The Effect of Δ12PGJ2 and PPARγAgonist on the Proliferation and Differentiation of Osteoblast

Abstract

Inflammatory periodontal disease is the most important cause of tooth loss in adults. Although multifactorial, the pathogenesis of periodontitis involves the presence of the plaque-retentive factors that initiates local inflammatory reaction in a predisposed host, thus provoking edema, cell influx, and release of inflammatory mediators. Among these, eicosanoids, mainly prostaglandins, seem to be important candidates in causing tissue destruction and ultimately, alveolar bone loss. Prostaglandins (PG) are 20-carbon essential fatty acids, a family of biologically active molecules and synthesized in most tissues. Early studies showed that PGs are important mediators of the inflammatory process and bone resorption, especially PGE2 is the most potent agent. PGF2 are detected in significantly high levels in inflammed gingival tissues, and up-regulate the production of the inflammatory cytokine, MMP-1. However, increased bone formation was also confirmed in animal studies by both systemic and local injection of PGE2, and it is through the divergent actions on growth and differentiation of oteoblastic cells. PGD2 is a early anti-inflammatory signal in experimental colitis, and stimulates calcification of human osteoblastic cells. PGJ2 is formed from PGD2 in vivo and PGJ2 can be rapidly converted to Δ12PGJ2 in the presence of plasma. Unlike other PGs which act through plasma membrane receptors, Δ12PGJ2 is a high affinity ligand to peroxisome proliferator-activated receptor gamma (PPARγ). PPARs are ligand-activated transcription factors belonging to the nuclear receptor family. Although adipose tissue has been recognized as a principle site of expression of PPARγ, it is expressed at lower levels in many other tissues and cell types, including cells of the monocyte/ macrophage lineage, neutrophils, T lymphocyte, and chondrocytes. Recent studies in different cell types suggest that PPAR ligands not only regulate lipid and glucose homeostasis, but may also mitigate