Mechanisms of tendon healing and matrix metabolism induced by low-level laser therapy

• Main Authors: Yun-Chien Huang, 黃韻倩
• Other Authors: Ming-Hong Chen
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/36485512865093873588

碩士 === 國立陽明大學 === 醫學工程研究所 === 99 === Low level laser therapy (LLLT) has been a widely used and well-accepted physical therapy modality for the management of tendon disorders. The physiological effects attributed to LLLT include pain reduction, accelerated tissue healing and reduction of inflammation. Although several authors have demonstrated the potential of LLLT in the facilitation of the tendon healing process, the molecular and biochemical mechanisms on tenocytes remain to be determined. Tenocytes are specialized, fibroblast-like cells of mesenchymal origin that constitute about 90% to 95% of the cellular elements of tendons and they play an important role in producing and maintaining extracellular matrix and initiating regenerative responses following injury or degeneration. Matrix metabolism is important for the maintenance and repair of tendons. It is regulated by some promoting and the compromising factors, such as inflammatory cytokines, growth factors and nitric oxide. The failure to properly regulate these factors may lead to improper matrix metabolism and play a role in the development of pathological tendon conditions. The therapeutic effect of LLLT could be explained by photostimulation of target tissue and cells. However, how tenocytes sense photonic energy and convert them into cascades of cellular and molecular events that ultimately lead to tendon adaptive physiological changes is not well understood. Many theories exist as to the mechanism of action for LLLT but simply put, photonic energy is absorbed by photon acceptor sites on the cell membrane which increases ATP production and membrane perturbation to lead to permeability changes, which will trigger secondary messengers, Ca2+ and NO, to initiate a cascade of intracellular signals. Mitogen-activated protein (MAP) kinases are serine/threonine-specific protein kinases that respond to extracellular stimuli and regulate various cellular activities. MAPK is crucial for the conversion of various stresses to tissue adaptation inducing signaling from the cytosol to the nucleus. More research is needed to determine the exact mechanism whereby photonic energy can stimulate tenocytes to restore homeostasis and stimulate tenocyte functions such as proliferation and protein syntheses through certain signal transduction pathways. The study aims to elucidate the effects of LLLT on cultured tenocytes, and to further investigate the biochemical mechanisms and MAPK signaling pathways of LLLT promoting tenocyte proliferation and regulating extracellular matrix metabolisms. Ga-As laser at 904nm was used to stimulate tenocyte of SD rat. The MTT assay was used to evaluate the mitochondria activity of the tenocytes after low-level laser. Adenosine triphosphate (ATP), nitric oxide (NO) and intracellular calcium concentration were determined following LLLT. Synthesis of collagen and transforming growth factor-β1 (TGF-β1) were determined and their gene expression was also studied. Low-level laser stimulate tenocyte proliferation and collagen synthesis with an optimal dose of 1J/cm2. The associated tenocyte proliferation is mediated by early up-regulation of PCNA. The mechanisms by which collagen synthesis both in protein and mRNA level is likely mediated by intracellular calcium release and upregulation of TGF-β1 through MAPK/ERK pathway. The molecular and cellular mechanisms of LLLT suggest that photons are absorbed by the mitochondria; they stimulate more ATP production and high levels of intracellular calcium, which then activates ERK pathway to induce TGF-β1 production and many gene transcript products responsible for the beneficial effects of LLLT.