Structural characterization and stimulating effect on osteoblast differentiation of a purified heteropolysaccharide isolated from Hedysarum polybotrys

Zhao, Lianggong; Zhao, Hui; Sheng, Xiaoyun; Tongqiang, Chen; Dang, Zilong; An, Lihui; Ma, Jun; Feng, Shilan; Xia, Yayi

doi:10.1016/j.carbpol.2014.05.001

Cited by 18 publications

(6 citation statements)

References 37 publications

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“…Astragali Radix and Hedysari Radix have been shown to inhibit bone resorption, stimulate bone formation, and prevent ovariectomy induced osteoporosis (Wegiel and Persson, ; Choi et al, ; Zhao et al, ). Calycosin (C 16 H 12 O 5 ; Figure ) is the pharmacologically active flavonoid component of Astragali Radix and Hedysari Radix (Zhang et al, ; Cai et al, ).…”

Section: Introductionmentioning

confidence: 99%

Calycosin stimulates the osteogenic differentiation of rat calvarial osteoblasts by activating the IGF1R/PI3K/Akt signaling pathway

Fang

Xue

Zhao

et al. 2019

Cell Biology International

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Calycosin has been reported to have a strong osteogenic activity and a positive correlation with anti‐osteoporosis effects. However, its precise mechanism of action remains unclear. Since insulin‐like growth factor 1 receptor (IGF1R) signaling and phosphatidylinositol 3‐kinase/Akt (PI3K/Akt) signaling have been shown to play a pivotal role in regulating osteogenesis, we hypothesized that the osteogenic activity of calycosin is mediated by these signaling pathways. Rat calvarial osteoblasts (ROBs) were cultured in osteogenic medium containing calycosin with or without GSK1904529A (GSK) or LY294002 (LY) (inhibitors of IGF1R and PI3K, respectively). The effects on cell proliferation, alkaline phosphatase (ALP) activity, calcified nodules, mRNA or protein expression of osteogenic genes [alkaline phosphatase (Alpl), collagen type I (Col1a1), runt‐related transcription factor 2 (Runx2), Osterix, and bone morphogenetic protein 2 (Bmp2)], and phosphorylation of IGF1R and Akt were examined. The present results showed that calycosin enhanced cell proliferation, ALP activity and Alizarin Red‐S staining in a dose‐dependent manner in the range of 10−8–10−6 M, while an inhibitory effect was observed at 10−5 M. Treatment at the optimal concentration (10−6 M, a physiologically achievable concentration) increased mRNA levels of osteogenic genes and phosphorylation of IGF1R and Akt. Furthermore, treatment with GSK or LY partly reversed the effects of calycosin on ROBs, as indicated by the decreases in calycosin‐induced ALP activity, calcified nodules and osteogenic gene expression. These results suggest that the osteogenic effect of calycosin partly involves the IGF1R/PI3K/Akt signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Calycosin stimulates the osteogenic differentiation of rat calvarial osteoblasts by activating the IGF1R/PI3K/Akt signaling pathway

Fang

Xue

Zhao

et al. 2019

Cell Biology International

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“…Applying these criteria, we identified five potential suppressors (Table 1 , Supplementary Table S3 ) and 60 potential activators (Table 2 , Supplementary Table S3 ) of osteoblast differentiation. Interestingly, our screen was able to identify some known regulators for osteoblast differentiation, such as hepatocyte growth factor (Hgf) 39 , homocysteine-inducible endoplasmic reticulum stress-inducible ubiquitin-like domain member 1 (Herpud1) 40 , interferon activated gene 204 (Ifi204) 41 , and HPS3 biogenesis of lysosomal organelles complex 2 subunit 1 (Hps3) 42 . Additionally, we identified several genes with an unknown role in osteoblastogenesis, thus, opening new avenues of investigation in regulating osteoblast differentiation.…”

