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Updated: Jul 19, 2025

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

Weiqian Jiang1, Yu Chen1, Mingjie Sun1

  • 1Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Cell Reports
|August 13, 2023
PubMed

Insights

A novel peptide, RIP, derived from lncRNA DGCR5, promotes bone marrow mesenchymal stem cell (BMSC) adipogenesis and worsens steroid-induced osteonecrosis of the femoral head (SONFH). Targeting RIP may offer a therapeutic strategy for SONFH.

Area of Science:

  • Molecular Biology
  • Stem Cell Biology
  • Orthopedics

Background:

  • Steroid-induced osteonecrosis of the femoral head (SONFH) progression is linked to bone marrow mesenchymal stem cell (BMSC) differentiation.
  • Long non-coding RNAs (lncRNAs) play roles in cellular differentiation, but their specific functions in SONFH are not fully understood.

Purpose of the Study:

  • To investigate the role of lncRNA DGCR5 and its encoded peptide in BMSC differentiation and SONFH pathogenesis.
  • To identify potential therapeutic targets for SONFH.

Main Methods:

  • In vitro studies on BMSC differentiation.
  • Molecular mechanism analysis involving RIP, RAC1, PAK1, and β-catenin.
  • In vivo experiments using a rat model of SONFH.

Main Results:

  • lncRNA DGCR5 encodes a polypeptide named RIP (Rac1 inactivated peptide).
  • RIP promotes BMSC adipogenic differentiation and exacerbates SONFH.
  • RIP inactivates the RAC1/PAK1 cascade by binding to RAC1, reducing β-catenin phosphorylation and nuclear localization.
  • Overexpression of RIP in rats led to bone disorder and adipocyte accumulation, which was reversed by RAC1 overexpression.

Conclusions:

  • RIP, a peptide encoded by lncRNA DGCR5, drives BMSC adipogenesis and worsens SONFH by inhibiting the RAC1/PAK1/β-catenin pathway.
  • RIP represents a potential therapeutic target for managing steroid-induced osteonecrosis of the femoral head.
Keywords:
CP: Molecular biologyCP: Stem cell research

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