Salidroside accelerates fracture healing through cell-autonomous and non-autonomous effects on osteoblasts

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• 作者：Xiao Qin Guo ; Lin Qi ; Jing Yang ; Yue Wang ; Chuan Wang…
• 关键词：Salidroside ; Osteoblast ; Hypoxia ; inducible factor ; 1α (HIF ; 1α) ; Vascular endothelial growth factor (VEGF) ; Fracture
• 刊名：Cell and Tissue Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：367
• 期：2
• 页码：197-211
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Human Genetics; Proteomics; Molecular Medicine;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0878
• 卷排序：367

文摘

Salidroside (SAL), a major active component of Rhodiola rosea L., exhibits diverse pharmacological effects. However, the direct roles of SAL in fracture healing remain largely unknown. Here, we demonstrate that SAL significantly promotes proliferation by altering the cell-cycle distribution of osteoblastic cells. SAL also greatly stimulates osteoblast differentiation and mineralization by inducing the expression of Runx2 and Osterix. In addition to its osteoblast-autonomous effects, SAL can activate the HIF-1α pathway coupling of angiogenesis and osteogenesis through cell-non-autonomous effects. Our in vitro results suggest that SAL significantly up-regulates HIF-1α expression at the mRNA and protein levels. Furthermore, the nuclear translocation and transcriptional activity of HIF-1α and the HIF-responsive gene VEGF increase following SAL treatment. Our mechanistic study revealed that the regulation of osteoblastic proliferation and HIF-1α expression partly involves MAPK/ERK and PI3K/Akt signaling. Our in vivo analysis also demonstrated that SAL can promote angiogenesis within the callus and accelerate fracture healing. Thus, SAL promotes skeletal regeneration in cell-autonomous and cell-non-autonomous ways and might be a potential therapy for accelerating fracture healing.