neon laser irradiation increases the motility of cultured human keratinocytes. J Invest Dermatol 94:822–826PubMedCrossRef

34.

Basso FG, Oliveira CF, Kurachi C, Hebling J, Costa CA (2013) Biostimulatory effect of low-level laser therapy on keratinocytes in vitro. Lasers Med Sci 28:367–374PubMedCrossRef

35.

Karu TI, Pyatibrat LV, Kolyakov SF, Afanasyeva NI (2005) Absorption measurements of a cell monolayer relevant to phototherapy: reduction of cytochrome c oxidase under near IR radiation. J Photochem Photobiol B 81:98–106PubMedCrossRef

36.

Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT (2003) Therapeutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci U S A 100:3439–3444PubMedCentralPubMedCrossRef

37.

Shefer G, Oron U, Irintchev A, Wernig A, Halevy O (2001) Skeletal muscle cell activation by low-energy laser irradiation: a role for the MAPK/ERK pathway. J Cell Physiol 187:73–80PubMedCrossRef

38.

Zhang L, Xing D, Gao X, Wo S (2009) Low-power laser irradiation promotes cell proliferation by activating PI3K/Akt pathway. J Cell Physiol 219:553–562PubMedCrossRef

39.

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 28:543–550PubMedCrossRef

40.

Dadpay M, Sharifian Z, Bayat M, Bayat M, Dabbagh A (2012) Effects of pulsed infra-red low level-laser irradiation on open skin wound healing of healthy and streptozotocin-induced diabetic rats by biomechanical evaluation. J Photochem Photobiol B 111:1–8PubMedCrossRef

41.

Almeida-Lopes L, Rigau J, Zângaro RA, Guidugli-Neto J, Jaeger MM (2001) Comparison of the low level laser therapy effects on cultured human gingival fibroblasts proliferation using different irradiance and same fluence. Lasers Surg Med 29:179–184PubMedCrossRef

42.

Loevschall H, Arenholt-Bindslev D (1994) Effect of low level diode laser irradiation of human oral mucosa fibroblasts in vitro. Lasers Surg Med 14:347–354PubMedCrossRef

43.

Atsushi E, Korenori O, Satoshi I, Ebisu S, Nakano T, Umakoshi Y (2003) Effects of a-TCP and TetCP on MC3T3-E1 proliferation, differentiation and mineralization. Biomaterials 24:831–836CrossRef

44.

Beck GR Jr, Sullivan EC, Moran E, Zerler B (1998) Relationship between alkaline phosphatase levels, osteopontin expression, and mineralization in differentiating MC3T3-E1 osteoblasts. J Cell Biochem 68:269–280PubMedCrossRef

45.

Bossini PS, Rennó AC, Ribeiro DA, Fangel R, Ribeiro AC, Lahoz Mde A, Parizotto NA (2012) Low level laser therapy (830 nm) improves bone repair in osteoporotic rats: similar outcomes at two different dosages. Exp Gerontol 47:136–142PubMedCrossRef

Title: Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate
Authors: Jae-Yeol Lee
In-Ryoung Kim
Bong-Soo Park
Yong-Deok Kim
In-Kyo Chung
Jae-Min Song
Sang-Hun Shin
Publication date: 01-02-2015
Publisher: Springer London
Published in: Lasers in Medical Science / Issue 2/2015
Print ISSN: 0268-8921
Electronic ISSN: 1435-604X
DOI: https://doi.org/10.1007/s10103-013-1382-6

2024 ASCO Annual Meeting

Springer Medicine

Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2015

Effects of low-level laser therapy on orthodontics: rate of tooth movement, pain, and release of RANKL and OPG in GCF

Clinical evaluation of low-power laser and a desensitizing agent on dentin hypersensitivity

Effect of optical clearing agents on optical coherence tomography images of cervical epithelium

Labial frenectomy with Nd:YAG laser and conventional surgery: a comparative study

Effectiveness of a new method of disinfecting the root canal, using Er, Cr:YSGG laser to kill Enterococcus faecalis in an infected tooth model

Antimicrobial photodynamic therapy against pathogenic bacterial suspensions and biofilms using chloro-aluminum phthalocyanine encapsulated in nanoemulsions