Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
The aim of this study was to determine the role of the mitogen-activated protein kinase kinase (MEK) 5/extracellular signal-regulated kinase (ERK) 5 pathway in osteoblast differentiation promoted by intermittent fluid shear stress (FSS). MC3T3-E1 osteoblastic cells were subjected to 12 dyn/cm(2) intermittent FSS, and the phenotypic markers for osteoblast differentiation, such as alkaline phosphatase (ALP) activity and expression of osteopontin (OPN) and osteocalcin (OCN), were then examined. The results showed that intermittent FSS could stimulate ERK5 phosphorylation, ALP activity and the expression of OPN and OCN. When the MEK5/ERK5 pathway was selectively inhibited by BIX02189, ALP activity was suppressed, and the expression of OPN and OCN was downregulated. Intermittent FSS induce the expression of Runt-related transcription factor-2 (Runx-2), which is involved in osteoblast differentiation by promoting the transcription of the above genes. Furthermore, the expression of Runx-2 was also reduced after treatment with BIX02189. Finally, we found that intermittent FSS was a more intense stimulus than steady FSS for promoting osteoblast differentiation. In summary, our results suggest that the MEK5/ERK5 pathway mediates osteoblast differentiation promoted by intermittent FSS, which was more effective than steady FSS in the differentiation process. The MEK5/ERK5 pathway also mediates FSS-induced Runx-2 expression in osteoblast differentiation.
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Source |
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http://dx.doi.org/10.3109/03008207.2013.853755 | DOI Listing |
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