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<p>Osteoporosis is one of the most common bone-related diseases in which osteogenic differentiation plays a key role. Adipose-derived mesenchymal stem cells (ADMSCs), as one of the important sources of bone formation, can differentiate into osteoblasts under appropriate conditions. To investigate the effect and potential mechanism of ZFP36 on osteogenic differentiation of ADMSCs in osteoporosis by regulating the stability of KLF3 mRNA. In this study, an osteoporosis rat model was established by ovariectomy (OVX), and the expression level of KLF3 in bone tissue was detected by RT-qPCR and immunohistochemistry (IHC). To further investigate the effect of KLF3 gene knockdown on bone health in osteoporotic rats. In vitro, KLF3 over-expression was performed on ADMSCs, and the effect of KLF3 knockdown on osteogenic differentiation of ADMSCs was evaluated by alkaline phosphatase (ALP) activity assay and alizarin red S staining. In addition, RNA pull-down, dual luciferase reporter gene, RIP and Actinomycin D treatment were used to explore the regulatory mechanism of ZFP36-mediated KLF3 mRNA degradation in osteogenic differentiation. Finally, the effect of ZFP36 on osteogenic differentiation and its interaction with KLF3 were further verified by interfering with ZFP36/KLF3 expression in rats in vivo and in vitro. In the osteoporotic rat model, KLF3 expression was significantly downregulated in bone tissue. Over-expression of KLF3 in ADMSCs significantly increased KLF3 protein level but inhibited osteogenic differentiation. In contrast, the over-expression of ZFP36 significantly promoted the osteogenic differentiation of ADMSCs, and the expression level of KLF3 was significantly reduced under this condition. ZFP36 accelerates KLF3 degradation by directly binding KLF3 mRNA. Inhibition of ZFP36 inhibited osteogenic differentiation of cells by up-regulating KLF3, and osteogenic differentiation was promoted after KLF3 knockdown. In animal experiments, over-expression of ZFP36 significantly improved BMD, bone volume, and trabecular bone architecture in osteoporotic rats, while over-expression of KLF3 reversed these improvements. ZFP36 promotes the osteogenic differentiation of ADMSCs by mediating the degradation of KLF3 mRNA and provides a potential molecular target for the treatment of osteoporosis.</p>

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ZFP36 regulates the osteogenic differentiation of adipose-derived mesenchymal stem cells in osteoporosis by mediating KLF3 mRNA degradation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月24日

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  • Chao Liu,
  • Ming Yi,
  • Bangmin Luo,
  • Ming Wang

摘要

Osteoporosis is one of the most common bone-related diseases in which osteogenic differentiation plays a key role. Adipose-derived mesenchymal stem cells (ADMSCs), as one of the important sources of bone formation, can differentiate into osteoblasts under appropriate conditions. To investigate the effect and potential mechanism of ZFP36 on osteogenic differentiation of ADMSCs in osteoporosis by regulating the stability of KLF3 mRNA. In this study, an osteoporosis rat model was established by ovariectomy (OVX), and the expression level of KLF3 in bone tissue was detected by RT-qPCR and immunohistochemistry (IHC). To further investigate the effect of KLF3 gene knockdown on bone health in osteoporotic rats. In vitro, KLF3 over-expression was performed on ADMSCs, and the effect of KLF3 knockdown on osteogenic differentiation of ADMSCs was evaluated by alkaline phosphatase (ALP) activity assay and alizarin red S staining. In addition, RNA pull-down, dual luciferase reporter gene, RIP and Actinomycin D treatment were used to explore the regulatory mechanism of ZFP36-mediated KLF3 mRNA degradation in osteogenic differentiation. Finally, the effect of ZFP36 on osteogenic differentiation and its interaction with KLF3 were further verified by interfering with ZFP36/KLF3 expression in rats in vivo and in vitro. In the osteoporotic rat model, KLF3 expression was significantly downregulated in bone tissue. Over-expression of KLF3 in ADMSCs significantly increased KLF3 protein level but inhibited osteogenic differentiation. In contrast, the over-expression of ZFP36 significantly promoted the osteogenic differentiation of ADMSCs, and the expression level of KLF3 was significantly reduced under this condition. ZFP36 accelerates KLF3 degradation by directly binding KLF3 mRNA. Inhibition of ZFP36 inhibited osteogenic differentiation of cells by up-regulating KLF3, and osteogenic differentiation was promoted after KLF3 knockdown. In animal experiments, over-expression of ZFP36 significantly improved BMD, bone volume, and trabecular bone architecture in osteoporotic rats, while over-expression of KLF3 reversed these improvements. ZFP36 promotes the osteogenic differentiation of ADMSCs by mediating the degradation of KLF3 mRNA and provides a potential molecular target for the treatment of osteoporosis.