OpenLB
Open Library of Bioscience
Advanced Search
Lasers in medical science
Jan 18, 2024;39 (1): 36.

Low-level laser therapy alleviates periodontal age-related inflammation in diabetic mice via the GLUT1/mTOR pathway.

Aimin Cui, Yuezhang Sun, Kangjian Zhu, Haonan Zou, Ziqi Yue, Yi Ding, Xiuxiu Song, Jiao Chen, Ning Ji, Qi Wang
Author Information
  1. Aimin Cui: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  2. Yuezhang Sun: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  3. Kangjian Zhu: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  4. Haonan Zou: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  5. Ziqi Yue: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  6. Yi Ding: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  7. Xiuxiu Song: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  8. Jiao Chen: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  9. Ning Ji: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
  10. Qi Wang: State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China. wqinno8751@gmail.com. ORCID
PMID: 38236306 DOI: 10.1007/s10103-024-03987-3

Abstract

Diabetes mellitus (DM) is a chronic age-related disease that was recently found as a secondary aging pattern regulated by the senescence associated secretory phenotype (SASP). The purpose of this study is to detect the potential efficacy and the specific mechanisms of low-level laser therapy (LLLT) healing of age-related inflammation (known as inflammaging) in diabetic periodontitis. Diabetic periodontitis (DP) mice were established by intraperitoneal streptozotocin (STZ) injection and oral P. gingivalis inoculation. Low-level laser irradiation (810 nm, 0.1 W, 398 mW/cm, 4 J/cm, 10 s) was applied locally around the periodontal lesions every 3 days for 2 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) stain was analyzed for periodontal soft tissue and alveolar bone. Western blots, immunohistochemistry, and immunofluorescence staining were used to evaluate the protein expression changes on SASP and GLUT1/mTOR pathway. The expression of aging-related factors and SASP including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were reduced in periodontal tissue of diabetic mice. The inhibitory effect of LLLT on GLUT1/mTOR pathway was observed by detecting the related factors mTOR, p-mTOR, GLUT1, and PKM2. COX, an intracytoplasmic photoreceptor, is a key component of the anti-inflammatory effects of LLLT. After LLLT treatment a significant increase in COX was observed in macrophages in the periodontal lesion. Our findings suggest that LLLT may regulate chronic low-grade inflammation by modulating the GLUT1/mTOR senescence-related pathway, thereby offering a potential treatment for diabetic periodontal diseases.

Keywords

Cytochrome c oxidase Hyperglycemia Inflammatory senescence Periodontal disease Photobiomodulation therapy Senescence-associated secretory phenotype

