Photobiomodulation on human annulus fibrosus cells during the intervertebral disk degeneration: extracellular matrix-modifying enzymes

Abstract

Destruction of extracellular matrix (ECM) leads to degeneration of the intervertebral disk (IVD), which is a major contributor to many spine disorders. IVD degeneration is induced by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), which are secreted by immune cells, including macrophages and neutrophils. The cytokines modulate ECM-modifying enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human annulus fibrosus (AF) cells. The resulting imbalance in catabolic and anabolic enzymes can cause generalized back, neck, and low back pain (LBP). Photobiomodulation (PBM) is known to regulate inflammatory responses and wound healing. The aim of this study was to mimic the degenerative IVD microenvironment, and to investigate the effect of a variety of PBM conditions (wavelength: 635, 525, and 470 nm; energy density: 16, 32, and 64 J/cm 2 ) on the production of ECMmodifying-enzymes by AF cells under degenerative conditions induced by macrophage-conditioned medium (MCM), which contains pro-inflammatory cytokines such as TNF-α and IL-β secreted by macrophage during the development of intervertebral disk inflammation. We showed that the MCMstimulated AF cells express imbalanced ratios of TIMPs (TIMP-1 and TIMP-2) and MMPs (MMP-1 and MMP-3). PBM selectively modulated the production of ECMmodifying enzymes in AF cells. These results suggest that PBM can be a therapeutic tool for degenerative IVD disorders.

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

“…As for the ECM, studies have found that immunocytes could interfere with IVD ECM remodeling and downregulate aggrecan and collagen II expression [48]. In addition, the expression of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) were increased in IVD with autoimmune reaction, causing the degradation of ECM [51,52]. Taken together, the auto-immune reaction could stimulate immunocytes and inflammatory cytokines infiltration, and these factors could in turn impact on the IVD with harmful influence.…”

lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis

“…In contrast, genetic heredity is the predominant risk factor for degenerative disc disease and is estimated to cause over 70% of cases . Although the pathogenesis of IDD is not completely understood, it is well established that progressive loss of ECM, cell proliferation, inflammatory response, angiogenesis, apoptosis, autophagy, and oxidative stress play critical roles in the occurrence and development of disc degeneration …”

“…40,41 Although the pathogenesis of IDD is not completely understood, it is well established that progressive loss of ECM, cell proliferation, inflammatory response, angiogenesis, apoptosis, autophagy, and oxidative stress play critical roles in the occurrence and development of disc degeneration. [42][43][44][45][46][47] Like the well-known short non-coding RNAs such as miRNAs, 1 49 Overexpression of FAF1 is known to potentiate Fas-mediated apoptosis and suppress the degradation of ubiquitinated proteins, leading to a significant increase of cell death. 50,51 These authors also found that in addition to upregulation of the nearby enhancer-like lncRNA, RP11-296A18.3, FAF1 is significantly increased in degenerative discs compared with the normal discs.…”

Reactive Oxygen Species‐Scavenging Scaffold with Rapamycin for Treatment of Intervertebral Disk Degeneration

“…Intervertebral disk degeneration (IVDD), a natural progression of aging, is one of the commonest clinical disease with manifestations including pain of low back . The incidence rate for IVDD in adults is more than 30% globally .…”

“…IVD gradually degenerates due to many factors, such as the immune balance of the microenvironment disturbs. Recent studies indicate that increased chronic inflammatory response is closely connected with the processes of the IVDD . Chronic inflammatory microenvironment consists of various activated inflammatory cells, pro‐inflammatory mediators, high levels of reactive oxygen species (ROS), and so on .…”