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Photobiomodulation with 630-nm LED radiation inhibits the proliferation of human synoviocyte MH7A cells possibly via TRPV4/PI3K/AKT/mTOR signaling pathway

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Abstract

Phototherapy has been used to treat postoperative pain and inflammatory response in rheumatoid arthritis. Confidence in this approach, however, is impaired by lack of understanding of the light-triggered cellular and molecular mechanisms. The purpose of this study was to characterize the response of human synoviocyte MH7A cells to visible LED red light in an attempt to elucidate the associated action mechanism. Human synoviocyte MH7A cells were treated with 630-nm LED light after stimulation of tumor necrosis factor-α (TNF-α). The effects of light radiation on cell proliferation and migration were detected by MTT assay and scratch test. The expressions of inflammatory cytokines were measured using RT-qPCR. This was followed by detection of the levels of extracellular proteins IL-6 and IL-8 after differential radiation. Furthermore, the expression levels and activation of proteins on PI3K/AKT/mTOR signaling pathway were examined with Western blot. In terms of the proliferation and migration, repeated radiation with LED red light (630 nm, 26 and 39 J/cm2) exerted an inhibitory effect on synoviocyte MH7A cells. Expression of inflammatory factors (IL-6, IL-1β, IL-8, and MMP-3) was reduced; meanwhile, the expression of anti-inflammatory factor IL-10 was promoted. At the protein level, treatment with 39 J/cm2 of LED red light could decrease the level of extracellular protein (IL-6 and IL-8) and affect the expression and phosphorylation of proteins on TRPV4/PI3K/AKT/mTOR signaling pathway induced by TNF-α. These results demonstrated that LED red light (630 nm) inhibits proliferation and migration of MH7A cells. The growth-inhibiting effects of LED red light on human synoviocyte MH7A cells appear to be associated with regulation of the TRPV4/PI3K/AKT/mTOR signaling pathway.

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References

  1. Alivernini S, Tolusso B, Fedele AL, Mario CD, Ferraccioli G, Gremese E (2019) The B side of rheumatoid arthritis pathogenesis. Pharmacol Res. https://doi.org/10.1016/j.phrs.2019.104465

  2. Bustamante MF, Garcia-Carbonell R, Whisenant KD et al (2017) Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 19(1):110

    Google Scholar 

  3. Hansch A, Frey O, Gajda M et al (2008) Photodynamic treatment as a novel approach in the therapy of arthritic joints. Lasers Surg Med 40(4):265–272

    Google Scholar 

  4. Neupane J, Ghimire S, Shakya S et al (2010) Effect of light emitting diodes in the photodynamic therapy of rheumatoid arthritis. Photodiagn Photodyn Ther 7(1):44–49

    Google Scholar 

  5. Alves AC, DE Carvalho PT, Parente M et al (2013) Low-level laser therapy in different stages of rheumatoid arthritis: a histological study. Lasers Med Sci 28(2):529–536

    Google Scholar 

  6. Meneses Calderon J, Gonzalez Sanchez I, Aburto Huacuz G et al (2015) Trends of inflammatory markers and cytokines after one month of phototherapy in patients with rheumatoid arthritis. Acta Med Acad 44(2):102–108

    Google Scholar 

  7. Lin L, Cheng K, Tan MT et al (2019) Comparison of the effects of 10.6-mum infrared laser and traditional moxibustion in the treatment of knee osteoarthritis. Lasers Med Sci. https://doi.org/10.1007/s10103-019-02863-9

  8. Yamaura M, Yao M, Yaroslavsky I et al (2009) Low level light effects on inflammatory cytokine production by rheumatoid arthritis synoviocytes. Lasers Surg Med 41(4):282–290

    Google Scholar 

  9. DE Freitas LF, Hamblin MR (2016) Proposed mechanisms of photobiomodulation or low-level light therapy. IEEE J Sel Top Quantum Electron 22(3):1–17

