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
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.
