Skip to main content
Springer Nature Link
Log in

Low-level laser irradiation stimulates tenocyte proliferation in association with increased NO synthesis and upregulation of PCNA and cyclins

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Low-level laser therapy is commonly used to treat tendinopathy or tendon injury. Tendon healing requires tenocyte migration to the repair site, followed by proliferation and synthesis of the extracellular matrix. There are few evidence to elucidate that low-level laser promote tenocyte proliferation. This study was designed to determine the effect of laser on tenocyte proliferation. Furthermore, the association of this effect with secretion of nitric oxide (NO) and the expressions of proliferating cell nuclear antigen (PCNA) and cyclins D1, E, A, and B1 was investigated. Tenocytes intrinsic to rat Achilles tendon were treated with low-level laser (660 nm). Tenocyte proliferation was evaluated by MTT assay and immunocytochemistry with Ki-67 stain. NO in the conditioned medium was measured by ELISA. Western blot analysis was used to evaluate the protein expressions of PCNA and cyclins D1, E, A, and B1. The results revealed that tenocytes proliferation was enhanced dose dependently by laser. NO secretion was increased after laser treatment. PCNA and cyclins E, A, and B1 were upregulated by laser. In conclusion, low-level laser irradiation stimulates tenocyte proliferation in a process that is mediated by upregulation of NO, PCNA, and cyclins E, A, and B1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Goldman JA (1981) Investigative studies of laser technology in rheumatology and immunology. In: Goldman L (ed) The biomedical laser: technology and clinical applications. Springer-Verlag, New York, p 293

    Chapter  Google Scholar 

  2. Basford JR, Baxter GD (2010) Therapeutic physical agents. In: Frontera WR (ed) DeLisa’s physical medicine and rehabilitation, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1706–1707

    Google Scholar 

  3. Tumilty S, Munn J, McDonough S, Hurley DA, Basford JR, Baxter GD (2010) Low level laser treatment of tendinopathy: a systematic review with meta-analysis. Photomed Laser Surg 28:3–16

    Article  PubMed  Google Scholar 

  4. Bjordal JM, Lopes-Martins RA, Joensen J, Couppe C, Ljunggren AE, Stergioulas A, Johnson MI (2008) A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendinopathy (tennis elbow). BMC Musculoskelet Disord 9:75

    Article  PubMed Central  PubMed  Google Scholar 

  5. Stergioulas A, Stergioula M, Aarskog R, Lopes-Martins RA, Bjordal JM (2008) Effects of low-level laser therapy and eccentric exercises in the treatment of recreational athletes with chronic achilles tendinopathy. Am J Sports Med 36:881–887

    Article  PubMed  Google Scholar 

  6. Saunders L (2003) Laser versus ultrasound in the treatment of supraspinatus tendinosis: randomised controlled trial. Physiotherapy 89:365–373

    Article  Google Scholar 

  7. Casalechi HL, Nicolau RA, Casalechi VL, Silveira L Jr, De Paula AM, Pacheco MT (2009) The effects of low-level light emitting diode on the repair process of Achilles tendon therapy in rats. Lasers Med Sci 24:659–665

    Article  PubMed  Google Scholar 

  8. Oliveira FS, Pinfildi CE, Parizoto NA, Liebano RE, Bossini PS, Garcia EB, Ferreira LM (2009) Effect of low level laser therapy (830 nm) with different therapy regimes on the process of tissue repair in partial lesion calcaneous tendon. Lasers Surg Med 41:271–276

    Article  PubMed  Google Scholar 

  9. Fillipin LI, Mauriz JL, Vedovelli K, Moreira AJ, Zettler CG, Lech O, Marroni NP, Gonzalez-Gallego J (2005) Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon. Lasers Surg Med 37:293–300

    Article  PubMed  Google Scholar 

  10. Nouruzian M, Alidoust M, Bayat M, Bayat M, Akbari M (2013) Effect of low-level laser therapy on healing of tenotomized Achilles tendon in streptozotocin-induced diabetic rats. Lasers Med Sci 28:399–405

    Article  PubMed  Google Scholar 

  11. Guerra Fda R, Vieira CP, Almeida MS, Oliveira LP, de Aro AA, Pimentel ER (2013) LLLT improves tendon healing through increase of MMP activity and collagen synthesis. Lasers Med Sci 28:1281–1288

    Article  PubMed  Google Scholar 

  12. Karu T (1999) Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B 49:1–17

    Article  CAS  PubMed  Google Scholar 

  13. Lane N (2006) Cell biology: power games. Nature 443:901–903

    Article  CAS  PubMed  Google Scholar 

  14. Tafur J, Mills PJ (2008) Low-intensity light therapy: exploring the role of redox mechanisms. Photomed Laser Surg 26:323–328

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Chen CH, Tsai JL, Wang YH, Lee CL, Chen JK, Huang MH (2009) Low-level laser irradiation promotes cell proliferation and mRNA expression of type I collagen and decorin in porcine Achilles tendon fibroblasts in vitro. J Orthop Res 27:646–650

