Modulation of gene expression in human osteoblasts by targeting a distal promoter region of human estrogen receptor-alpha gene

in Journal of Endocrinology
Authors:
E Lambertini
Search for other papers by E Lambertini in
Current site
Google Scholar
PubMed Close
,
L Penolazzi
Search for other papers by L Penolazzi in
Current site
Google Scholar
PubMed Close
,
V Sollazzo
Search for other papers by V Sollazzo in
Current site
Google Scholar
PubMed Close
,
F Pezzetti
Search for other papers by F Pezzetti in
Current site
Google Scholar
PubMed Close
,
M de Mattei
Search for other papers by M de Mattei in
Current site
Google Scholar
PubMed Close
,
L del Senno
Search for other papers by L del Senno in
Current site
Google Scholar
PubMed Close
,
GC Traina
Search for other papers by GC Traina in
Current site
Google Scholar
PubMed Close
, and
R Piva
Search for other papers by R Piva in
Current site
Google Scholar
PubMed Close
DOI:
https://doi.org/10.1677/joe.0.1720683
Volume/Issue:
Volume 172: Issue 3
Article Type:
Other
Page Range:
683–693
Online Publication Date:
01 Mar 2002
Free access

Sign up for journal news

Estrogen receptor (ER) alpha is expressed during osteoblast differentiation; however, both its functional role in bone metabolism and its involvement in osteoporotic pathogenesis caused by estrogen deficiency are not well understood. Loss of ER alpha gene expression could be one of the mechanisms leading to osteoporosis. Therefore, we investigated a possible modulation of ER alpha gene expression in a human osteoblastic cell line and in four primary osteoblast cultures by using a decoy strategy. Double stranded DNA molecules, mimicking a regulatory region of the ER alpha gene promoter (DNA-102) and acting as a 'silencer' in breast cancer cells, were introduced into osteoblasts as 'decoy' cis-elements to bind and functionally inactivate a putative negative transcription factor, and thus to induce ER alpha gene expression. We found that the DNA-102 molecule was able to specifically bind osteoblast nuclear proteins. Before decoy treatment, absence or variable low levels of ER alpha RNAs in the different cultures were detected. When the cells were transfected with the DNA-102 decoy, an increase in expression of ER alpha and osteoblastic markers, such as osteopontin, was observed, indicating a more differentiated osteoblastic phenotype both in the cell line and in primary cultures. These results showed that the DNA-102 sequence competes with endogenous specific negative transcription factors that may be critical for a decrease in or lack of ER alpha gene transcription. Therefore, osteoblastic transfection with the DNA-102 decoy molecule may be considered a tempting model in a putative therapeutic approach for those pathologies, such as osteoporosis, in which the decrease or loss of ER alpha expression plays a critical role in bone function.

Journal of Endocrinology is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 467 180 49
PDF Downloads 347 94 13

 

  • Collapse
  • Expand
Print ISSN:
0022-0795
Online ISSN:
1479-6805
Page(s):
11
Article Type:
Other
Print Publication Date:
01 Mar 2002
Online Publication Date:
01 Mar 2002