Possible involvement of the oxLDL/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation

Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.

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“…, as well as scavenger receptors (SRs) ( 57 ). Similar sets of PRRs have been reported to modulate bone metabolism ( 58 – 61 ).…”

Section: Cells Of the Myeloid Lineagesupporting

confidence: 72%

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

2021

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“…Thirdly, the oxidized low-density lipoprotein (oxLDL) and the increased expression of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) that are caused by dyslipidaemia may also be involved in the development of symptomatic IDH. Our previous study suggested [44] that the levels of the oxLDL and LOX-1 were positively correlated with the extent of IDH. The mechanism of action involved the increase in the expression of MMP3 that was induced by LOX-1.…”

Section: Discussionmentioning

confidence: 92%

Serum Apolipoprotein B/apolipoprotein A1 Ratio in Relation to Intervertebral Disc Herniation : A Cross-sectional Frequency-Matched Case-Control Study

Chen

Guo

et al. 2020

Preprint

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BackgroundIn recent decades, the serum lipid profile of apolipoprotein(a) (Lp(a)) level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/ApoA1) ratio were found more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the serum lipid levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were found associated with symptomatic IDH, no studies have been conducted to date for the evaluation of the association of Apo AI, Apo B, Lp(a) and Apo B/Apo AI levels with symptomatic IDH.MaterialsA total of 1,839 Chinese patients were recruited in the present study. 918 patients were diagnosed as IDH cases and were enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B and Apo B/Apo AI were examined and analyzed.ResultsThe patients in the control group were collected randomly from patients who were matched with the baseline levels of the aforementioned lipid molecular. The patients with IDH exhibited significantly higher TC, TG, LDL, Apo B and Lp(a) levels compared with the control subjects. The percentage of high-TC, high-TG, high-LDL, high-Apo B and high-Lp(a) were significantly higher in the IDH group. However, hyperlipidaemia was not associated with the degenerated segment of the IDH (P=0.201). The odds ratios (OR) for the incidence of IDH with an elevated LDL-C, TC, TG, Lp(a), Apo B and Apo B/Apo AI were 1.583, 1.74, 1.62, 1.58, 1.49 and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a) and incidence of IDH was significant (R2LDL=0.017; R2TC=0.004; R2TG=0.015; R2Apo B=0.004; R2LP(a)=0.021) (P<0.05). ConclusionsThe present study suggests that elevated levels of serum TC, TG, LDL, Apo B, Lp(a) and Apo B/Apo AI are associated with a higher risk for IDH.

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“…oxLDL has been detected in human IVD tissues, and compared with normal disc tissues, the proportion of oxLDL was significantly higher in degenerated discs. More importantly, the mean percentage of oxLDL‐positive‐immunostained cells in the AF was higher than that in the NP 17 . The AF seems, therefore, to be more susceptible to oxLDL.…”

Section: Introductionmentioning

confidence: 84%

Drp1‐mediated mitochondrial fission is involved in oxidized low‐density lipoprotein‐induced AF cella poptosis

Jing

Huang

et al. 2020

Journal Orthopaedic Research

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This study aimed to assess the negative effect of oxidized low‐density lipoprotein (oxLDL) on annulus fibrosus (AF) cells and decipher the mechanism of action of the process. After treating AF cells with various concentrations (0, 25, 50, 100, and 200 μg/mL) of oxLDL for 24 and 48 hours, their viability was evaluated using cell counting kit‐8 and live/dead staining. The percentage of AF cell death was determined with Annexin V/propidium iodide apoptosis staining. The expression of proteins related to the mitochondrial apoptosis pathway was determined using Western blot. Additionally, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were assessed with JC‐1 staining and dichlorodihydrofluorescein diacetate ormitoSOX probes, respectively. Mitochondrial morphology was observed with a transmission electron microscope. After treatment with oxLDL, AF cell viability decreased, pro‐apoptosis proteins (such as Bax, cleaved caspase‐9, and cleaved caspase‐3) increased, and anti‐apoptosis proteins (Bcl‐2) declined. Excessive ROS and diminished MMP were also detected during this process, as were enhanced mitochondrial fission and augmented Drp1 expression. Furthermore, knocking down the expression of Drp1 rescued oxLDL‐induced AF cell death. Collectively, these results suggest that oxLDL induces AF cell death through a mitochondria‐related pathway. Enhanced mitochondrial fission was involved in oxLDL‐induced AF cell death. Targeting Drp1, a target for regulating the process of mitochondrial fission, may be a feasible strategy for preventing intervertebral disc degeneration in hyperlipidemia.

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Possible involvement of the oxLDL/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation

Cited by 22 publications

References 49 publications

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

Immunoporosis: Role of Innate Immune Cells in Osteoporosis

Serum Apolipoprotein B/apolipoprotein A1 Ratio in Relation to Intervertebral Disc Herniation : A Cross-sectional Frequency-Matched Case-Control Study

Drp1‐mediated mitochondrial fission is involved in oxidized low‐density lipoprotein‐induced AF cella poptosis

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