Premium
Prostaglandin D 2 pathway and peroxisome proliferator‐activated receptor γ‐1 expression are induced by mechanical loading in an osteoblastic cell line
Author(s) -
Siddhivarn Chitpol,
Banes Albert,
Champagne Catherine,
Riché Estelle L.,
Weerapradist Woranut,
Offenbacher Steven
Publication year - 2006
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2005.00834.x
Subject(s) - chemistry , metabolite , osteoblast , peroxisome proliferator activated receptor , receptor , arachidonic acid , prostaglandin , medicine , prostaglandin e2 , cyclooxygenase , prostacyclin , endocrinology , enzyme , biochemistry , biology , in vitro
Objective: The hypothesis underlying the current study was that the arachidonic acid cascade, specifically activation of the prostaglandin (PG) D 2 pathway in osteoblasts, is an anabolic signal induced by mechanical loading. Background: Previous studies have shown that mechanical loading of osteoblasts triggers cyclooxygenase (COX)‐2, PGE 2 and prostacyclin (PGI 2 ) synthesis. Since modest mechanical loading of osteoblasts promotes bone formation, we sought to determine whether mechanical stress activates the osteoblastic PGD 2 pathway resulting in the synthesis of osteogenic cyclopentenones, including Δ 12 PGJ 2 . Methods: Osteoblast monolayers were stretched using a Bioflex apparatus at a frequency of 1 Hz with 1% elongation. Cells and cell media were collected at various time points: 5, 10, 15, 30 min; and 1, 4, 16, 24 h. RNA was extracted for quantitative reverse transcriptase–polymerase chain reaction (RT–PCR). In certain experiments, cells were pre‐labeled with 14 C arachidonic acid prior to stretching. Radiolabeled metabolites in cell media were identified by reverse‐phase high performance liquid chromatography (RP‐HPLC). Osteoblasts were evaluated for an induction in bone nodule formation by stretching. Results: Mechanical strain significantly increased mRNA expression of COX‐1, COX‐2, PGD 2 synthase and peroxisome proliferator‐activated receptor (PPAR) γ‐1, but not of PPARγ‐2 as compared to control unstretched cells ( p < 0.05). Mechanical loading stimulated the release of PGE 2 , PGD 2 and the PGD 2 metabolite Δ 12 PGJ 2 . Mechanical strain resulted in the induction of bone nodules. Conclusions: This report indicates that mechanical loading of osteoblasts results in activation of PGD 2 and the concomitant expression of transcription factor PPARγ‐1 mRNA. The coordinated synthesis of Δ 12 PGJ 2 , a natural ligand for PPARγ‐1, with the increased expression of PPARγ‐1, suggests that biomechanical transduction pathways that initially involve the activation of cyclooxygenases may also involve the activation of the Δ 12 PGJ 2 –PPAR pathway.