Section: Resultsmentioning

confidence: 99%

Cell-based RNAi screening and high-content analysis in primary calvarian osteoblasts applied to identification of osteoblast differentiation regulators

Ahmad

Kroll

Jakob

et al. 2018

Sci Rep

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Osteoblasts are responsible for the maintenance of bone homeostasis. Deregulation of their differentiation is etiologically linked to several bone disorders, making this process an important target for therapeutic intervention. Systemic identification of osteoblast regulators has been hampered by the unavailability of physiologically relevant in vitro systems suitable for efficient RNAi and for differentiation read-outs compatible with fluorescent microscopy-based high-content analysis (HCA). Here, we report a new method for identification of osteoblast differentiation regulators by combining siRNA transfection in physiologically relevant cells with high-throughput screening (HTS). Primary mouse calvarial osteoblasts were seeded in 384-well format and reverse transfected with siRNAs and their cell number and differentiation was assayed by HCA. Automated image acquisition allowed high-throughput analyses and classification of single cell features. The physiological relevance, reproducibility, and sensitivity of the method were validated using known regulators of osteoblast differentiation. The application of HCA to siRNAs against expression of 320 genes led to the identification of five potential suppressors and 60 activators of early osteoblast differentiation. The described method and the associated analysis pipeline are not restricted to RNAi-based screening, but can be adapted to large-scale drug HTS or to small-scale targeted experiments, to identify new critical factors important for early osteoblastogenesis.

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“…Arabinofuranose has been reported to be a component of polysaccharides that undergo activation during internal secretion ( Zhou et al, 2007 ), osteogenesis ( Zhao et al, 2014 ), and digestion ( Golovchenko et al, 2012 ). Additionally, arabinofuranose may be a suitable carrier for drug delivery to hepatocytes ( Groman et al, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic evaluation of irinotecan-induced intestinal mucositis based on metabolomics analysis

Zhang²,

Zhao³

et al. 2022

Front. Pharmacol.

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Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side effect of chemotherapy, especially in regimens containing irinotecan . Several studies on the pathologic mechanisms of CIM focused on both the genomics and molecular pathways triggered by chemotherapy. However, systematic evaluation of metabolomic analysis in irinotecan-induced intestinal mucositis (IIM) has not been investigated. This study aimed to comprehensively analyze metabolite changes in main tissues of IIM mouse models. Male ICR mice were assigned to two groups: the model group (n = 11) treated with CPT-11 (20 mg/kg daily; i.p.) and the control group (n= 11) with solvent for 9 days. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the metabolic alterations in the serum, intestinal, colonic, hepatic, and splenic samples of mice between two groups by multivariate statistical analyses, including GC-MS data processing, pattern recognition analysis, and pathway analysis. Forty-six metabolites, including hydrocarbons, amino acids, lipids, benzenoids, hydroxy acids, and amines, had significant changes in levels in tissues and sera of IIM mouse models. The most important pathways related to the identified metabolites were the glycerolipid metabolism in the colon and aminoacyl-tRNA biosynthesis; glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism in the liver. Our study firstly provided a comprehensive and systematic view of metabolic alterations of IIM using GC-MS analysis. The characterizations of metabolic changes could offer profound and theoretical insight into exploring new biomarkers for diagnosis and treatment of IIM.

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Structural characterization and stimulating effect on osteoblast differentiation of a purified heteropolysaccharide isolated from Hedysarum polybotrys

Cited by 18 publications

References 37 publications

Calycosin stimulates the osteogenic differentiation of rat calvarial osteoblasts by activating the IGF1R/PI3K/Akt signaling pathway

Calycosin stimulates the osteogenic differentiation of rat calvarial osteoblasts by activating the IGF1R/PI3K/Akt signaling pathway

Cell-based RNAi screening and high-content analysis in primary calvarian osteoblasts applied to identification of osteoblast differentiation regulators

Systematic evaluation of irinotecan-induced intestinal mucositis based on metabolomics analysis

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