Mechanical loading stimulates bone formation by prostanoid-mediated mechanism

แรงกลกระตุ้นการสร้างกระดูกโดยผ่านกลไกการทำงานของสารพรอสทานอยด์

Name: Chitpol Siddhivarn

MeSH: Osteoblasts

MeSH: Bone Regeneration

MeSH: Cell Culture Techniques

MeSH: Cell Culture Techniques

MeSH: Gene Expression

Abstract: The purpose of this research study was to investigate PGJ2 metabolites as arachidonic acid metabolites and gene expression in response to mechanical load and clotting stimuli in osteoblastic cell line (MC3T3-E1). The effect of clotting stimuli on bone cells was determined by stimulating cells with 10 U/ml of α- thrombin. The effect of mechanical load on bone cells was determined by stretching cells with a Flexcell Strain Unit. COX-inhibitors and exogenous PGJ2 were used to examine the role of cyclopentenone on growth factors at a transcriptional level. Cells and cell media were collected from 15 seconds to 72 hours. Levels of mRNA of genes of interest were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). PGJ2 metabolites were identified by reverse-phase high performance liquid chromatography (RP-HPLC). cDNA microarrays were used to examine the pattern of gene expression. Statistical analysis used was unpaired Student’s t-test. Results revealed that thrombin enhanced the increase in prostacyclin (PGI2) secretion significantly (p<0.05). Thrombin also stimulated the expression of cyclooxygenase-2 (COX-2), platelet derived growth factor A and B mRNA levels significantly, but not BMP-2/6 and significantly down-regulated COX-1 mRNA expression level (p<0.05). Mechanical loading stimulated prostacyclin (PGI2), prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) syntheses. The levels of COXs, PDGFs, BMPs, PGD2 synthase and peroxisome proliferatoractivated receptor gamma-1 (PPARγ-1) mRNA expression were significantly increased when a 1% strain was applied to bone cells (p<0.05). Only BMP-2 and PDGF-A were significantly affected by COX-inhibitors. The up-regulated genes were involved in cell growth and differentiation and maintenance. The downregulated genes were involved in the suppression of growth and differentiation. These findings suggest that mechanical stress may play an important role in bone formation and regeneration via biochemical transduction pathways that initially involve the activation of cyclooxygenases (COXs) and subsequent cascade of growth factor synthesis

Mahidol University

Address: NAKHON PATHOM

Email: liwww@mahidol.ac.th

Name: Chitpol Siddhivarn

Role: Thesis Advisors

Created: 2009-07-09

Modified: 2552-09-09

Issued: 2009-07-09

วิทยานิพนธ์/Thesis

application/pdf

ISBN: 9740436986

CallNumber: TH C543m 2003

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degree

Descipline: Oral Biology

Grantor: Mahidol University

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