LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of β-catenin in BMSCs

Weiqian Jiang; Yu Chen; Mingjie Sun; Xiao Huang; Hongrui Zhang; Zheng Fu; Jingjiang Wang; Shichun Zhang; Chengjie Lian; Boyu Tang; Dulei Xiang; Yange Wang; Yulu Zhang; Changchun Jian; Chaohua Yang; Jun Zhang; Dian Zhang; Tingmei Chen; Jian Zhang

Cell Reports (Aug 2023)

LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of β-catenin in BMSCs

Weiqian Jiang,
Yu Chen,
Mingjie Sun,
Xiao Huang,
Hongrui Zhang,
Zheng Fu,
Jingjiang Wang,
Shichun Zhang,
Chengjie Lian,
Boyu Tang,
Dulei Xiang,
Yange Wang,
Yulu Zhang,
Changchun Jian,
Chaohua Yang,
Jun Zhang,
Dian Zhang,
Tingmei Chen,
Jian Zhang

Affiliations

Weiqian Jiang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Yu Chen: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Mingjie Sun: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Xiao Huang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Hongrui Zhang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Zheng Fu: Department of Orthopedics, Binzhou People’s Hospital, Binzhou, Shandong Province, China
Jingjiang Wang: Department of Orthopedics, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Shichun Zhang: Department of Orthopedics, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Chengjie Lian: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Boyu Tang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Dulei Xiang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Yange Wang: Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Yulu Zhang: Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Changchun Jian: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Chaohua Yang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Jun Zhang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Dian Zhang: Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Tingmei Chen: Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Jian Zhang: Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Corresponding author

Journal volume & issue: Vol. 42, no. 8
p. 112969

Abstract

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Summary: The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of β-catenin. Ultimately, the nuclear localization of β-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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