References

  1. Sun H (2022) IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 183:109119 [DOI: 10.1016/j.diabres.2021.109119]
  2. Löe H (1993) Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care 16:329–334 [DOI: 10.2337/diacare.16.1.329]
  3. Lakschevitz F, Aboodi G, Tenenbaum H, Glogauer M (2011) Diabetes and periodontal diseases: interplay and links. CDR 7:433–439. https://doi.org/10.2174/157339911797579205 [DOI: 10.2174/157339911797579205]
  4. Prattichizzo F, De Nigris V, Spiga R et al (2018) Inflammageing and metaflammation: the yin and yang of type 2 diabetes. Ageing Res Rev 41:1–17. https://doi.org/10.1016/j.arr.2017.10.003 [DOI: 10.1016/j.arr.2017.10.003]
  5. Midha A, Pan H, Abarca C et al (2021) 10-Unique human and mouse β-cell senescence-associated secretory phenotype (SASP) reveal conserved signaling pathways and heterogeneous factors. Diabetes 70:1098–1116. https://doi.org/10.2337/db20-0553 [DOI: 10.2337/db20-0553]
  6. Ikegami K, Yamashita M, Suzuki M, et al (2023) Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue. Aging. https://doi.org/10.18632/aging.204569
  7. Chen Z, Haus JM, Chen L, et al (2022) Inhibition of CCL28/CCR10-mediated eNOS downregulation improves skin wound healing in the obesity-induced mouse model of type 2 diabetes. Diabetes db211108. https://doi.org/10.2337/db21-1108
  8. Yu S, Zhao X, Zhang Y et al (2022) Clinical effectiveness of adjunctive diode laser on scaling and root planing in the treatment of periodontitis: is there an optimal combination of usage mode and application regimen? A systematic review and meta-analysis. Lasers Med Sci 37:759–769. https://doi.org/10.1007/s10103-021-03412-z [DOI: 10.1007/s10103-021-03412-z]
  9. Ren C, McGrath C, Jin L et al (2017) The effectiveness of low-level laser therapy as an adjunct to non-surgical periodontal treatment: a meta-analysis. J Periodont Res 52:8–20. https://doi.org/10.1111/jre.12361 [DOI: 10.1111/jre.12361]
  10. Kinane DF, Stathopoulou PG, Papapanou PN (2017) Periodontal diseases. Nat Rev Dis Primers 3:17038. https://doi.org/10.1038/nrdp.2017.38 [DOI: 10.1038/nrdp.2017.38]
  11. Choung H-W, Lee S-H, Ham AR et al (2019) Effectiveness of low-level laser therapy with a 915 nm wavelength diode laser on the healing of intraoral mucosal wound: an animal study and a double-blind randomized clinical trial. Medicina 55:405. https://doi.org/10.3390/medicina55080405 [DOI: 10.3390/medicina55080405]
  12. Qadri T, Miranda L, Tuner J, Gustafsson A (2005) The short-term effects of low-level lasers as adjunct therapy in the treatment of periodontal inflammation. J Clin Periodontol 32:714–719. https://doi.org/10.1111/j.1600-051X.2005.00749.x [DOI: 10.1111/j.1600-051X.2005.00749.x]
  13. Mrasori S, Popovska M, Rusevska B et al (2021) Effects of low level laser therapy (LLLT) on serum values of interleukin 6 (IL-6) in patients with periodontitis and type 2 diabetes mellitus (T2DM). Acta Inform Med 29:59. https://doi.org/10.5455/aim.2021.29.59-64 [DOI: 10.5455/aim.2021.29.59-64]
  14. Silva DNA, Cruz NTS, Martins AA et al (2023) Probiotic Lactobacillus rhamnosus EM1107 prevents hyperglycemia, alveolar bone loss, and inflammation in a rat model of diabetes and periodontitis. J Periodontol 94:376–388. https://doi.org/10.1002/JPER.22-0262 [DOI: 10.1002/JPER.22-0262]
  15. Wang Q, Nie L, Zhao P et al (2021) Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging. Int J Oral Sci 13:11. https://doi.org/10.1038/s41368-021-00116-6 [DOI: 10.1038/s41368-021-00116-6]
  16. Magliano DJ, Chen L, Islam RM et al (2021) Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settings. Lancet Diabetes Endocrinol 9:203–211. https://doi.org/10.1016/S2213-8587(20)30402-2 [DOI: 10.1016/S2213-8587(20)30402-2]
  17. Preshaw PM, Alba AL, Herrera D et al (2012) Periodontitis and diabetes: a two-way relationship. Diabetologia 55:21–31. https://doi.org/10.1007/s00125-011-2342-y [DOI: 10.1007/s00125-011-2342-y]
  18. Ohsugi Y, Niimi H, Shimohira T et al (2020) In vitro cytological responses against laser photobiomodulation for periodontal regeneration. IJMS 21:9002. https://doi.org/10.3390/ijms21239002 [DOI: 10.3390/ijms21239002]
  19. Soi S, Bains VK, Srivastava R, Madan R (2021) Comparative evaluation of improvement in periodontal and glycemic health status of type 2 diabetes mellitus patients after scaling and root planing with or without adjunctive use of diode laser. Lasers Med Sci 36:1307–1315. https://doi.org/10.1007/s10103-021-03261-w [DOI: 10.1007/s10103-021-03261-w]
  20. Kreisler M, Kohnen W, Marinello C et al (2003) Antimicrobial efficacy of semiconductor laser irradiation on implant surfaces. Int J Oral Maxillofac Implants 18:706–711 [PMID: 14579959]
  21. Lee HS, Lee Y, Jeong U et al (2020) Transoral low-level laser therapy via a cylindrical device to treat oral ulcers in a rodent model. Lasers Surg Med 52:647–652. https://doi.org/10.1002/lsm.23203 [DOI: 10.1002/lsm.23203]
