ISSN: 1838-7640Theranostics
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Theranostics 2023; 13(15):5207-5222. doi:10.7150/thno.89033 This issue Cite
Research Paper
Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice
1. Department of Biological Sciences, College of Health Sciences, Wonkwang University; Iksan, Chunbuk, 570-749, Korea.
2. Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University; Seoul 03760, Korea.
3. Department of Chemical and Biological Engineering, Korea National University of Transportation; Chungju 27469, Korea.
4. Department of Carbon Convergence Engineering, Wonkwang University; Iksan, Chunbuk, 570-749, Korea.
†These authors contributed equally.
Citation:
Song J, Kim EH, Yang JH, Kim D, Robby AI, Kim Sa, Park SY, Ryu JH, Jin EJ. Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice. Theranostics 2023; 13(15):5207-5222. doi:10.7150/thno.89033. https://www.thno.org/v13p5207.htm
Other stylesAbstract
Rationale: One of the hallmarks of osteoarthritis (OA), the most common degenerative joint disease, is increased numbers of senescent chondrocytes. Targeting senescent chondrocytes or signaling mechanisms leading to senescence could be a promising new therapeutic approach for OA treatment. However, understanding the key targets and links between chondrocyte senescence and OA remains unclear.
Methods: Senescent chondrocytes were identified from Nudt7-/-, Acot12-/-, double-knockout mice lacking Acot12 and Nudt7 (dKO) and applied to microarray. The presence of forkhead transcription factor M1 (FOXM1) was detected in aged, dKO, and destabilization of the medial meniscus (DMM) cartilages and articular chondrocytes, and the effect of FoxM1 overexpression and acetyl-CoA treatment on cartilage homeostasis was examined using immunohistochemistry, quantitative real-time PCR (qRT-PCR), cell apoptosis and proliferation assay, and safranin O staining. Delivery of Rho@PAA-MnO2 (MnO2 nanosheet) or heparin-ACBP/COS-GA-siFoxM1 (ACBP-siFoxM1) nanoparticles into DMM cartilage was performed.
Results: Here, we propose the specific capture of acetyl-CoA with the delivery of (FoxM1 siRNA (siFoxM1) to prevent cartilage degradation by inhibiting the axis of chondrocyte senescence. dKO stimulate chondrocyte senescence via the upregulation of FoxM1 and contribute to severe cartilage breakdown. We found that the accumulation of acetyl-CoA in the dKO mice may be responsible for the upregulation of FoxM1 during OA pathogenesis. Moreover, scavenging reactive oxygen species (ROS) induced by chondrocyte senescence via the implantation of MnO2 nanosheets or delivery of siFoxM1 functionalized with acetyl-CoA binding protein (ACBP) to capture acetyl-CoA using an injectable bioactive nanoparticle (siFoxM1-ACBP-NP) significantly suppressed DMM-induced cartilage destruction.
Conclusion: We found that the loss of Acot12 and Nudt7 stimulates chondrocyte senescence via the upregulation of FoxM1 and accumulation of acetyl-CoA, and the application of siFoxM1-ACBP-NP is a potential therapeutic strategy for OA treatment.
Keywords: osteoarthritis, Acot12-/-Nudt7-/-, FoxM1, Rho@PAA-MnO2, heparin-ACBP/COS-GA-siFoxM1
Citation styles
APA
Song, J., Kim, E.H., Yang, J.H., Kim, D., Robby, A.I., Kim, S.a., Park, S.Y., Ryu, J.H., Jin, E.J. (2023). Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice. Theranostics, 13(15), 5207-5222. https://doi.org/10.7150/thno.89033.
ACS
Song, J.; Kim, E.H.; Yang, J.H.; Kim, D.; Robby, A.I.; Kim, S.a.; Park, S.Y.; Ryu, J.H.; Jin, E.J. Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice. Theranostics 2023, 13 (15), 5207-5222. DOI: 10.7150/thno.89033.
NLM
Song J, Kim EH, Yang JH, Kim D, Robby AI, Kim Sa, Park SY, Ryu JH, Jin EJ. Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice. Theranostics 2023; 13(15):5207-5222. doi:10.7150/thno.89033. https://www.thno.org/v13p5207.htm
CSE
Song J, Kim EH, Yang JH, Kim D, Robby AI, Kim Sa, Park SY, Ryu JH, Jin EJ. 2023. Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice. Theranostics. 13(15):5207-5222.
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