The NLRP3/Caspase-1/Interleukin-1β Axis Is Active in Human Lumbar Cartilaginous Endplate Degeneration

Abstract

Background Modic changes are the MRI signal changes of degenerative lumbar vertebral endplate and which lead to or accelerate intervertebral disc degeneration. NLRP3, caspase-1, and interleukin-1b (IL-1b) play a pivotal role in the pathogenesis of many inflammatory diseases, such as osteoarthritis. However, the roles of IL-1b and its activators caspase-1 and NLRP3 are unclear in the degenerative endplate.Questions/purposes We asked: (1) What are the degenerative changes of the histologic features and chondrogenic markers' gene expressions between the cartilaginous endplates of patients with Modic changes and trauma (control)? (2) How does the NLRP3/caspase-1/IL-1b axis in the cartilaginous endplates of patients with Modic changes compare with control (trauma) specimens? Methods Surgical specimens of cartilaginous endplates were divided into Modic changes (n = 56) and the trauma control (n = 16) groups. Hematoxylin and eosin and safranin O staining of cartilaginous endplate tissues were done to evaluate the extracellular matrix. Reverse transcription-polymerase chain reaction was performed on these tissues to investigate mRNA expression of type II collagen (Col II), SOX-9, matrix metalloproteinase-3, and a disintegrin like and metalloproteinase thrombospondin type I motifs-5. NLRP3, caspase-1, and IL-1b were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Results Hematoxylin and eosin and safranin O staining showed the extracellular matrix degraded in the cartilaginous endplates of patients with Modic changes but not in the control cartilaginous endplates. Chondrogenic Col II (p = 0.024) and SOX9 (p = 0.053) were downregulated in the Modic changes group compared with the control group. In contrast to the control group, the transcriptional levels of

Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

“…Regarding the origin of IL-1β, Tang et al reported that the NLRP3/caspase-1/IL-1β axis is active in the CEP of patients with endplate degeneration and that IL-1β can be secreted by the CEP [18]. IL-1β was also detected in the culture medium of degenerating CEP cells [5], and IL-1β was produced by both IVD cells and immune cells [14, 16].…”

“…Numerous inflammatory factors and proteolytic enzymes are involved in IVD degeneration [6-8]. Interleukin (IL)-1β is one of the major cytokines that increases the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, and it plays a key role in the degeneration of the nucleus pulposus (NP) [9-17] and cartilaginous endplate (CEP) [18, 19]. The underlying molecular mechanism of IL-1β is mainly mediated by activating the NF-κB-dependent signalling pathway [8, 20] and the mitogen-activated protein kinase (MAPK) signalling pathway [21-25].…”

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

“…NOD‐like receptor protein 3 (NLRP3) inflammasomes are essential components of innate immune defense against type 2 diabetes, Alzheimer's disease, and atherosclerosis . Several lines of evidence suggested that excessive activation of the NLRP3 inflammasomes results in the production of downstream caspase‐1 and interleukin (IL)‐1β, which participate in the pathogenesis of IDD and were positively associated with the grades of disk degeneration . Further studies indicated that the activation of thioredoxin‐interacting protein (TXNIP)‐NLRP3 inflammasome signal pathway is closely related to the occurrence and development of IDD .…”

Bromodomain‐containing protein 4 inhibition alleviates matrix degradation by enhancing autophagy and suppressing NLRP3 inflammasome activity in NP cells

“…It is characterized by activation of caspase‐1/4/5/11, cleavage, and activation of the pore‐forming effector GSDMD and release of the pro‐inflammatory cytokines IL‐1β and IL‐18 (Kovacs & Miao, 2017; Liu & Lieberman, 2017). Previous studies have reported that the NLRP3/caspase‐1/IL‐1β axis is active in human cartilaginous endplate degeneration and associated with the grade of IDD (Chen et al, 2015; Tang et al, 2016). In addition, NLRP3 inflammasome‐mediated pyroptosis can be negatively regulated by honokiol and activated by advanced glycation end products in NP cells (Song et al, 2017; Tang et al, 2018).…”

“…The N‐terminal cleavage products then form membrane pores, causing cell lysis and release of the inflammatory factor IL‐1β, which is essential for immune responses (Aglietti & Dueber, 2017; Kovacs & Miao, 2017; Man & Kanneganti, 2015; Shi, Gao, & Shao, 2017; Upton & Chan, 2014). Importantly, it has been demonstrated that the NLRP3/caspase‐1/IL‐1β axis is associated with the grade of disc degeneration, and that the NLRP3 inflammasome is involved in IDD(Chen et al, 2015; Tang et al, 2016). However, the exact mechanism of NLRP3 inflammasome regulation in NP cells remains to be studied.…”