Estrogen receptor is involved in the osteoarthritis mediated by ATG16L1-NLRP3 activation
Fa-Xue Liao1,2*
, Shuo Yang1,2*, Zhi-Hong Liu1,2, Kai-Da Bo1,2, Peng-Fei Xu1,2, Jun Chang1,2
1Department of Orthopedics, the First Affiliated Hospital, Anhui Medical University, Hefei, China
2Anhui Public Health Clinical Center, Hefei, China
Keywords: ATG16L1, estrogen receptor, interleukin-1 beta, NLRP3, osteoarthritis.
Abstract
Objectives: This study aims to explore the mechanisms of dual regulation of osteoarthritis (OA) progression by the involvement of estrogen receptor (ER) in autophagy and inflammation.
Materials and methods: Bioinformatics methods were used to explore the relationship among associated genes. Western blot assays were used to detect related protein expression of OA in C28I2 and induced OA cellular model. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect OA related gene expression in C28I2 and induced OA cellular model. Co-immunoprecipitation (CO-IP) analysis were used to verify the direct interaction between ER and NOD-like receptor thermal protein domain associated protein 3 (NLRP3).
Results: The C28I2 cellular model of OA was induced by interleukin-1β (IL-1β). The small interfering ribonucleic acid (SiRNA)-mediated knockdown of autophagy-related 16 like 1 (ATG16L1) in C28I2 decreased the expression of MAP1LC3B (LC3B) and NLRP3. Besides, ER-beta (ERβ) agonist changed the gene expression of NLRP3 and ATG16L1. Moreover, CO-IP analysis indicated the direct interaction between ER and NLRP3.
Conclusion: Our study results revealed that ATG16L1, NLRP3, and IL-1β interacted closely and ERβ was involved in OA process by affecting autophagy and inflammatory activation.
* The two authors contributed equally to this study.
Citation: Liao FX, Yang S, Liu ZH, Bo KD, Xu PF, Chang J. Estrogen receptor is involved in the osteoarthritis mediated by Atg16L1- NLRP3 activation. Jt Dis Relat Surg 2024;35(3):513-520. doi: 10.52312/ jdrs.2024.1247.
This project was approved by the ethics committee of Anhui Public Health Clinical Center (North District of The First Affiliated Hospital of Anhui Medical University) in accordance with the principles of the Declaration of Helsinki and Guide for the Care and Use of Laboratory Ani-mals (date: 02.29.2024, no: PJ-YX2024-014). The study was conducted in accordance with the principles of the Declaration of Helsinki.
Writing-original draft, conceptualization, investigation, methodology, validation: F.X.L.; Investigation, methodology, formal analysis, resources, data curation: S.Y.; Software, formal analysis, visualization: Z.H.L.; Methodology, Investigation: K.D.B.; Formal analysis, validation, conceptualization: P.F.X.; Writing-review & editing, supervision, funding acquisition, conceptualization, project administration: J.C.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
This research was funded by the scientific research project of Anhui Province Health Commission (No. AHWJ2021b112), the research fund of Anhui Institute of Translational Medicine (NO. 2022zhyx-C91) and the scientific research fund of Anhui Medical University (No.2022xkj201) for supporting the research of this project.
We would like to thank the scientific research project of Anhui Province Health Commission (No.AHWJ2021b112), the research fund of Anhui Institute of Translational Medicine (NO. 2022zhyx-C91) and the scientific research fund of Anhui Medical University (No.2022xkj201) for supporting the research of this project.
The data that support the findings of this study are available from the corresponding author upon reasonable request.