  22. Gururaj S, Shankar S, Parveen F et al (2022) Assessment of healing and pain response at mandibular third molar extraction sites with and without pre- and postoperative photobiomodulation at red and near-infrared wavelengths: a clinical study. J Pharm Bioall Sci 14:470. https://doi.org/10.4103/jpbs.jpbs_675_21 [DOI: 10.4103/jpbs.jpbs_675_21]
  23. Polak D, Sanui T, Nishimura F (2000) Shapira L (2020) Diabetes as a risk factor for periodontal disease—plausible mechanisms. Periodontol 83:46–58. https://doi.org/10.1111/prd.12298 [DOI: 10.1111/prd.12298]
  24. Shetty B, Divakar DD, Jameel AHA et al (2023) Effect of non-surgical periodontal therapy with adjunct photodynamic therapy on periodontal and glycemic statuses in prediabetic patients with periodontal disease. Photodiagn Photodyn Ther 42:103362. https://doi.org/10.1016/j.pdpdt.2023.103362 [DOI: 10.1016/j.pdpdt.2023.103362]
  25. Pulivarthi P, Chava V, Gunupati S (2022) Salivary tumor necrosis factor-alpha levels in periodontitis associated with diabetes mellitus after low level laser therapy as an adjunct to scaling and root planning: a randomized clinical trial. J Indian Soc Periodontol 26:236. https://doi.org/10.4103/jisp.jisp_150_21 [DOI: 10.4103/jisp.jisp_150_21]
  26. Preshaw PM, Foster N (2000) Taylor JJ (2007) Cross-susceptibility between periodontal disease and type 2 diabetes mellitus: an immunobiological perspective. Periodontol 45:138–157. https://doi.org/10.1111/j.1600-0757.2007.00221.x [DOI: 10.1111/j.1600-0757.2007.00221.x]
  27. Shultis WA, Weil EJ, Looker HC et al (2007) Effect of periodontitis on overt nephropathy and end-stage renal disease in type 2 diabetes. Diabetes Care 30:306–311. https://doi.org/10.2337/dc06-1184 [DOI: 10.2337/dc06-1184]
  28. Aoki A, Mizutani K, Schwarz F et al (2000) (2015) Periodontal and peri-implant wound healing following laser therapy. Periodontol 68:217–269. https://doi.org/10.1111/prd.12080 [DOI: 10.1111/prd.12080]
  29. Borgnakke WS, Anderson PF, Shannon C, Jivanescu A (2015) Is there a relationship between oral health and diabetic neuropathy? Curr Diab Rep 15:93. https://doi.org/10.1007/s11892-015-0673-7 [DOI: 10.1007/s11892-015-0673-7]
  30. Lalla E, Papapanou PN (2011) Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol 7:738–748. https://doi.org/10.1038/nrendo.2011.106 [DOI: 10.1038/nrendo.2011.106]
  31. Chen S, Zhou D, Liu O et al (2022) Cellular senescence and periodontitis: mechanisms and therapeutics. Biology 11:1419. https://doi.org/10.3390/biology11101419 [DOI: 10.3390/biology11101419]
  32. De Cecco M, Ito T, Petrashen AP et al (2019) L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature 566:73–78. https://doi.org/10.1038/s41586-018-0784-9 [DOI: 10.1038/s41586-018-0784-9]
  33. Barutta F, Bellini S, Durazzo M, Gruden G (2022) Novel insight into the mechanisms of the bidirectional relationship between diabetes and periodontitis. Biomedicines 10:178. https://doi.org/10.3390/biomedicines10010178 [DOI: 10.3390/biomedicines10010178]
  34. Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP (2019) Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol. https://doi.org/10.26402/jpp.2019.6.01
  35. Freemerman AJ, Johnson AR, Sacks GN et al (2014) Metabolic reprogramming of macrophages. J Biol Chem 289:7884–7896. https://doi.org/10.1074/jbc.M113.522037 [DOI: 10.1074/jbc.M113.522037]
  36. Zhang Z, Deng X, Liu Y et al (2019) PKM2, function and expression and regulation. Cell Biosci 9:52. https://doi.org/10.1186/s13578-019-0317-8 [DOI: 10.1186/s13578-019-0317-8]
  37. Tu C, Wang L, Wei L (2022) The role of PKM2 in diabetic microangiopathy. DMSO 15:1405–1412. https://doi.org/10.2147/DMSO.S366403 [DOI: 10.2147/DMSO.S366403]
  38. Grant MM (2021) Pyruvate kinase, inflammation and periodontal disease. Pathogens 10:784. https://doi.org/10.3390/pathogens10070784 [DOI: 10.3390/pathogens10070784]
  39. Hasan D, Gamen E, Abu Tarboush N et al (2018) PKM2 and HIF-1α regulation in prostate cancer cell lines. PLoS One 13:e0203745. https://doi.org/10.1371/journal.pone.0203745 [DOI: 10.1371/journal.pone.0203745]
  40. Abdelhalim NM, Abdelbasset WK, Alqahtani BA, Samhan AF (2020) Low-level laser therapy for diabetic dermopathy in patients with type 2 diabetes: a placebo controlled pilot study. J Lasers Med Sci 11:481–485. https://doi.org/10.34172/jlms.2020.75 [DOI: 10.34172/jlms.2020.75]
  41. Houreld NN (2015) Healing of diabetic ulcers using photobiomodulation. Photomed Laser Surg 33:237–239. https://doi.org/10.1089/pho.2015.9847 [DOI: 10.1089/pho.2015.9847]
  42. Albuquerque-Pontes GM, Vieira RDP, Tomazoni SS et al (2015) Effect of pre-irradiation with different doses, wavelengths, and application intervals of low-level laser therapy on cytochrome c oxidase activity in intact skeletal muscle of rats. Lasers Med Sci 30:59–66. https://doi.org/10.1007/s10103-014-1616-2 [DOI: 10.1007/s10103-014-1616-2]
  43. Obradović R, Kesić L, Mihailović D et al (2012) Low-level lasers as an adjunct in periodontal therapy in patients with diabetes mellitus. Diabetes Technol Ther 14:799–803. https://doi.org/10.1089/dia.2012.0027 [DOI: 10.1089/dia.2012.0027]

