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LncRNA DGCR5-encoded polypeptide RIP aggravates steroid-induced osteonecrosis of the femoral head by repressing nuclear localization of β-catenin in BMSCs

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-aa 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.

ORGANISM(S): Rattus Rattus

SUBMITTER: Jian Zhang

PROVIDER: PXD043889 | iProX | Wed Jul 19 00:00:00 BST 2023

REPOSITORIES: iProX

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