The Long Noncoding RNA TUG1 Is Down-Regulated in Osteonecrosis of the Femoral Head and Enhances the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Stimulating the Wnt/β-Catenin Pathway

Abstract

Osteonecrosis of the femoral head (ONFH) is an orthopaedic disease with multifaceted pathogenesis. The role of long noncoding RNA (lncRNA) taurine-up-regulated gene 1 (TUG1) in ONFH remains unexplored. Thus, lncRNA expression profiles in subchondral bone from patients with ONFH and healthy controls were analyzed using microarray analysis, RT-qPCR, and bioinformatics. To evaluate the effect of TUG1 on osteogenic differentiation, TUG1 was overexpressed or knocked down in human bone marrow mesenchymal stem cells (hBMSCs), assessed via quantitative RT-PCR, Western blot analysis, and staining assays. In vivo, TUG1 was knocked down using adeno-associated viruses in a rat ONFH model. Micro–computed tomography, histology, enzyme-linked immunosorbent assay, quantitative RT-PCR, and immunohistochemistry were used to assess bone mass and osteogenic markers. TUG1 was significantly down-regulated in ONFH subchondral bone. Overexpression of TUG1 in hBMSCs up-regulated osteogenesis-related genes and proteins (runt-related transcription factor 2, osteopontin, osteocalcin, collagen type I alpha 1 chain, bone morphogenetic protein 2, and β-catenin), enhanced alkaline phosphatase activity, and increased mineralization. Conversely, TUG1 knockdown reduced these markers. In vivo, TUG1 knockdown disrupted bone microstructure and decreased osteogenic marker expression in the femoral head. This study revealed that TUG1 is down-regulated in ONFH subchondral bone, leading to osteogenic dysfunction through the Wnt/β-catenin pathway. It provided a better understanding of lncRNA's regulatory role in local osteonecrosis and offered new insights into ONFH pathogenesis. This study provides a reference for future research and treatment strategies.