Soluble Klotho regulates bone differentiation by upregulating expression of the transcription factor EGR‐1

Toan, Nguyen Khanh; Tai, Nguyen Chi; Kim, Soo‐A; Ahn, Sang‐Gun

doi:10.1002/1873-3468.13613

Cited by 16 publications

(8 citation statements)

References 39 publications

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“…The majority of subjects in the present study had moderately or poorly differentiated tumors, with most of these same subjects also having undetectable levels of Klotho. According to the literature, the role of Klotho may be indirect, through binding to growth factors, such as FGF-23, to assist in cellular differentiation of several cell types, such as neural cells ( 89 ), adipose-derived stem cells ( 90 ), muscle stem cells ( 91 ) and bone cells ( 92 ). Therefore, the absence of Klotho in the subjects of the present study may have contributed to the lack of differentiation.…”

Section: Discussionmentioning

confidence: 99%

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

et al. 2022

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Klotho, a cellular anti-senescence protein, is related to antitumor actions, growth regulation, proliferation and invasiveness in several types of tumor, including breast cancer. The present study aimed to analyze the serum levels of αKlotho in patients with breast cancer according to histopathological and immunohistochemical variables. A total of 74 patients and 60 healthy controls were recruited. Peripheral blood samples were collected and serum levels were assessed by sandwich ELISA. Clinical and diagnostic data were obtained from medical records and databases of the Clinical Hospital of the Federal University of Uberlândia (Uberlândia, Brazil). The results indicated no difference in the levels of αKlotho between patients and controls (P=0.068); however, the number of patients with breast cancer with undetectable αKlotho was high (n=52). Thus, the variables that were associated with the lowest survival rates were analyzed, relating them to undetectable αKlotho. Among cases of metastatic tumors or tumors with poor differentiation, positive lymph node status and triple-negative status, patients with undetectable αKlotho predominated and had unfavorable overall survival. Due to the significant results obtained in triple-negative patients, an in vitro analysis was performed to determine whether estrogen receptors (ERs) have a role in αKlotho production. Treatment of MCF-7 cells with ER agonists, estradiol (E2) and diarylpropionitrile (DPN), resulted in increases in αKlotho expression and supernatant levels of both agonists, demonstrating a direct association between the ER and Klotho production; of note, the ERβ-specific agonist DPN tripled αKlotho expression when compared to E2 (P=0.078). These data suggested that undetectable αKlotho in the serum of patients with breast cancer is related to unfavorable histopathological variables and poor prognosis and ERs possibly have an important role in maintaining adequate quantities of αKlotho.

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Section: Discussionmentioning

confidence: 99%

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

et al. 2022

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“…The Egr-1 gene, as a member of the zinc finger structure transcription factor family, is located on human chromosome 5q31 and encodes a DNA-binding transcription factor of ~80 kDa (39). It has been demonstrated that Egr-1 serves an important role in cell growth, differentiation and apoptosis (16,(40)(41)(42)(43)(44). At the same time, Egr-1 is closely associated with the occurrence and development of certain diseases, for example tutor and leukemia, however the specific signaling pathway of each of them remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

Wang

Zhao

et al. 2022

Oncol Lett

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“…Overexpression of the AP-1 transcription factor JunB induces osteoblast differentiation [32]. Egr1 co-regulates osteoblast differentiation with several osteoblast-related genes, and Egr1 overexpression contributes to osteoblast differentiation [33][34]. Klf10 is a member of the Krüppel-like family of transcription factors, Klf10 upregulation effectively promotes osteoblast differentiation [35].…”

Section: Discussionmentioning

confidence: 99%

Gujin Dan is A Chinese Medicine Formulation That Stimulates Cell Proliferation And Differentiation By Controlling Multiple Genes Involved In MC3T3-E1 Cells

Zhou

Liu

Zhou

et al. 2021

Preprint

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Background: The development of Chinese medicine has been practised in China over a long period of time, and China has long used single medicines in various forms of decoction to treat illnesses, and later learned to combine several medicines to form formulas to enhance the effects of the medicines. The use of Chinese herbal medicines and formulas has played a pivotal role in the prevention and treatment of diseases in China since ancient times. The application of Chinese herbal preparations in the field of osteoporosis treatment has received widespread attention, and Gujin Dan（GJD） is one of the representative herbal formulas, however, the exact minute mechanism of its treatment of osteoporosis remains to be elucidated.Methods: In the study, we prepared an aqueous extract of GJD and measured the effect of different administration concentrations of GJD on cell proliferation by CCK-8 assay, and the effect of GJD on cell differentiation ability by Alizarin Red S Staining, Alkaline Phosphatase Staining and quantitative assay. Changes in gene expression patterns of MC3T3-E1 cells under GJD treatment were investigated by RNA-seq analysis and validation methods.Results: We demonstrate that GJD promotes the proliferation and differentiation of Mc3t3-e1 cells through the regulation of multiple functional genes. This was mainly achieved by regulating the expression levels of four categories of genes that promote the proliferation of Mc3t3-e1 cells or osteoblasts, inhibit apoptosis and autophagy, inhibit osteoclast formation and differentiation, and promote osteoblast differentiation. In addition, GJD slightly increased the expression levels of gene markers in osteoblasts. Conclusions: Our findings suggest that GJD promotes proliferation and differentiation of MC3T3-E1 cells and inhibits osteoclastogenesis and differentiation, as well as apoptosis and autophagy, through the synergistic interaction of various herbs and their active components in GJD. This study has significantly improved the current understanding of the molecular effects of GJD on MC3T3-E1 cells. This study also provides new ideas for possible strategies to further prevent and treat bone metabolism-related diseases using traditional Chinese medicinal preparations.

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Soluble Klotho regulates bone differentiation by upregulating expression of the transcription factor EGR‐1

Cited by 16 publications

References 39 publications

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

Gujin Dan is A Chinese Medicine Formulation That Stimulates Cell Proliferation And Differentiation By Controlling Multiple Genes Involved In MC3T3-E1 Cells

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