    Google Scholar 

  10. Hamblin MR (2017) Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 4(3):337–361

    CAS  Google Scholar 

  11. Pang XIAO-FENG (2012) The mechanism and properties of bio-photon emission and absorption in protein molecules in living systems. J Appl Phys 111(9):93519–93510

    Google Scholar 

  12. Zhou M, Fan ZX, Shao JD et al (2009) Thermal effects of optical film with the combined irradiation of different wavelength lasers. Acta Photonica Sin 38(10):2608–2612

    Google Scholar 

  13. Yang H (2005) Numerical simulation and experimental study on optothermal response of multilayer biological tissue under pulse laser irradiation. Proc SPIE 5630:711–722

    Google Scholar 

  14. Pang XF (2002) Thermally biological effects and its medical functions of the infrared rays absorbed by living systems. Int J Infrared Millimeter Waves 23(3):375–391

    CAS  Google Scholar 

  15. Fadhali MMA (2015) Analysis of photon transport in biological tissue and the subsequent heating effects. Int J Therm Sci 98:60–67

    Google Scholar 

  16. Mustafa FH, Jaafar MS (2012) Comparison of wavelength-dependent penetration depths of lasers in different types of skin in photodynamic therapy. Indian J Phys 87(3):203–209

    Google Scholar 

  17. Pinheiro AL, Soares LG, Cangussu MC et al (2012) Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins and guided bone regeneration: a Raman spectroscopic study. Lasers Med Sci 27(5):903–916

    Google Scholar 

  18. Brassolatti P, DE Andrade ALM, Bossini PS et al (2018) Photobiomodulation on critical bone defects of rat calvaria: a systematic review. Lasers Med Sci 33(9):1841–1848

    Google Scholar 

  19. Reedquist KA, Ludikhuize J, Tak PP (2006) Phosphoinositide 3-kinase signalling and FoxO transcription factors in rheumatoid arthritis. Biochem Soc Trans 34(Pt 5):727–730

    CAS  Google Scholar 

  20. Lefevre S, Meier FM, Neumann E et al (2015) Role of synovial fibroblasts in rheumatoid arthritis. Curr Pharm Des 21(2):130–141

    CAS  Google Scholar 

  21. Zhang Y, Song S, Fong CC et al (2003) cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated with red light. J Invest Dermatol 120(5):849–857

    CAS  Google Scholar 

  22. Hawkins D, Abrahamse H (2005) Biological effects of helium-neon laser irradiation on normal and wounded human skin fibroblasts. Photomed Laser Surg 23(3):251–259

    CAS  Google Scholar 

  23. Hawkins DH, Abrahamse H (2006) The role of laser fluence in cell viability, proliferation, and membrane integrity of wounded human skin fibroblasts following helium-neon laser irradiation. Lasers Surg Med 38(1):74–83

    Google Scholar 

  24. Mignon C, Uzunbajakava NE, Castellano-Pellicena I et al (2018) Differential response of human dermal fibroblast subpopulations to visible and near-infrared light: potential of photobiomodulation for addressing cutaneous conditions. Lasers Surg Med 50(8):859–882

    Google Scholar 

  25. Huang YY, Sharma SK, Carroll J et al (2011) Biphasic dose response in low level light therapy - an update. Dose-Response 9(4):602–618

    CAS  Google Scholar 

  26. Langella LG, Casalechi HL, Tomazoni SS et al (2018) Photobiomodulation therapy (PBMT) on acute pain and inflammation in patients who underwent total hip arthroplasty-a randomized, triple-blind, placebo-controlled clinical trial. Lasers Med Sci 33(9):1933–1940

    Google Scholar 

  27. Mitra A, Raychaudhuri SK, Raychaudhuri SP (2012) IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine 60(1):38–42

    CAS  Google Scholar 

  28. Garcia S, Liz M, Gomez-Reino JJ et al (2010) Akt activity protects rheumatoid synovial fibroblasts from Fas-induced apoptosis by inhibition of bid cleavage. Arthritis Res Ther 12(1):R33

