An in vivo and in vitro study of the correlation between Paraoxonase 1 (PON1) and intervertebral disc degeneration (IVDD).
The aim of this study is to clarify the expression and role of PON1 on the process of IVDD.
IVDD is responsible for most of the spinal degenerative diseases. Inflammation and oxidative stress can deteriorate the living environment of nucleus pulposus (NP) cells, leading to IVDD. PON1 is an enzyme reported to have anti-inflammatory and anti-oxidative effects. There is no study about the correlation of PON1 expression with IVDD.
Immunohistochemical (IHC), hematoxylin and eosin (H&E) staining, and Western blot examined the expression of PON1 in 88 human disc samples (male: female 43: 45) and rat models (n = 5 each group). The level of PON1 is measured in the tumor necrosis factor (TNF)-α and oxidative stress (H2O2)-induced degenerative NP cell models using Western blot and reverse transcription-polymerase chain reaction (RT-qPCR). The TNF-α, interleukin (IL)-1β, Mito superoxide (SOX), aggrecan, and collagen II are detected in nucleus pulposus (NP) cells transfected with si-RNA of PON1 using Enzyme-Linked Immunosorbent Assay (ELISA), mitoSOX staining Western blot, and RT-qPCR.
The expression of PON1 is significantly suppressed in human and rat degenerative intervertebral discs. The level of PON1 is significantly decreased in TNF-α and oxidative stress (H2O2)-induced degenerative NP cell models. ELISA results show that the level of TNF-α and IL-1β obviously increased; Mito SOX staining indicates that the Mito SOX fluorescence significantly increased, and the expression of aggrecan and collagen reduced in NP cells transfected with si-RNA of PON1.
Our study indicates that low PON1 expression is predictive of severe IVDD; PON1 plays an important role of keeping the homeostatic balance of intervertebral discs, and therapeutic approach regarding PON1 may be helpful to alleviate IVDD in the future.
Level of Evidence: N/A
Paraoxonase 1 (PON1) is an enzyme with anti-inflammatory and anti-oxidative effects. Expression of PON1 is suppressed in degenerated discs and degenerative nucleus pulposus (NP) cell models. Knockdown of PON1 showed increased inflammatory and oxidative stress levels and decreased extracellular matrix levels in NP cells. PON1 might be a target for intervertebral disc degeneration treatment.
∗Department of Spine Surgery, the First Affiliated Hospital and Orthopedic Research Institute of Sun Yat-sen University, Guangzhou, China
†Department of Pain Research Center, Zhongshan Medical School, Sun Yat-Sen University, Guangdong, China
‡Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Address correspondence and reprint requests to Jianru Wang, PhD, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China; E-mail: email@example.com; Zhaomin Zheng, PhD, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, China; E-mail: firstname.lastname@example.org
Received 9 November, 2018
Revised 17 February, 2019
Accepted 14 March, 2019
F.C. and H.L. authors have contributed equally to this work.
The manuscript submitted does not contain information about medical device(s)/drug(s).
The Natural Science Foundation of Guangdong Province (Grant No: 2017A030313670), National Natural Science Foundation of China (81702178) and the Outstanding Young Investigator Support Program of The First Affiliated Hospital, Sun Yat-sen University (Y50156) funds were received in support of this work.
No relevant financial activities outside the submitted work.