Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into several tissues, such as bone, cartilage, and fat. Glucocorticoids affect a variety of biological processes such as proliferation, differentiation, and apoptosis of various cell types, including osteoblasts, adipocytes, or chondrocytes. Glucocorticoids exert their function by binding to the glucocorticoid receptor (GR). Physiological concentrations of glucocorticoids stimulate osteoblast proliferation and promote osteogenic differentiation of MSCs. However, pharmacological concentrations of glucocorticoids can not only induce apoptosis of osteoblasts and osteocytes but can also reduce proliferation and inhibit the differentiation of osteoprogenitor cells. Several signaling pathways, including the Wnt, TGFβ/BMP superfamily and Notch signaling pathways, transcription factors, post-transcriptional regulators, and other regulators, regulate osteoblastogenesis and adipogenesis of MSCs mediated by GR. These signaling pathways target key transcription factors, such as Runx2 and TAZ for osteogenesis and PPARγ and C/EBPs for adipogenesis. Glucocorticoid-induced osteonecrosis and osteoporosis are caused by various factors including dysfunction of bone marrow MSCs. Transplantation of MSCs is valuable in regenerative medicine for the treatment of osteonecrosis of the femoral head, osteoporosis, osteogenesis imperfecta, and other skeletal disorders. However, the mechanism of inducing MSCs to differentiate toward the osteogenic lineage is the key to an efficient treatment. Thus, a better understanding of the molecular mechanisms behind the imbalance between GR-mediated osteoblastogenesis and adipogenesis of MSCs would not only help us to identify the pathogenic causes of glucocorticoid-induced osteonecrosis and osteoporosis but also promote future clinical applications for stem cell-based tissue engineering and regenerative medicine. Here, we primarily review the signaling mechanisms involved in adipogenesis and osteogenesis mediated by GR and discuss the factors that control the adipo-osteogenic balance.

中文翻译：

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糖皮质激素受体介导的间充质干细胞成骨细胞生成与脂肪生成之间平衡的转变。

间充质干细胞（MSC）是能够分化为几种组织（例如骨骼，软骨和脂肪）的多能细胞。糖皮质激素影响多种生物学过程，例如各种细胞类型（包括成骨细胞，脂肪细胞或软骨细胞）的增殖，分化和凋亡。糖皮质激素通过结合糖皮质激素受体（GR）发挥其功能。糖皮质激素的生理浓度刺激成骨细胞增殖并促进MSC的成骨分化。然而，药理浓度的糖皮质激素不仅可以诱导成骨细胞和骨细胞凋亡，而且可以减少增殖并抑制骨祖细胞的分化。几种信号传导途径，包括Wnt，TGFβ/ BMP超家族和Notch信号传导途径，转录因子，转录后调控因子和其他调控因子调控GR介导的MSC的成骨和脂肪形成。这些信号通路靶向关键转录因子，例如Runx2和TAZ用于成骨，PPARγ和C / EBP用于脂肪形成。糖皮质激素诱导的骨坏死和骨质疏松症是由多种因素引起的，包括骨髓MSC的功能障碍。MSC的移植在再生医学中对治疗股骨头坏死，骨质疏松，成骨不全症和其他骨骼疾病具有重要价值。然而，诱导MSC向成骨细胞系分化的机制是有效治疗的关键。因此，对GR介导的成骨细胞生成和MSC脂肪生成之间不平衡背后的分子机制的更好理解，不仅有助于我们确定糖皮质激素诱导的骨坏死和骨质疏松的病因，而且还促进了基于干细胞的组织工程的未来临床应用。再生医学。在这里，我们主要审查由GR介导的脂肪形成和成骨过程涉及的信号传导机制，并讨论控制脂肪成骨平衡的因素。