    Google Scholar 

  29. Wu T, Mohan C (2009) The AKT axis as a therapeutic target in autoimmune diseases. Endocr Metab Immune Disord Drug Targets 9(2):145–150

    CAS  Google Scholar 

  30. Malemud CJ (2015) The PI3K/Akt/PTEN/mTOR pathway: a fruitful target for inducing cell death in rheumatoid arthritis? Future Med Chem 7(9):1137–1147

    CAS  Google Scholar 

  31. Li G, Liu Y, Meng F et al (2019) LncRNA MEG3 inhibits rheumatoid arthritis through miR-141 and inactivation of AKT/mTOR signalling pathway. J Cell Mol Med 23(10):7116–7120

    CAS  Google Scholar 

  32. Du H, Zhang X, Zeng Y et al (2019) A novel phytochemical, DIM, inhibits proliferation, migration, invasion and TNF-alpha induced inflammatory cytokine production of synovial fibroblasts from rheumatoid arthritis patients by targeting MAPK and AKT/mTOR signal pathway. Front Immunol 10:1620

    CAS  Google Scholar 

  33. Liu T C, Duan R, Yin P J et al (2000) Membrane mechanism of low-intensity laser biostimulation on a cell. 186–192

  34. Liu TC, Jiao JL, Xu XY et al (2005) Photobiomodulation: phenomenology and its mechanism. Proc SPIE 5630:185–191

    CAS  Google Scholar 

  35. Montell C (2005) The TRP superfamily of cation channels. Sci STKE Sig Transduct Knowl Environ 2005(272):re3

    Google Scholar 

  36. Yang WZ, Chen JY, Yu JT et al (2007) Effects of low power laser irradiation on intracellular calcium and histamine release in RBL-2H3 mast cells. Photochem Photobiol 83(4):979–984

    CAS  Google Scholar 

  37. Shibasaki K (2016) TRPV4 ion channel as important cell sensors. J Anesth 30(6):1014–1019

    Google Scholar 

  38. Takahashi N, Hamada-Nakahara S, Itoh Y et al (2014) TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P(2). Nat Commun 5:4994

    CAS  Google Scholar 

  39. Nam S, Gupta VK, Lee HP et al (2019) Cell cycle progression in confining microenvironments is regulated by a growth-responsive TRPV4-PI3K/Akt-p27(Kip1) signaling axis. Sci Adv 5(8):eaaw6171

    CAS  Google Scholar 

  40. Atobe M (2019) Activation of transient receptor potential vanilloid (TRPV) 4 as a therapeutic strategy in osteoarthritis. Curr Top Med Chem. https://doi.org/10.2174/1568026619666191010162850

  41. Denadai-Souza A, Martin L, DE Paula MA et al (2012) Role of transient receptor potential vanilloid 4 in rat joint inflammation. Arthritis Rheum 64(6):1848–1858

    CAS  Google Scholar 

  42. Mcnulty AL, Leddy HA, Liedtke W et al (2015) TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedeberg's Arch Pharmacol 388(4):437–450

    CAS  Google Scholar 

  43. Itoh Y, Hatano N, Hayashi H et al (2009) An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes. Am J Phys Cell Physiol 297(5):C1082–C1090

    CAS  Google Scholar 

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Acknowledgments

We thank Truwin Optoelectronic Medical (Beijing, China) for building the LED device according to our design.

Funding

This work was supported by the National Major Project for the research task (no. 2017YFB040380).

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Correspondence to Wuqi Song.

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Meng, C., Xia, Q., Wu, H. et al. Photobiomodulation with 630-nm LED radiation inhibits the proliferation of human synoviocyte MH7A cells possibly via TRPV4/PI3K/AKT/mTOR signaling pathway. Lasers Med Sci 35, 1927–1936 (2020). https://doi.org/10.1007/s10103-020-02977-5

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