Flavonoids of Herba Epimedii stimulate osteogenic differentiation and suppress adipogenic differentiation of primary mesenchymal stem cells via estrogen receptor pathway

Zhang, Dawei; Liu, Li; Jia, Zhenquan; Yao, Xin‐Sheng

doi:10.3109/13880209.2015.1079224

Cited by 24 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study revealed MIAT was an estrogen-inducible lncRNA and its expression was positively related to estrogen receptor (Li et al, 2018b). There was accumulating evidence to reveal that exposure of bone marrow stem cells to icariin or flavonoids of Herba Epimedii inhibited adipogenic differentiation, exhibiting decreased adipocyte numbers and downregulated mRNA expression of adipogenic differentiation markers, peroxisome proliferator‑activated receptor gamma (PPARγ) and CCAAT/enhancer‑binding protein α (C/EBPα) (Li et al, 2018c; Zhang et al, 2015); while treatment of bone marrow stem cells with estrogen receptor antagonist ICI182780 revered the effects of Herba Epimedii ingredient and promoted adipogenesis (Li et al, 2018c; Zhang et al, 2015). The study of Ihunnah et al (2014) also demonstrated activation of estrogen receptor in ASCs inhibited adipogenesis by decreasing the recruitment of the adipogenic PPARγ onto its target gene promoters, whereas the use of estrogen receptor antagonism ICI 182780 or knockdown of estrogen receptor-α via lentiviral shRNA enhanced adipogenesis by increasing the expression of PPARγ.…”

Section: Discussionmentioning

confidence: 99%

Crucial lncRNAs associated with adipocyte differentiation from human adipose-derived stem cells based on co-expression and ceRNA network analyses

Chen

Xie

Jin

2019

PeerJ

View full text Add to dashboard Cite

Background Injection of adipose-derived stem cells (ASCs) is a promising treatment for facial contour deformities. However, its treatment mechanisms remain largely unknown. The study aimed to explain the molecular mechanisms of adipogenic differentiation from ASCs based on the roles of long noncoding RNAs (lncRNAs). Methods Datasets of mRNA–lncRNA (GSE113253) and miRNA (GSE72429) expression profiling were collected from Gene Expression Omnibus database. The differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) between undifferentiated and adipocyte differentiated human ASCs were identified using the Linear Models for Microarray Data method. DELs related co-expression and competing endogenous RNA (ceRNA) networks were constructed. Protein–protein interaction (PPI) analysis was performed to screen crucial target genes. Results A total of 748 DEGs, 17 DELs and 51 DEMs were identified. A total of 13 DELs and 279 DEGs with Pearson correlation coefficients > 0.9 and p-value < 0.01 were selected to construct the co-expression network. A total of 151 interaction pairs among 112 nodes (10 DEMs; eight DELs; 94 DEGs) were obtained to construct the ceRNA network. By comparing the lncRNAs and mRNAs in two networks, five lncRNAs (SNHG9, LINC02202, UBAC2-AS1, PTCSC3 and myocardial infarction associated transcript (MIAT)) and 32 genes (i.e., such as phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), protein tyrosine phosphatase receptor type B (PTPRB)) were found to be shared. PPI analysis demonstrated PIK3R1 , forkhead box O1 (FOXO1; a transcription factor) and estrogen receptor 1 (ESR1) were hub genes, which could be regulated by the miRNAs that interacted with the above five lncRNAs, such as LINC02202-miR-136-5p-PIK3R1, LINC02202-miR-381-3p-FOXO1 and MIAT-miR-18a-5p-ESR1. LINC02202 also could directly co-express with PIK3R1. Furthermore, PTPRB was predicted to be modulated by co-expression with LINC01119. Conclusion MIAT, LINC02202 and LINC01119 may be potentially important, new lncRNAs associated with adipogenic differentiation of ASCs. They may be involved in adipogenesis by acting as a ceRNA or co-expressing with their targets.

show abstract

Section: Discussionmentioning

confidence: 99%

Crucial lncRNAs associated with adipocyte differentiation from human adipose-derived stem cells based on co-expression and ceRNA network analyses

Chen

Xie

Jin

2019

PeerJ

View full text Add to dashboard Cite

show abstract

“…For instance, Herba epimedii flavonoids improve bone health by mediating the effects of RUNX2 on osteogenesis, strongly suggesting that it could be a novel agent for treating osteoporosis. 39 Similarly, Drynaria fortune can improve the proliferation and osteogenic differentiation of stem cells in the dental pulp in a dose-dependent manner. 40 At the same time, Icariin is a flavonoid with potent effects on bone marrow MSCs’ activity.…”

