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Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
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N6-Methyladenosine-Modified circSMAD4 Prevents Lumbar Instability Induced Cartilage Endplate Ossification
Hanwen Li1, Yingchuang Tang1, Sihan Hu2
1Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 12, 2025
Summary
Stabilizing circSMAD4, a circular RNA, prevents cartilage endplate degeneration caused by lumbar instability. This process involves m6A modification and regulates Yap1 mRNA, offering a potential therapy for disc degeneration.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Lumbar instability leads to cartilage endplate ossification and intervertebral disc degeneration.
- CircSMAD4, a circRNA related to Yap1, is downregulated under stress.
Purpose of the Study:
- To investigate the role of circSMAD4 in maintaining endplate cartilage homeostasis under abnormal stress.
- To elucidate the regulatory mechanism of circSMAD4 in preventing cartilage degeneration.
Main Methods:
- In vitro knockdown and overexpression of circSMAD4.
- Transcriptome sequencing and mass spectrometry.
- AAV5-mediated circSMAD4 delivery in vivo.
- Yap1 knockout mouse model.
Main Results:
- circSMAD4 knockdown degraded Yap1 mRNA; overexpression enhanced Yap1 expression and nuclear translocation.
- METTL14-mediated m6A modification stabilizes circSMAD4 expression.
- circSMAD4 regulates Yap1 mRNA via the m6A reader IGF2BP1, promoting nuclear translocation and chondrocyte protection.
- circSMAD4 overexpression rescued LSI-induced degeneration, but Yap1 knockout mice did not show rescue.
Conclusions:
- m6A-modified circSMAD4 stabilizes Yap1 mRNA expression and translocation, preventing cartilage endplate degeneration under stress.
- circSMAD4 represents a potential therapeutic target for instability-induced intervertebral disc degeneration.
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