IRF1 regulates apoptosis and osteogenic differentiation of bone marrow mesenchymal stem cells and ameliorates osteoporosis by activating the PI3K/AKT signaling pathway

作者：Menglong Hu, Erfan Wei, Likun Wu, Xingtong Pan, Qiyue Zhu, Xiuyun Xu, Xinyi Dong, Weiliang Wu, Hao Liu, Yunsong Liu · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.11.037 · 被引用次数：5 · 研究领域：Bone Metabolism and Diseases、TGF-β signaling in diseases、Bone health and osteoporosis research

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are a critical cell type for stem cell-based bone regenerative therapy. Promoting osteogenic differentiation of BMSCs is important for the promotion of bone formation. Interferon regulatory factor 1 (IRF1) was discovered as an essential factor in immune responses and the differentiation of several cell lines. Nevertheless, the potential of IRF1 as a therapeutic target for the modulation of BMSCs in the context of bone regeneration strategies remains unexplored. Here, we investigated the role of IRF1 in BMSC fate determination and demonstrated IRF1 as a promising target for osteoporosis. METHODS: Irf1-overexpressing and Irf1-knockdown murine BMSCs (mBMSCs) were established by plasmid and lentivirus transfection, and the expression efficiency was verified. The role of IRF1 in regulating the proliferation, migration, apoptosis, and osteogenic differentiation of mBMSCs in vitro was investigated using gain- and loss-of-function experiments. In addition, Irf1-overexpressing mBMSCs were implanted subcutaneously with scaffold material into the backs of nude mice to evaluate the ectopic osteogenesis capability in vivo. Irf1-overexpressing mBMSCs were injected into the tail vein of ovariectomized and aging-related osteoporosis mouse models to evaluate their therapeutic effects. In addition, the underlying mechanisms were explored by RNA sequencing and validated through real-time reverse transcription-polymerase chain reaction (RT-P...