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Chrysosplenetin promotes osteoblastogenesis of bone marrow stromal cells via Wnt/β-catenin pathway and enhances osteogenesis in estrogen deficiency-induced bone loss.

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机构: [1]Department of Surgery, The University of Alberta, Edmonton, Alberta,Canada [2]The National Key Discipline and the Orthopedic Laboratory,Guangzhou University of Chinese Medicine, Guangzhou, Guangdong,People’s Republic of China [3]School of Medicine, South China University ofTechnology, Guangzhou, Guangdong, People’s Republic of China [4]Department of Orthopedic, The First Affiliated Hospital of GuangzhouUniversity of Chinese Medicine, Guangzhou, Guangdong, People’s Republicof China [5]Hip Preserving Ward, The First Affiliated Hospital of GuangzhouUniversity of Chinese Medicine, No. 3 Orthopaedic Region, Guangzhou,Guangdong, People’s Republic of China.
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Chrysosplenetin is an O-methylated flavonol compound isolated from the plant Chamomilla recutita and Laggera pterodonta. The aim of our research is to evaluate the function of Chrysosplenetin on osteogenesis of human-derived bone marrow stromal cells (hBMSCs) and inhibition of estrogen deficiency-induced osteoporosis via the Wnt/β-catenin signaling pathway. hBMSCs are cultured and treated by Chrysosplenetin in the absence or presence of Wnt inhibitor dickkopf-related protein 1 (DKK1) or bone morphogenetic protein 2 (BMP2) antagonist Noggin. RT-qPCR is taken to identify the genetic expression of target genes of Wnt/β-catenin pathway and osteoblast-specific markers. The situation of β-catenin is measured by western blot and immunofluorescence staining. An ovariectomized (OVX) mouse model is set up to detect the bone loss suppression by injecting Chrysosplenetin. Micro-CT and histological assay are performed to evaluate the protection of bone matrix and osteoblast number. Serum markers related with osteogenesis are detected by ELISA. In the present study, it is found that Chrysosplenetin time-dependently promoted proliferation and osteoblastogenesis of hBMSCs reaching its maximal effects at a concentration of 10 μM. The expressions of target genes of Wnt/β-catenin pathway and osteoblast-specific marker genes are enhanced by Chrysosplenetin treatment. Furthermore, the phosphorylation of β-catenin is decreased, and nuclear translocation of β-catenin is promoted by Chrysosplenetin. Osteogenesis effects mentioned above are founded to be blocked by DKK1 or BMP2 antagonist Noggin. In vivo study reveals that Chrysosplenetin prevents estrogen deficiency-induced bone loss in OVX mice detected by Micro-CT, histological analysis, and ELISA. Our study demonstrates that Chrysosplenetin improves osteoblastogenesis of hBMSCs and osteogenesis in estrogen deficiency-induced bone loss by regulating Wnt/β-catenin pathway.

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出版当年[2018]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 3 区 细胞生物学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 细胞与组织工程 2 区 细胞生物学 2 区 医学:研究与实验
第一作者:
第一作者机构: [1]Department of Surgery, The University of Alberta, Edmonton, Alberta,Canada [2]The National Key Discipline and the Orthopedic Laboratory,Guangzhou University of Chinese Medicine, Guangzhou, Guangdong,People’s Republic of China
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通讯作者:
通讯机构: [4]Department of Orthopedic, The First Affiliated Hospital of GuangzhouUniversity of Chinese Medicine, Guangzhou, Guangdong, People’s Republicof China [5]Hip Preserving Ward, The First Affiliated Hospital of GuangzhouUniversity of Chinese Medicine, No. 3 Orthopaedic Region, Guangzhou,Guangdong, People’s Republic of China.
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