Grants

  1. 81870779/National Natural Science Foundation of China
  2. 2022-YF05-01760-SN/Chengdu Science and Technology Program

MeSH Term

Animals
Mice
Low-Level Light Therapy
Glucose Transporter Type 1
Diabetes Mellitus, Experimental
Inflammation
Interleukin-1beta
Periodontitis

Chemicals

Glucose Transporter Type 1
Interleukin-1beta
Journal Article

Word Cloud

Created with Highcharts 10.0.0periodontalLLLTdiabeticGLUT1/mTORpathwayage-relatedSASPlasertherapyinflammationmicechronicdiseasesenescencesecretoryphenotypepotentialperiodontitisLow-leveltissueexpressionfactorsobservedCOXtreatmentDiabetesmellitusDMrecentlyfoundsecondaryagingpatternregulatedassociatedpurposestudydetectefficacyspecificmechanismslow-levelhealingknowninflammagingDiabeticDPestablishedintraperitonealstreptozotocinSTZinjectionoralPgingivalisinoculationirradiation810 nm01 W398 mW/cm4 J/cm10 sappliedlocallyaroundlesionsevery3 days2consecutiveweeksMicro-CThematoxylin-eosinHEstainanalyzedsoftalveolarboneWesternblotsimmunohistochemistryimmunofluorescencestainingusedevaluateproteinchangesaging-relatedincludingtumornecrosisfactor-αinterleukinIL-1βIL-6reducedinhibitoryeffectdetectingrelatedmTORp-mTORGLUT1PKM2intracytoplasmicphotoreceptorkeycomponentanti-inflammatoryeffectssignificantincreasemacrophageslesionfindingssuggestmayregulatelow-grademodulatingsenescence-relatedtherebyofferingdiseasesalleviatesviaCytochromecoxidaseHyperglycemiaInflammatoryPeriodontalPhotobiomodulationSenescence-associated

Similar Articles

Cited By (1)