Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration

Abstract

Intervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.

In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration

“…The IL-1β-mediated NF-κB (p65 and p50 subunits) signal transduction pathway is well known to control the expression of a number of inflammatory and catabolic genes 2 . In our previous study and the current study, IL-1β stimulation induced the translocation of p65 protein into the nucleus, resulting in the upregulation of IL-6, IL-8, MMP-1, and MMP-3 in human AF or NP cells [25][26][27] . IVD cells from degenerative conditions secreted and expressed VEGF under various experimental conditions 13,28,29 .…”

Current Knowledge and Future Therapeutic Prospects in Symptomatic Intervertebral Disc Degeneration

“…Kim, et al 34 investigated non-invasive direct stimulation to IVD cells using biphasic electrical currents or photobiomodulation and produced promising results, showing significantly suppressed expression of inflammatory mediators. 103 Although these trials are attractive, considering the non-invasive nature of energy transmission to IVDs, there remain some obstacles to obtaining a safe and effective method for delivering stimulus to the IVD, which lies in the center of the vertebral axis. As our knowledge of IVD biology and degeneration increases, more therapeutic candidates will become available.…”

Microfluidic Electroceuticals Platform for Therapeutic Strategies of Intervertebral Disc Degeneration: Effects of Electrical Stimulation on Human Nucleus Pulposus Cells under Inflammatory Conditions

“…Multiple lines of evidence have shown that immune cells, including monocytes, neutrophils, macrophages, and T cells, infiltrate the NP regions through these newly formed vascular structures [ 4 , 7 , 8 ]. Furthermore, marked increases in the expression of various factors associated with degeneration secreted by immune cells or NP cells, including IL-6, IL-8, and MMPs, have been noted in IVD [ 3 , 4 , 9 , 10 ]. Thus, an enhanced understanding of the interaction between IVD cells and immune cells could lead to the identification of novel therapeutic targets and establishment of treatment strategies for IVD disease.…”