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. 2024 Jul 8;35(3):513-520.
doi: 10.52312/jdrs.2024.1247. Epub 2024 Jul 8.

Estrogen receptor is involved in the osteoarthritis mediated by Atg16L1-NLRP3 activation

Fa-Xue Liao, Shuo Yang, Zhi-Hong Liu, Kai-Da Bo, Peng-Fei Xu, Jun Chang  1
Affiliations

Estrogen receptor is involved in the osteoarthritis mediated by Atg16L1-NLRP3 activation

Fa-Xue Liao et al. Jt Dis Relat Surg. .

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.

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Conflict of interest statement

Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1
Figure 1. Analysis of the relationship between Atgl6L1 and NLRP3 using bioinformatics software.
Atg16L1: Autophagy-related 16 like 1; NLRP3: NOD-like receptor thermal protein domain associated protein.
Figure 2
Figure 2. The expression of autophagy and inflammatory related proteins before and after ER intervention. NLRP3, MMP1, TNF-α, AtgI6L1, LC3B, ER-α and ER-β were involved in western blot analysis.
ER: Estrogen receptor; NLRP3: NOD-like receptor thermal protein domain associated protein; MMP1: Matrix metalloproteinase 1; TNF-α: Tumor necrosis factor alpha; AtgI6L1: Autophagy-related 16 like 1; LC3B: Light chain 3 beta; ER-α: Estrogen receptor-alpha; ER-β:Estrogen receptor-beta.
Figure 3
Figure 3. The expression of autophagy and inflammatory related proteins before and after Atg16L1 protein silencing treatment. (a) LC3B, Atgl6L1 and NLRP3 were involved in WB analysis; (b) The expression Atg16L1 was detected by Confocal laser analysis.
LC3B: Light chain 3 beta; Atg16L1: Autophagy-related 16 like 1; NLRP3: NOD-like receptor thermal protein domain associated protein; GAPDH: Glyceraldehyde-3- phosphate dehydrogenase; DAPI: Diamidino-2-phenylindole; Ctrl: Control; Si-Atg16L1: SiRNA-Autophagy-related 16 like 1.
Figure 4
Figure 4. The effect of ER on the related gene expression and the direct interaction between ER and NLRP3. (a) Atg16L1 and NLRP3 were involved in RT-qPCR analysis; (b) The direct interaction between ER and NLRP3 was implied by CO-IP analysis.
Atg16L1: Autophagy-related 16 like 1; Ctrl: Control; NLRP3: NOD-like receptor thermal protein domain associated protein; IP: Immunoprecipitation; ER: Estrogen receptor; RT-qPCR: Real-time quantitative polymerase chain reaction.
See this image and copyright information in PMC

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