Abstract
Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions. During this process, endothelial cells (ECs), which are primarily responsible for angiogenesis, interact with the adjacent annulus fibrosus (AF) cells, which are the first line of defence against the invasion of vascular structures into deeper IVD regions. However, the accumulation of inflammatory and catabolic enzymes that results from this interaction promotes matrix degradation and an inflammatory response. Thus, regulating the production of these mediators and catabolic enzymes could ameliorate IVD degeneration. Photobiomodulation (PBM) therapy is a non-invasive stimulation known to have biologically beneficial effects on wound healing, tissue repair, and inflammation. Here, we examined the effects of PBM, administered at various wavelengths (645, 525, and 465 nm) and doses (16, 32, and 64 J/cm2), on EC-stimulated human AF cells. Our results show that PBM selectively inhibited the EC-mediated production of inflammatory mediators, catabolic enzymes, and neurotrophins by human AF cells in a dose- and wavelength-dependent manner. These results suggest that PBM could be a superior and advanced treatment strategy for IVD degeneration.
Highlights
Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions
AF cells exposed to ECCM (AFM), human annulus fibrosus (AF) cells cultured in EC-conditioned medium (ECCM); NC, negative control (Naïve AF cells)
We found that lactate dehydrogenase (LDH) release from ECCM-stimulated human AF cells was not significantly increased after PBM at any of the wavelengths tested (Fig. 6).Figure 7 shows a schematic diagram of the progressive IVD degeneration in vitro model based on the current study and the effects of PBM on human AF cells (Fig. 7 and Table 4)
Summary
Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions. During IVD degeneration, AF cells secrete inflammatory mediators, angiogenic activators, and ECM-modifying enzymes including interleukin (IL)-6, -8, vascular endothelial growth factor (VEGF), and MMPs1 These molecules promote matrix destruction and trigger an inflammatory response, resulting in the formation of a physical space and/or physiological response, which allows the ECs to invade deeper into the AF region. Our previous studies showed that PBM irradiation significantly reduces inflammatory mediators and ECM-modifying enzymes such as IL-6, IL-8, and MMPs in the presence of factors produced by activated THP-1 macrophages[12,13,14,15] These studies highlight the regulatory effects of inflammatory mediators during the early stages of IVD degeneration, which is thought to occur because of interactions between IVD and immune cells. We tested the effects of PBM on human AF cells exposed to conditioned media of ECs as novel therapies for regulating biological molecules
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