دورية أكاديمية
أعرض في EDS

Abnormal stress promotes intervertebral disc degeneration through WTAP/YTHDF2-dependent TIMP3 m6A modification.

التفاصيل البيبلوغرافية
العنوان: Abnormal stress promotes intervertebral disc degeneration through WTAP/YTHDF2-dependent TIMP3 m6A modification.
المؤلفون: Gao D; Department of Spine Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China., Zhao Q; Department of Spine Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China., Liu C; Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu, Anhui, China., Zhang Y; Spine Research Center of Wannan Medical College, Wuhu, Anhui, China., Xiao L; Spine Research Center of Wannan Medical College, Wuhu, Anhui, China.
المصدر: Journal of cellular physiology [J Cell Physiol] 2024 May; Vol. 239 (5), pp. e31219. Date of Electronic Publication: 2024 Feb 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0050222 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4652 (Electronic) Linking ISSN: 00219541 NLM ISO Abbreviation: J Cell Physiol Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Wiley-Liss
Original Publication: Philadelphia, Wistar Institute of Anatomy and Biology.
مواضيع طبية MeSH: Intervertebral Disc Degeneration*/genetics , Intervertebral Disc Degeneration*/metabolism , Intervertebral Disc Degeneration*/pathology , Nucleus Pulposus*/metabolism , Nucleus Pulposus*/pathology , RNA-Binding Proteins*/genetics , RNA-Binding Proteins*/metabolism , Stress, Mechanical* , Tissue Inhibitor of Metalloproteinase-3*/genetics , Tissue Inhibitor of Metalloproteinase-3*/metabolism , Adenosine*/analogs & derivatives , RNA Splicing Factors*/metabolism , Cell Cycle Proteins*/metabolism, Animals ; Female ; Humans ; Male ; Middle Aged ; Rats ; Extracellular Matrix/metabolism ; Rats, Sprague-Dawley
مستخلص: Mechanical environment worsening is an important predisposing factor that accelerates intervertebral disc degeneration (IDD), but its specific regulatory mechanisms remain unclear. In this study, we reveal the molecular mechanisms of WTAP/YTHDF2-mediated m6A modification in abnormal stress-induced intervertebral disc (IVD) matrix degradation. WTAP expression in human nucleus pulposus cells was elevated under tension. Similarly, high WTAP expression was detected in severe degenerated human and rat nucleus pulposus tissues. Functionally, WTAP was found to increase the TIMP3 transcript methylation level under tension, resulting in YTHDF2 recognition, binding, and induction of its degradation. Reduction in TIMP3 caused increases in active matrix metalloproteinases, ultimately inducing extracellular matrix degradation in nucleus pulposus cells. Macroscopically, this promotes IDD. Additionally, in vitro and in vivo inhibition of WTAP expression or TIMP3 overexpression significantly increased stress resistance in the nucleus pulposus, thereby alleviating IDD. Our results show that abnormal stress disrupts IVD matrix stability through WTAP/YTHDF2-dependent TIMP3 m6A modification.
(© 2024 Wiley Periodicals LLC.)
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معلومات مُعتمدة: 82002358 National Natural Science Foundation of China
فهرسة مساهمة: Keywords: extracellular matrix; intervertebral disc degeneration; m6A methylation; nucleus pulposus cells; stress
المشرفين على المادة: 0 (RNA-Binding Proteins)
0 (Tissue Inhibitor of Metalloproteinase-3)
CLE6G00625 (N-methyladenosine)
K72T3FS567 (Adenosine)
0 (WTAP protein, human)
0 (RNA Splicing Factors)
0 (Cell Cycle Proteins)
0 (YTHDF2 protein, human)
0 (TIMP3 protein, human)
تواريخ الأحداث: Date Created: 20240212 Date Completed: 20240515 Latest Revision: 20240531
رمز التحديث: 20240601
DOI: 10.1002/jcp.31219
PMID: 38345407
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-4652
DOI:10.1002/jcp.31219