Photodynamic activation as a molecular switch to promote osteoblast cell differentiation via AP-1 activation

Abstract

In photodynamic therapy (PDT), cells are impregnated with a photosensitizing agent that is activated by light irradiation, thereby photochemically generating reactive oxygen species (ROS). The amounts of ROS produced depends on the PDT dose and the nature of the photosensitizer. Although high levels of ROS are cytotoxic, at physiological levels they play a key role as second messengers in cellular signaling pathways, pluripotency, and differentiation of stem cells. To investigate further the use of photochemically triggered manipulation of such pathways, we exposed mouse osteoblast precursor cells and rat primary mesenchymal stromal cells to low-dose PDT. Our results demonstrate that low-dose PDT can promote osteoblast differentiation via the activation of activator protein-1 (AP-1). Although PDT has been used primarily as an anti-cancer therapy, the use of light as a photochemical “molecular switch” to promote differentiation should expand the utility of this method in basic research and clinical applications.

Chlorin e6 Functionalized Theranostic Multistage Nanovectors Transported by Stem Cells for Effective Photodynamic Therapy

“…In addition to triggering cell death, the versatility of the MSV platform could be used in combination with MSC to yield beneficial outcomes to provide aid for tissue regeneration applications. 48 …”

Photodynamic N-TiO2 Nanoparticle Treatment Induces Controlled ROS-mediated Autophagy and Terminal Differentiation of Leukemia Cells

“…6 ), strongly suggesting that oxidative stress and ROS formation are the main trigger for the cellular changes induced by photo-activated N-TiO 2 . PDT-mediated ROS strategies have been used in cancer therapy 6 7 8 27 , with the type and quantity of ROS members produced by PDT being dependent on the light dose and concentrations of the photosensitizer used 7 8 27 . In addition, PDT conditions have been shown to have an impact on changing cell fates and osteoblast differentiation 7 .…”

“…Under ultraviolet (UV)-light illumination, the valence band electrons of TiO 2 are excited to the conduction band and the resulting electron holes have the capability of generating various cellular reactive oxygen species (ROS), including hydroxyl radical (OH·), hydrogen peroxide (H 2 O 2 ), and superoxide (O2 − ) 4 5 . Irradiation-induced generation of ROS by a photosensitizer is called photodynamic therapy (PDT) and has been clinically approved for several diseases, including cancers 6 7 . The advantages of PDT compared to other anti-cancer strategies include the lack of known drug resistance and the ability to control ROS production in cancer cells by controlling PDT doses 6 7 8 .…”

“…Irradiation-induced generation of ROS by a photosensitizer is called photodynamic therapy (PDT) and has been clinically approved for several diseases, including cancers 6 7 . The advantages of PDT compared to other anti-cancer strategies include the lack of known drug resistance and the ability to control ROS production in cancer cells by controlling PDT doses 6 7 8 . The successful use of TiO 2 NPs in PDT has been reported for many different types of cancers, such as human cervical adenocarcinoma, hepatocarcinoma, non-small cell lung cancer, and leukemia 5 9 10 11 12 .…”

Biological Function of Low Reactive Level Laser Therapy (LLLT)

“…Furthermore, my colleagues and we also discovered changes in the functions of cells irradiated with lasers in the presence of low doses of PPIX [67]. As the intracellular photoacceptors, porphyrins mediate a wide variety of biochemical reactions through the production of reactive oxygen species following photoreception.…”