Related Experiment Video
Updated: Jun 21, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Targeting the senescence-related genes MAPK12 and FOS to alleviate osteoarthritis
Nana Geng1, Menglin Xian1, Lin Deng1
1State Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
Background:
The mechanism by which chondrocyte senescence aggravate OA progression has not yet been well elucidated. The aim of this study was to investigate the chondrocyte senescence related gene biosignatures in OA, and to analyze on the underlying mechanisms of senescence in OA.
Materials And Methods:
We intersected osteoarthritis dataset GSE82107 from GEO database and senescence dataset from CellAge database of human senescence-associated genes based on genetic manipulations experiments plus gene expression profilin, and screened out 4 overlapping genes. The hub genes were verified in vitro and in human OA cartilage tissues by qRT-PCR. We further confirmed the function of mitogen-activated protein kinase 12 (MAPK12) and Fos proto-oncogene (FOS) in OA in vitro and in vivo by qRT-PCR, western blotting, Edu staining, immunofluorescence, SA-β-gal staining, HE, IHC, von frey test, and hot plate.
Results:
1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated. The expression of MAPK12 was obviously downregulated, whereas the expression profiles of FOS, CYR61 and TNFSF15 were remarkedly upregulated in H2O2- or IL-1β-stimulated C28/I2 cells, human OA cartilage tissues, and knee cartilage of aging mice. Furthermore, both MAPK12 over-expression and FOS knock-down can promote cell proliferation and cartilage anabolism, inhibit cell senescence and cartilage catabolism, relieve joint pain in H2O2- or IL-1β-stimulated C28/I2 cells and mouse primary chondrocytes, destabilization of the medial meniscus (DMM) mice.
Conclusion:
This study explored that MAPK12 and FOS are involved in the occurrence and development of OA through modulating chondrocyte senescence. They might be biomarkers of OA chondrocyte senescence, and provides some evidence as subsequent possible therapeutic targets for OA.
The Translational Potential Of This Article:
The translation potential of this article is that we revealed MAPK12 and FOS can effectively alleviate OA by regulating chondrocyte senescence, and thus provided potential therapeutic targets for prevention or treatment of OA in the future.
Insights
This study identifies MAPK12 and FOS as key genes in osteoarthritis (OA) progression by modulating chondrocyte senescence. Targeting these genes may offer new therapeutic strategies for OA.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Chondrocyte senescence is implicated in osteoarthritis (OA) progression, but the underlying mechanisms remain unclear.
- Investigating senescence-related gene biosignatures in OA is crucial for understanding disease development.
Purpose of the Study:
- To identify and analyze chondrocyte senescence-related gene biosignatures in OA.
- To elucidate the mechanisms of senescence in OA pathogenesis.
Main Methods:
- Intersected OA and human senescence gene datasets to identify overlapping genes.
- Validated hub genes (MAPK12, FOS, CYR61, TNFSF15) in vitro and in human OA cartilage.
- Confirmed the functional roles of MAPK12 and FOS in OA models using various molecular and histological techniques.
Main Results:
- Identified four overlapping genes: FOS, CYR61, TNFSF15 (upregulated) and MAPK12 (downregulated).
- Observed altered expression of these genes in OA cells, human OA cartilage, and aging mouse cartilage.
- Demonstrated that MAPK12 overexpression and FOS knockdown inhibit senescence, promote cartilage health, and alleviate pain in OA models.
Conclusions:
- MAPK12 and FOS play significant roles in OA development by modulating chondrocyte senescence.
- These genes represent potential biomarkers for OA chondrocyte senescence.
- MAPK12 and FOS offer promising therapeutic targets for OA treatment.
