The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration.

Chang Liu,Feng-Juan Lyu,Qiujian Zheng,Zhantao Deng,Jing Tan,Guoyan Liang,Zhenhan Deng

doi:10.1155/2021/2933199

Abstract

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1–5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

Highlights

Low back pain (LBP) imposes huge social and economic burdens [1, 2]
As a crucial mediator of pain and participant of inflammation signaling, cyclooxygenase 2 (COX2) may play an important role in intervertebral disc degeneration (IVDD) and LBP
Though we showed that IL-1β can regulate COX2 expression in the nucleus pulposus (NP), much detail is lacking to reveal the upstream and downstream signaling of COX2 in IVDD

Summary

Introduction

Low back pain (LBP) imposes huge social and economic burdens [1, 2]. It is estimated that about 80% of the world’s population suffer from low back pain at least once in their lifetime. In the United States, LBP is the fifth leading cause of patient visits and the third leading cause of surgery [3]. Imaging examination shows that patients with low back pain are often accompanied by intervertebral disc degeneration (IVDD) [5, 6]. The intervertebral disc (IVD) is the main joint connecting two adjacent vertebral bones in the spine. It is composed of three closely connected parts: nucleus pulposus (NP), annulus fibrous (AF), and cartilage endplate (EP). In the process of IVDD, the decrease in proteoglycan and collagen in the extracellular matrix (ECM) directly reduces the hydration capacity of IVD, leading to the decrease in water content in NP, which in turn leads to intervertebral disc

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