Circular RNA Gtdc1 Protects Against Offspring Osteoarthritis Induced by Prenatal Prednisone Exposure by Regulating SRSF1-Fn1 Signaling
© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH..
Chondrodysplasia is closely associated with low birth weight and increased susceptibility to osteoarthritis in adulthood. Prenatal prednisone exposure (PPE) can cause low birth weight; however, its effect on offspring cartilage development remains unexplored. Herein, rats are administered clinical doses of prednisone intragastrically on gestational days (GDs) 0-20 and underwent long-distance running during postnatal weeks (PWs) 24-28. Knee cartilage is assayed for quality and related index changes on GD20, PW12, and PW28. In vitro experiments are performed to elucidate the mechanism. PPE decreased cartilage proliferation and matrix synthesis, causing offspring chondrodysplasia. Following long-distance running, the PPE group exhibited more typical osteoarthritis-like changes. Molecular analysis revealed that PPE caused cartilage circRNomics imbalance in which circGtdc1 decreased most significantly and persisted postnatally. Mechanistically, prednisolone reduced circGtdc1 expression and binding with Srsf1 to promote degradation of Srsf1 via K48-linked polyubiquitination. This further inhibited the formation of EDA/B+Fn1 and activation of PI3K/AKT and TGFβ pathways, reducing chondrocyte proliferation and matrix synthesis. Finally, intra-articular injection of offspring with AAV-circGtdc1 ameliorated PPE-induced chondrodysplasia, but this effect is reversed by Srsf1 knockout. Altogether, this study confirms that PPE causes chondrodysplasia and susceptibility to osteoarthritis by altering the circGtdc1-Srsf1-Fn1 axis; in vivo, overexpression of circGtdc1 can represent an effective intervention target for ameliorating PPE-induced chondrodysplasia.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - (2024) vom: 22. März, Seite e2307442 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Liang [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Alternative RNA splicing |
|---|
| Anmerkungen: |
Date Revised 23.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1002/advs.202307442 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370096460 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370096460 | ||
| 003 | DE-627 | ||
| 005 | 20240324235330.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240324s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/advs.202307442 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1345.xml |
| 035 | |a (DE-627)NLM370096460 | ||
| 035 | |a (NLM)38520084 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Liang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Circular RNA Gtdc1 Protects Against Offspring Osteoarthritis Induced by Prenatal Prednisone Exposure by Regulating SRSF1-Fn1 Signaling |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 23.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH. | ||
| 520 | |a Chondrodysplasia is closely associated with low birth weight and increased susceptibility to osteoarthritis in adulthood. Prenatal prednisone exposure (PPE) can cause low birth weight; however, its effect on offspring cartilage development remains unexplored. Herein, rats are administered clinical doses of prednisone intragastrically on gestational days (GDs) 0-20 and underwent long-distance running during postnatal weeks (PWs) 24-28. Knee cartilage is assayed for quality and related index changes on GD20, PW12, and PW28. In vitro experiments are performed to elucidate the mechanism. PPE decreased cartilage proliferation and matrix synthesis, causing offspring chondrodysplasia. Following long-distance running, the PPE group exhibited more typical osteoarthritis-like changes. Molecular analysis revealed that PPE caused cartilage circRNomics imbalance in which circGtdc1 decreased most significantly and persisted postnatally. Mechanistically, prednisolone reduced circGtdc1 expression and binding with Srsf1 to promote degradation of Srsf1 via K48-linked polyubiquitination. This further inhibited the formation of EDA/B+Fn1 and activation of PI3K/AKT and TGFβ pathways, reducing chondrocyte proliferation and matrix synthesis. Finally, intra-articular injection of offspring with AAV-circGtdc1 ameliorated PPE-induced chondrodysplasia, but this effect is reversed by Srsf1 knockout. Altogether, this study confirms that PPE causes chondrodysplasia and susceptibility to osteoarthritis by altering the circGtdc1-Srsf1-Fn1 axis; in vivo, overexpression of circGtdc1 can represent an effective intervention target for ameliorating PPE-induced chondrodysplasia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a alternative RNA splicing | |
| 650 | 4 | |a chondrodysplasia | |
| 650 | 4 | |a circular RNA | |
| 650 | 4 | |a osteoarthritis | |
| 650 | 4 | |a prenatal prednisone exposure | |
| 700 | 1 | |a Hong, Yuntian |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qingxian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a He, Hangyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jiayong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Liaobin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Advanced science (Weinheim, Baden-Wurttemberg, Germany) |d 2014 |g (2024) vom: 22. März, Seite e2307442 |w (DE-627)NLM252851455 |x 2198-3844 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:22 |g month:03 |g pages:e2307442 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/advs.202307442 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 22 |c 03 |h e2307442 | ||