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Coculture With Endothelial Cells Enhances Osteogenic Differentiation of Periodontal Ligament Stem Cells via Cyclooxygenase‐2/Prostaglandin E 2 /Vascular Endothelial Growth Factor Signaling Under Hypoxia
Author(s) -
Zhao Lixing,
Wu Yeke,
Tan Lijun,
Xu Zhenrui,
Wang Jun,
Zhao Zhihe,
Li Xiaoyu,
Li Yu,
Yang Pu,
Tang Tian
Publication year - 2013
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2013.120548
Subject(s) - periodontal ligament stem cells , vascular endothelial growth factor , chemistry , microbiology and biotechnology , angiogenesis , hypoxia (environmental) , periodontal fiber , western blot , prostaglandin e2 , mapk/erk pathway , endocrinology , signal transduction , medicine , biology , dentistry , biochemistry , alkaline phosphatase , vegf receptors , enzyme , organic chemistry , oxygen , gene
Background: During periodontitis and orthodontic tooth movement, periodontal vasculature is severely impaired, leading to a hypoxic microenvironment of periodontal cells. However, the impact of hypoxia on periodontal cells is poorly defined. The present study investigates responses of cocultured endothelial cells (ECs) and periodontal ligament stem cells (PDLSCs) to hypoxia. Methods: Osteogenic differentiation, molecular characterization, and various behaviors of PDLSCs and human umbilical venous ECs under hypoxia were assessed by quantitative real‐time reverse‐transcription polymerase chain reaction, Western blot, and enzyme‐linked immunosorbent assay. Moreover, the effect of ECs on PDLSC osteogenic differentiation was tested using NS398 (cyclooxygenase 2 blocker), SU5416 (vascular endothelial growth factor [VEGF] receptor inhibitor), AH6809, L‐798106, and L‐161982 (EP1/2/3/4 antagonists). Results: First, hypoxia promoted osteogenic differentiation in PDLSCs and enhanced EC migration, whereas PD98059 (extracellular signal‐regulated protein kinase [ERK] inhibitor) blocked, and cocultured ECs further enhanced, hypoxia‐induced osteogenic differentiation. Second, NS398 impaired EC migration and prostaglandin E 2 (PGE 2 )/VEGF release, whereas cocultured PDLSCs and exogenous PGE 2 partially reversed it. Third, NS398 (pretreated ECs) decreased PGE 2 /VEGF concentrations. NS398‐treated ECs and AH6809/SU5416‐treated PDLSCs impaired cocultured EC–induced enhancement of PDLSC osteogenic differentiation. Conclusions: Hypoxia enhances ERK‐mediated osteogenic differentiation in PDLSCs. Coculture with EC further augments PDLSC osteogenic differentiation via cyclooxygenase‐2/PGE 2 /VEGF signaling.