    Article  CAS  PubMed  Google Scholar 

  16. Alexandratou E, Yova D, Handris P, Kletsas D, Loukas S (2002) Human fibroblast alterations induced by low power laser irradiation at the single cell level using confocal microscopy. Photochem Photobiol Sci 1:547–552

    Article  CAS  PubMed  Google Scholar 

  17. Lubart R, Breitbart H (2000) Biostimulative effects of low-energy lasers and their implications for medicine. Drug Dev Res 50:471–475

    Article  CAS  Google Scholar 

  18. Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677

    Article  CAS  PubMed  Google Scholar 

  19. Pines J (1994) Protein kinases and cell cycle control. Semin Cell Biol 5:399–408

    Article  CAS  PubMed  Google Scholar 

  20. Prelich G, Stillman B (1988) Coordinated leading and lagging strand synthesis during SV40 DNA replication in vitro requires PCNA. Cell 53:117–126

    Article  CAS  PubMed  Google Scholar 

  21. Morris GF, Mathews MB (1989) Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem 264:13856–13864

    CAS  PubMed  Google Scholar 

  22. Sachs F (1991) Mechanical transduction by membrane ion channels: a mini review. Mol Cell Biochem 104:57–60

    Article  CAS  PubMed  Google Scholar 

  23. Tsai WC, Hsu CC, Tang FT, Chou SW, Chen YJ, Pang JH (2005) Ultrasound stimulation of tendon cell proliferation and upregulation of proliferating cell nuclear antigen. J Orthop Res 23:970–976

    Article  CAS  PubMed  Google Scholar 

  24. O’Brien M (1992) Functional anatomy and physiology of tendons. Clin Sports Med 11:505–520

    PubMed  Google Scholar 

  25. Leadbetter WB (1992) Cell-matrix response in tendon injury. Clin Sports Med 11:533–578

    CAS  PubMed  Google Scholar 

  26. Murrell GA, Szabo C, Hannafin JA, Jang D, Dolan MM, Deng XH, Murrell DF, Warren RF (1997) Modulation of tendon healing by nitric oxide. Inflamm Res 46:19–27

    Article  CAS  PubMed  Google Scholar 

  27. Bokhari AR, Murrell GA (2012) The role of nitric oxide in tendon healing. J Shoulder Elbow Surg 21:238–244

    Article  PubMed  Google Scholar 

  28. Nichols SP, Storm WL, Koh A, Schoenfisch MH (2012) Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues. Adv Drug Deliv Rev 64:1177–1188

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR (2010) Role of low-level laser therapy in neurorehabilitation. Phys Med Rehabil 2:S292–S305

    Google Scholar 

  30. Girard F, Strausfeld U, Fernandez A, Lamb NJ (1991) Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67:1169–1179

    Article  CAS  PubMed  Google Scholar 

  31. Minshull J, Pines J, Golsteyn R, Standart N, Mackie S, Colman A, Blow J, Ruderman JV, Wu M, Hunt T (1989) The role of cyclin synthesis, modification and destruction in the control of cell division. J Cell Sci Suppl 12:77–97

    Article  CAS  PubMed  Google Scholar 

  32. Xiong Y, Zhang H, Beach D (1992) D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell 71:505–514

    Article  CAS  PubMed  Google Scholar 

  33. Bjordal JM, Couppe C, Ljunggren AE (2001) Low level laser therapy for tendinopathy: evidence of a dose response. Phys Ther Rev 6:91–99

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank the National Science of Council, Taiwan, for the financial support of this research (grant no. 99-2314-B-182A-108).

Author information

Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Gueishan Township, Taoyuan County, Taiwan

    Wen-Chung Tsai, Ju-Wen Cheng, Jean-Lon Chen, Chen-Yin Chen, Yu-Hsin Liao & Miao-Sui Lin

  2. College of Medicine, Chang Gung University, Gueishan Township, Taoyuan County, Taiwan

    Wen-Chung Tsai & Jean-Lon Chen

  3. Department of Physical Medicine and Rehabilitation, Taiwan Landseed Hospital, Ping-jen City, Taoyuan County, Taiwan

    Hsiang-Ning Chang

  4. Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259, Wen-Hwa 1st Road, Gueishan Township, Taoyuan County, 333, Taiwan

    Jong-Hwei S. Pang

Authors
  1. Wen-Chung Tsai
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Ju-Wen Cheng
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Jean-Lon Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Chen-Yin Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Hsiang-Ning Chang
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Yu-Hsin Liao
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Miao-Sui Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Jong-Hwei S. Pang
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Jong-Hwei S. Pang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsai, WC., Cheng, JW., Chen, JL. et al. Low-level laser irradiation stimulates tenocyte proliferation in association with increased NO synthesis and upregulation of PCNA and cyclins. Lasers Med Sci 29, 1377–1384 (2014). https://doi.org/10.1007/s10103-014-1528-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10103-014-1528-1

Keywords