Oscillatory flow-induced prostaglandin release involves protein kinase a and cyclooxygenase-2 in MC3T3-E1 osteoblasts

摘要

External mechanical loading of bone results in a variety of biophysical signals that may affect cellular metabolism and gene expression. Recently lacunar-canalicular fluid flow has been shown to induce a variety of physiological responses linked to bone maintenance, including increased paracrine factor release and gene transcription in vitro (1, 2). For instance, prostaglandin E2 (PGE2), an anabolic agent in vivo that stimulates bone formation, was induced by steady and pulsating fluid flow in bone cells via a mechanism involving intracellular calcium signaling (1). However, the mechanotransduction pathways of flow-induced PGE{sub}2 production in bone cells is still unclear, in particular for oscillatory flow, which occurs physiologically. Moreover the role of cyclooxygenase-2 (Cox-2), an important enzyme for PGE{sub}2 production, in flow-induced PCE{sub}2 production is uncertain. Therefore, the first goal of this study was to investigate the effects of oscillatory flow on the synthesis of PDE2 and Cox-2 mRNA levels. The second goal of the study was to elucidate the oscillatory flow-induced PGE{sub}2 signal pathway in bone cells.