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ABSTRACT
Background
Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear.
Methods
Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets.
Results
The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11–7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge.
Conclusions
This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach.
Abbreviations
| OA | = | Osteoarthritis |
| SF | = | Synovial Fluid |
| DEPs | = | Differentially expressed proteins |
| GO | = | Gene Ontology |
| KEGG | = | Kyoto Encyclopedia of Genes and Genomes |
| BFA | = | Brefeldin A |
| IL-1β | = | Interleukin-1 beta |
| IL-6 | = | Interleukin-6 |
| TNF-α | = | Tumor Necrosis Factor-Alpha |
| INOS | = | Inducible Nitric Oxide Synthase |
| IHC | = | Immunohistochemistry |
| IF | = | Immunofluorescence |
| M1 | = | Classically Activated Macrophage |
| M2 | = | Alternatively Activated Macrophage |
| ceRNA | = | Competing Endogenous RNA |
| miRNA | = | Micro RNA |
| lncRNA | = | Long non-coding RNA |
| NF-κB | = | Nuclear Factor Kappa B |
| WB | = | Western Blot |
| ELISA | = | Enzyme-linked Immunosorbent Assay |
| BCA | = | Bicinchoninic Acid |
| SDS-PAGE | = | Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis |
| PVDF | = | Polyvinylidene Fluoride |
| TBST | = | Tris-buffered Saline and Tween 20 |
| DAPI | = | 4,’6-diamidino-2-phenylindole |
| ECL | = | Enhanced Chemiluminescence |
| SD | = | Standard Deviation |
| SEM | = | Standard Error of the Mean |
| ANOVA | = | Analysis of Variance |
| t-test | = | Student’s t-test |
Acknowledgments
The authors would like to thank all the participating patients.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Availability of data and materials
Data generated or analyzed during this study are included in this published article and its supplementary files.
Authors’ contributions
YZ: study design, manuscript writing. ZHL: data collection, review. CC: data analysis. HH: samples collection. ZDL, HCZ, and WBH: data interpretation. WW, BL, and YFY: review. All authors contributed to the article and approved the submitted version.
Consent for publication
Written informed consent was obtained from all participants.
Ethics approval and consent to participate
The study was reviewed and approved by the Institutional Review Board of Shanghai Tongji Hospital (No. SBKT-2023-099).
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/03008207.2024.2310852.