2. Academic Validation
  3. LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of β-catenin in BMSCs

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

  • Cell Rep. 2023 Aug 12;42(8):112969. doi: 10.1016/j.celrep.2023.112969.
Weiqian Jiang 1,  Yu Chen 1,  Mingjie Sun 1,  Xiao Huang 1,  Hongrui Zhang 1,  Zheng Fu 2,  Jingjiang Wang 3,  Shichun Zhang 3,  Chengjie Lian 1,  Boyu Tang 1,  Dulei Xiang 1,  Yange Wang 4,  Yulu Zhang 4,  Changchun Jian 1,  Chaohua Yang 1,  Jun Zhang 1,  Dian Zhang 4,  Tingmei Chen 4,  Jian Zhang 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Orthopedics, Binzhou People's Hospital, Binzhou, Shandong Province, China.
  • 3 Department of Orthopedics, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
  • 5 Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 37573506 DOI: 10.1016/j.celrep.2023.112969
Abstract

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.

Keywords

CP: Molecular biology; CP: Stem cell research.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-102078
    99.76%, Rac1-GEF Interaction Inhibitor