Section: Discussionmentioning

confidence: 99%

Rutin promotes osteogenic differentiation of periodontal ligament stem cells through the GPR30-mediated PI3K/AKT/mTOR signaling pathway

Zhao

Xiong

Zhang

et al. 2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Rutin is one of the flavonoids found in fruits and vegetables. Recent reports have revealed that rutin is a major player in proliferation and bone development. However, data on how rutin regulates the proliferation of periodontal ligament stem cells (PDLSCs), as well as the differentiation of osteogenic cells are scanty. Here, our findings showed that rutin enhanced PDLSCs proliferation, increased ALP activity, and matrix mineralization. Moreover, rutin significantly promoted the expression of osteogenic genes and elevated phosphorylated AKT and mTOR. Treatment with LY294002 reversed these effects by inhibiting PI3K. We also found that the expression levels of GPR30 were increased by rutin. Interestingly, this upregulation was not altered after the addition of LY294002. In addition, G15, a selective antagonist of GPR30, could reduce the beneficial effects induced by rutin and interfere with the modulation of PI3K/AKT/mTOR signal transduction. Collectively, our findings revealed that rutin increased proliferation and osteogenic differentiation of PDLSCs through GPR30-mediated PI3K/AKT/mTOR signal transduction. Therefore, it could be deduced that rutin as a certain flavonoid possesses therapeutic value for periodontal bone regeneration and tissue engineering. Impact statement In our study, the effects and mechanisms of rutin on the osteogenic differentiation and proliferation of PDLSCs were investigated. Our findings might provide basic knowledge and guidance to understand and use rutin in the bioengineering of the periodontal tissues and regeneration of bones. The following is a short description of the main findings: rutin promotes the osteogenic differentiation and proliferation of PDLSCs; PI3K/AKT/mTOR signal pathway mediates the effects of rutin on PDLSCs; rutin activates PI3K/AKT/mTOR signal pathway via GPR30.

show abstract

“…MSCs were identified by flow cytometry and differentiation capability and maintained in the culture medium at 37°C. Sodium fluoride (NaF) and 17 β -estradiol (ES) served as positive control for different experiments, and PBS was used as vehicle control [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Icariin and Icariside II Reciprocally Stimulate Osteogenesis and Inhibit Adipogenesis of Multipotential Stromal Cells through ERK Signaling

Zhang

Zhao

Wan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

Self Cite

View full text Add to dashboard Cite

Herba Epimedii is a famous Chinese herbal medicine for treating bone diseases. Icariin and icariside II, the main chemical constituents, have attracted great attention from scientists for their potential as antiosteoporosis agents. Our study aimed to evaluate their effects on the lineage commitment of multipotential stromal cells (MSCs). The osteogenesis and adipogenesis of MSCs were assessed by ALP activity, calcium deposition, and adipocyte formation. The expression profiles and levels of osteogenic and adipogenic specific genes were evaluated by cDNA microarray and quantitative real-time PCR. The involvement of extracellular signal-regulated kinase (ERK) signaling was studied by enzyme-linked immunosorbent assay. Icariin and icariside II significantly increased ALP activity and mineralization during osteogenic differentiation of MSCs. Runx2, Col1, and Bmp2 were upregulated in the presence of icariin and icariside II. Meanwhile, they downregulated Pparg, Adipsin, and Cebpb expression during adipogenic differentiation. cDNA microarray revealed 57 differentially expressed genes during lineage commitment of MSCs. In addition, icariin and icariside II enhanced the phosphorylation of ERK, and the above biological effects were blocked by ERK inhibitor U0126. Icariin and icariside II may drive the final lineage commitment of MSCs towards osteogenesis and inhibit adipogenesis through the ERK signaling pathway. Both of them exert multiple osteoprotective effects and deserve more attention for their medicinal and healthcare prospects.

show abstract

Flavonoids of Herba Epimedii stimulate osteogenic differentiation and suppress adipogenic differentiation of primary mesenchymal stem cells via estrogen receptor pathway

Cited by 24 publications

References 27 publications

Crucial lncRNAs associated with adipocyte differentiation from human adipose-derived stem cells based on co-expression and ceRNA network analyses

Crucial lncRNAs associated with adipocyte differentiation from human adipose-derived stem cells based on co-expression and ceRNA network analyses

Rutin promotes osteogenic differentiation of periodontal ligament stem cells through the GPR30-mediated PI3K/AKT/mTOR signaling pathway

Icariin and Icariside II Reciprocally Stimulate Osteogenesis and Inhibit Adipogenesis of Multipotential Stromal Cells through ERK Signaling

Contact Info

Product

Resources

About