Low-energy laser irradiation promotes synovial fibroblast proliferation by modulating p15 subcellular localization

Lasers Surg Med. 2009 Mar;41(3):232-9. doi: 10.1002/lsm.20750.


Background and objective: Low-energy laser irradiation (low-level laser therapy) (LELI/LLLT/photobiomodulation) has been found to modulate various biological effects, especially those involved in promoting cell proliferation. Synovial fibroblasts are important in maintaining the homeostasis of articular joints and have strong chondrogenetic capacity. Here, we investigated the effect and molecular basis of LELI on synovial fibroblast proliferation.

Study design/materials and methods: HIG-82 rabbit synovial fibroblasts were cultured, and laser irradiation (660 nm) was applied at the power density of 40 mW/cm(2) for 2 minutes, corresponding to laser fluence of 4.8 J/cm(2). The effect of LELI on cell proliferation, cell cycle progression, and expression of cyclin-dependent kinase inhibitors (CKIs) were investigated. We also examined whether the effects of LELI on HIG-82 cell proliferation were affected by cAMP content, which is known to influence the cell cycle via inducing CKIs.

Results: LELI promoted HIG-82 synovial fibroblast proliferation and induced cytoplasmic localization of cyclin-dependent kinase inhibitor p15 (INK4B/CDKN2B). Moreover, the proliferation of HIG-82 synovial fibroblasts was reduced by cAMP, while cAMP inhibitor, SQ22536, induced p15 cytoplasmic localization and as a result, elevated synovial fibroblast proliferation was observed. In addition, the promotive effect of LELI-induced HIG-82 synovial fibroblast proliferation was abolished by cAMP treatment. Our findings suggest that cAMP may be involved in the effect of LELI on synovial fibroblast proliferation.

Conclusion: We revealed the effect and molecular link involved in synovial fibroblast proliferation induced by 660-nm LELI. Our study provides new insights into the mechanisms by which LELI has biological effects on synovial fibroblast proliferation. These insights may contribute to further investigation on biological effects and application of LELI in regenerative medicine.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Cycle / radiation effects*
  • Cell Proliferation / radiation effects
  • Cells, Cultured
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / metabolism
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects*
  • Fluorescent Antibody Technique
  • Low-Level Light Therapy*
  • Rabbits
  • Synovial Membrane / cytology
  • Synovial Membrane / metabolism
  • Synovial Membrane / radiation effects*


  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclic AMP
  • Bromodeoxyuridine