Bibliographic Details
| Title: |
sdRNA-D43 derived from small nucleolar RNA snoRD43 improves chondrocyte senescence and osteoarthritis progression by negatively regulating PINK1/Parkin-mediated mitophagy pathway via dual-targeting NRF1 and WIPI2. |
| Authors: |
Deng, Zengfa1,2,3,4 (AUTHOR), Li, Changzhao2,5,6 (AUTHOR), Hu, Shu3,4 (AUTHOR), Zhong, Yanlin1,2 (AUTHOR), Li, Wei1,2 (AUTHOR), Lin, Zhencan1,2 (AUTHOR), Mo, Xiaolin1,2 (AUTHOR), Li, Ming1,2 (AUTHOR), Xu, Dongliang2,5 (AUTHOR), Long, Dianbo1,2 (AUTHOR) longdb@mail2.sysu.edu.cn, Mao, Guping1,2 (AUTHOR) maogp@mail2.sysu.edu.cn, Kang, Yan1,2 (AUTHOR) kangyan2@mail.sysu.edu.cn |
| Source: |
Cell Communication & Signaling. 2/11/2025, Vol. 23 Issue 1, p1-21. 21p. |
| Subject Terms: |
*KNEE joint, *GENE expression, *LABORATORY rats, *MEDICAL sciences, *GENETIC regulation |
| Abstract: |
Background: Chondrocyte senescence play an essential role in osteoarthritis (OA) progression. Recent studies have shown that snoRNA-derived RNA fragments (sdRNAs) are novel regulators of post-transcriptional gene expression. However, the expression profiles and their role in post-transcriptional gene regulation in chondrocyte senescence and OA progression is unknown. Here, we determined sdRNAs expression profile and explored sdRNA-D43 role in OA and its mechanism. Methods: We used qPCR arrays to determine sdRNAs expression in the chondrocytes of areas undamaged and damaged of the three knee OA samples. SdRNA-D43 expression was determined using quantitative reverse transcription-polymerase chain reaction and in situ hybridization. Then, bioinformatics analysis was conducted on the target genes that might be silenced by sdRNA-D43. Primary chondrocytes of damaged regions of knee OA samples were transfected with a sdRNA-D43 inhibitor or mimic to determine their functions, including in relation to mitophagy and chondrocyte senescence. Argonaute2-RNA immunoprecipitation and luciferase reporter assays were conducted to determine the target gene of sdRNA-D43. In a rat OA model induced by monosodium iodoacetate, adeno-associated virus sh-rat-sdRNA-D43 was injected into the knee joint cavity to assess its in vivo effects. Results: sdRNA-D43 expression were upregulated in damaged areas of knee OA cartilage with increased senescent chondrocytes. sdRNA-D43 inhibited mitophagy and promoted chondrocytes senescence during OA progression. Mechanistically, sdRNA-D43 silenced the expression of both NRF1 and WIPI2 by binding to their 3′-UTR in an Argonaute2‑dependent manner, which inhibited PINK1/Parkin-mediated pathway. Additionally, injection of AAV-sh-sdRNA-D43 alleviated the progression of OA in a monosodium iodoacetate-induced rat model. Conclusion: Our results reveal an important role for a novel sdRNA-D43 in OA progression. sdRNA-D43 improves chondrocyte senescence by negatively regulating PINK1/Parkin-mediated mitophagy pathway via dual-targeting NRF1 and WIPI2, which provide a potential therapeutic strategy for OA treatment. [ABSTRACT FROM AUTHOR] |
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