scholarly journals Forskolin and dexamethasone synergistically induce aromatase (CYP19) expression in the human osteoblastic cell line SV-HFO

2005 ◽  
Vol 152 (4) ◽  
pp. 619-624 ◽  
Author(s):  
Masatada Watanabe ◽  
Shuji Ohno ◽  
Shizuo Nakajin

Objective: Recent progress supports the importance of local estrogen secretion in human bone tissues to increase and maintain bone mineral density. In a previous study, we reported that the expression of aromatase (CYP19) is dexamethasone (Dex)-dependent and oncostatin M (OSM) increases the expression synergistically with Dex. In the present study, we examined the effects of forskolin (FSK) as another potential synergistic factor. Results: Co-administration of 100 nM Dex and 10 μM FSK increased aromatase activity 4-fold compared with Dex alone. The results of reverse transcriptase (RT)-PCR suggest that the amount of CYP19 gene transcript was also up-regulated by FSK synergistically with Dex, and that promoter I.4, which is not activated by FSK alone, is activated by FSK synergistically with Dex. The results of RT-PCR also suggest that promoter II, which responds to FSK, was not activated even in the presence of FSK in SV-HFO. The promoter I.4 sequence that was transfected into SV-HFO was activated by FSK synergistically with Dex. Conclusions: Synergistic up-regulation of aromatase activity, CYP19 gene transcript, and promoter I.4 activity were Dex-dependent and not up-regulated by FSK alone. The results of this work may form the basis of bone-specific estrogen-replacement therapy that increases the estrogen concentration in bone tissue only.

2004 ◽  
Vol 32 (2) ◽  
pp. 533-545 ◽  
Author(s):  
M Watanabe ◽  
ER Simpson ◽  
N Pathirage ◽  
S Nakajin ◽  
CD Clyne

A number of clinical studies have highlighted the importance of estrogen in bone growth and maintenance in men and postmenopausal women. In these instances, estrogen is synthesized locally within bone tissue by aromatase, encoded by the CYP19 gene. The mechanisms regulating aromatase expression in bone, however, are unclear. In this work we characterized the expression of aromatase activity and gene transcripts in the human fetal osteoblastic cell line, SV-HFO. Aromatase activity and gene transcript expression were stimulated by dexamethasone. Oncostatin M strongly stimulated aromatase expression in synergy with dexamethasone. These factors induced CYP19 transcripts that included the sequence of exon I.4 in their 5'UTR. Consistent with this, a reporter construct harboring the genomic sequence of the promoter region of exon I.4 (promoter I.4) was also activated by dexamethasone and oncostatin M. 5' deletion and mutation analysis revealed important roles for a glucocorticoid response element, an interferon gamma activating sequence and a putative binding site for Sp1. Transfection of exogenous glucocorticoid receptor, STAT3 or Sp1 increased promoter activity, indicating a potential role for these transcription factors in regulating aromatase expression in SV-HFO cells. These data suggest that the SV-HFO cell line is a valuable model with which to elucidate the mechanisms regulating local estrogen synthesis in osteoblasts.


Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 573
Author(s):  
Tereza Bělinová ◽  
Iva Machová ◽  
David Beke ◽  
Anna Fučíková ◽  
Adam Gali ◽  
...  

Ultra-small nanoparticles with sizes comparable to those of pores in the cellular membrane possess significant potential for application in the field of biomedicine. Silicon carbide ultra-small nanoparticles with varying surface termination were tested for the biological system represented by different human cells (using a human osteoblastic cell line as the reference system and a monocyte/macrophage cell line as immune cells). The three tested nanoparticle surface terminations resulted in the observation of different effects on cell metabolic activity. These effects were mostly noticeable in cases of monocytic cells, where each type of particle caused a completely different response (‘as-prepared’ particles, i.e., were highly cytotoxic, –OH terminated particles slightly increased the metabolic activity, while –NH2 terminated particles caused an almost doubled metabolic activity) after 24 h of incubation. Subsequently, the release of cytokines from such treated monocytes and their differentiation into activated cells was determined. The results revealed the potential modulation of immune cell behavior following stimulation with particular ultra-small nanoparticles, thus opening up new fields for novel silicon carbide nanoparticle biomedical applications.


2001 ◽  
Vol 26 (4) ◽  
pp. 227-233 ◽  
Author(s):  
Kousuke Iba ◽  
Hideki Chiba ◽  
Toshihiko Yamashita ◽  
Seiichi Ishii ◽  
Norimasa Sawada

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