Nuclear receptor Rev-erbα alleviates intervertebral disc degeneration by recruiting NCoR-HDAC3 co-repressor and inhibiting NLRP3 inflammasome.

Autor: Zhou Q; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Pu X; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Qian Z; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Chen H; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Wang N; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Wang S; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Feng Z; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Zhu Z; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Wang B; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Qiu Y; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Sun X; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2024 Dec; Vol. 57 (12), pp. e13720. Date of Electronic Publication: 2024 Jul 24.
DOI: 10.1111/cpr.13720
Abstrakt: Intervertebral discs (IVDs) are rhythmic tissues that experience daily low-load recovery. Notably, aging and abnormal mechanical stress predispose IVDs to degeneration due to dysrhythmia-induced disordered metabolism. Meanwhile, Rev-erbα acts as a transcriptional repressor in maintaining biorhythms and homeostasis; however, its function in IVD homeostasis and degeneration remains unclear. This study assessed the relationship between low Rev-erbα expression levels and IVD degeneration. Rev-erbα deficiency accelerated needle puncture or aging-induced IVD degeneration, characterized by increased extracellular matrix (ECM) catabolism and nucleus pulposus (NP) cell apoptosis. Mechanistically, Rev-erbα knockdown in NP cells aggravated rhIL1β-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, exacerbating the imbalanced ECM and NP cell apoptosis. Meanwhile, blocking NLRP3 inflammasome activation mitigated Rev-erbα deficiency and needle puncture-induced IVD degeneration. Particularly, Rev-erbα mediated the transcriptional repression of the NLRP3 inflammasome via the ligand heme-binding of nuclear receptor co-repressor (NCoR) and histone deacetylase 3 (HDAC3) complex. Thus, the increased expression of Rev-erbα in NP cells following short-term rhIL1β treatment failed to inhibit NLRP3 transcription in vitro owing to heme depletion. Pharmacological activation of Rev-erbα in vivo and in vitro alleviated IVD degeneration by altering the NLRP3 inflammasome. Taken together, targeting Rev-erbα may be a potential therapeutic strategy for alleviating IVD degeneration and its related diseases.
(© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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