Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Introduction: Odontoblasts, terminally differentiated dentin-producing cells, critically rely on lysosomal functions for intracellular recycling and renewal. Beyond their traditional degradative role, lysosomes actively orchestrate cellular responses to external stimuli through precise and rapid intracellular trafficking and positioning. This study aimed to explore the influence of lysosomal positioning on odontoblast mineralization and the underlying mechanisms implicated in carious inflammation.
Methods: Human dental pulp stem cells were induced to differentiate into human odontoblast-like cells (hOBLCs). hOBLCs were treated with various doses of LPS (0.1, 1, 5 μg/mL) to mimic carious inflammation. Lysosomal positioning was examined by immunofluorescence staining of lysosomal associated membrane protein 1 in healthy and carious human teeth, LPS-treated hOBLCs, mouse lower incisors at postnatal day 2.5, and mineralization medium cultured human dental pulp stem cells. Lysosomal positioning was manipulated by knockdown or overexpression of SNAPIN or ARL8B. Mineralization was assessed by ARS staining and expression of DSPP and DMP1. Lysosomal exocytosis was examined by detection of lysosomal-plasma membrane fusion, surface exposure of lysosomal associated membrane protein 1 luminal epitopes (1D4B), and extracellularly released lysosomal enzymes.
Results: Peripheral lysosomal positioning was markedly increased in odontoblasts within moderate and extensive carious lesions (P < .001) and in hOBLCs following LPS treatment. Increased peripheral dispersion of lysosomes was similarly observed during odontoblastic differentiation in vivo and in vitro. Moreover, peripheral lysosomal positioning promoted mineralization in inflamed hOBLCs, potentially via mTORC1 signaling pathway and lysosomal exocytosis.
Conclusion: Inflammatory stimuli prompted a relocation of lysosomes in odontoblasts, redistributing them from perinuclear location toward the cell periphery, which in turn facilitated mineralization, potentially via mTORC1 signaling and lysosomal exocytosis.
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http://dx.doi.org/10.1016/j.joen.2024.11.006 | DOI Listing |
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