Prostaglandin D<inf>2</inf>pathway and peroxisome proliferator-activated receptor γ-1 expression are induced by mechanical loading in an osteoblastic cell line

• Main Authors: Chitpol Siddhivarn, Albert Banes, Catherine Champagne, Estelle L. Riché, Woranut Weerapradist, Steven Offenbacher
• Other Authors: University of North Carolina School of Dentistry
• Format: Article
• Published: 2018
• Subjects: Dentistry
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/23213
• Institution: Mahidol University

Objective: The hypothesis underlying the current study was that the arachidonic acid cascade, specifically activation of the prostaglandin (PG) D2pathway in osteoblasts, is an anabolic signal induced by mechanical loading. Background: Previous studies have shown that mechanical loading of osteoblasts triggers cyclooxygenase (COX)-2, PGE2and prostacyclin (PGI2) synthesis. Since modest mechanical loading of osteoblasts promotes bone formation, we sought to determine whether mechanical stress activates the osteoblastic PGD2pathway resulting in the synthesis of osteogenic cyclopentenones, including δ12PGJ2. 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 with14C 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, PGD2synthase 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 PGE2, PGD2and the PGD2metabolite δ12PGJ2. Mechanical strain resulted in the induction of bone nodules. Conclusions: This report indicates that mechanical loading of osteoblasts results in activation of PGD2and the concomitant expression of transcription factor PPARγ-1 mRNA. The coordinated synthesis of δ12PGJ2, 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 δ12PGJ2-PPAR pathway. © Blackwell Munksgaard 2006.