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Hydroxysafflor Yellow A-Induced Osteoblast Differentiation and Proliferation of BM-MSCs by Up-Regulating Nuclear Vitamin D Receptor.

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BACKGROUND Vitamin D receptor (VDR) is critical for mineral and bone homeostasis, since it plays an essential role in the osteoblast differentiation of bone marrow mesenchymal stem cells (BM-MSCs). Hydroxysafflor… Click to show full abstract

BACKGROUND Vitamin D receptor (VDR) is critical for mineral and bone homeostasis, since it plays an essential role in the osteoblast differentiation of bone marrow mesenchymal stem cells (BM-MSCs). Hydroxysafflor yellow A (HSYA) has the potential to promote bone mineralization and inhibit bone resorption, while its detailed mechanism needs to be elaborated. OBJECTIVE This review intends to explore the action of HSYA on the proliferation and differentiation of BM-MSC and the underlying mechanism. METHOD Added different concentrations of HSYA to BM-MSC, and CCK-8 and EdU were used to detect cell viability and proliferation. The alkaline phosphatase (ALP) was used to observe the differentiation ability of BM-MSC osteoblasts. The calcium uptake and mineralization of osteoblast-like cells were observed by alizarin red staining. And the level of calcium ion uptake in cells was detected by the flow cytometry. AutoDock was performed for molecular docking of HSYA to VDR protein. Immunofluorescence and western blotting were performed to detect the expression of VDR expression levels. Finally, the effect of VDR was verified by a VDR inhibitor. RESULT After treatment with HSYA, the proliferation and calcium uptake of BM-MSC was increased. The level of ALP increased significantly, and reached the peak on the 12th day. HSYA promoted calcium uptake and calcium deposition, and mineralization of osteoblasts. The western blotting and immunofluorescence showed that HSYA increased the expression of VDR in the osteoblast-like cell's nucleus, and upregulated Osteocalcin, S100 calcium-binding protein G, and CYP24A1. In addition, HYSA treatment increased the expression of osteopontin and the synthesis of osteogenic proteins such as Type 1 collagen. After the addition of the VDR inhibitor, the effect of HSYA was weakened. CONCLUSION HSYA could significantly promote the activity and proliferation of osteoblasts, and increase the expression level of VDR in osteoblasts. HSYA may also improve calcium absorption by osteoblasts through regulating the synthesis of calcium-binding protein and vitamin D metabolic pathway-related proteins.

Keywords: hsya; calcium; proliferation; expression; differentiation; vdr

Journal Title: Current molecular medicine
Year Published: 2022

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