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.
| 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. |
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| 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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| Items | – Name: Title Label: Title Group: Ti Data: 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. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Deng%2C+Zengfa%22">Deng, Zengfa</searchLink><relatesTo>1,2,3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Changzhao%22">Li, Changzhao</searchLink><relatesTo>2,5,6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hu%2C+Shu%22">Hu, Shu</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhong%2C+Yanlin%22">Zhong, Yanlin</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Wei%22">Li, Wei</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lin%2C+Zhencan%22">Lin, Zhencan</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mo%2C+Xiaolin%22">Mo, Xiaolin</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Ming%22">Li, Ming</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xu%2C+Dongliang%22">Xu, Dongliang</searchLink><relatesTo>2,5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Long%2C+Dianbo%22">Long, Dianbo</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> longdb@mail2.sysu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Mao%2C+Guping%22">Mao, Guping</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> maogp@mail2.sysu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Kang%2C+Yan%22">Kang, Yan</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> kangyan2@mail.sysu.edu.cn</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Cell+Communication+%26+Signaling%22">Cell Communication & Signaling</searchLink>. 2/11/2025, Vol. 23 Issue 1, p1-21. 21p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22KNEE+joint%22">KNEE joint</searchLink><br />*<searchLink fieldCode="DE" term="%22GENE+expression%22">GENE expression</searchLink><br />*<searchLink fieldCode="DE" term="%22LABORATORY+rats%22">LABORATORY rats</searchLink><br />*<searchLink fieldCode="DE" term="%22MEDICAL+sciences%22">MEDICAL sciences</searchLink><br />*<searchLink fieldCode="DE" term="%22GENETIC+regulation%22">GENETIC regulation</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Cell Communication & Signaling is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1186/s12964-024-01975-2 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 21 StartPage: 1 Subjects: – SubjectFull: KNEE joint Type: general – SubjectFull: GENE expression Type: general – SubjectFull: LABORATORY rats Type: general – SubjectFull: MEDICAL sciences Type: general – SubjectFull: GENETIC regulation Type: general Titles: – TitleFull: 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. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Deng, Zengfa – PersonEntity: Name: NameFull: Li, Changzhao – PersonEntity: Name: NameFull: Hu, Shu – PersonEntity: Name: NameFull: Zhong, Yanlin – PersonEntity: Name: NameFull: Li, Wei – PersonEntity: Name: NameFull: Lin, Zhencan – PersonEntity: Name: NameFull: Mo, Xiaolin – PersonEntity: Name: NameFull: Li, Ming – PersonEntity: Name: NameFull: Xu, Dongliang – PersonEntity: Name: NameFull: Long, Dianbo – PersonEntity: Name: NameFull: Mao, Guping – PersonEntity: Name: NameFull: Kang, Yan IsPartOfRelationships: – BibEntity: Dates: – D: 11 M: 02 Text: 2/11/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 1478811X Numbering: – Type: volume Value: 23 – Type: issue Value: 1 Titles: – TitleFull: Cell Communication & Signaling Type: main |
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