Fluid Flow Induction of Cyclo-Oxygenase 2 Gene Expression in Osteoblasts Is Dependent on an Extracellular Signal-Regulated Kinase Signaling Pathway

Abstract

Mechanical loading of bone may be transmitted to osteocytes and osteoblasts via shear stresses at cell surfaces generated by the flow of interstitial fluid. The stimulated production of prostaglandins, which mediates some effects of mechanical loading on bone, is dependent on inducible cyclo-oxygenase 2 (COX-2) in bone cells. We examined the fluid shear stress (FSS) induction of COX-2 gene expression in immortalized MC3T3-E1 osteoblastic cells stably transfected with ؊371/؉70 base pairs (bp) of the COX-2 5-flanking DNA (Pluc371) and in primary osteoblasts (POBs) from calvaria of mice transgenic for Pluc371. Cells were plated on collagen-coated glass slides and subjected to steady laminar FSS in a parallel plate flow chamber.

Integrin-mediated Adhesion and Soluble Ligand Binding Stabilize COX-2 Protein Levels in Endothelial Cells by Inducing Expression and Preventing Degradation

“…at the endothelial cell luminal surface into intracellular signaling events (56,57). The induction of COX-2 by soluble integrin ligands observed in the present study is consistent with the reported induction of COX-2 expression in endothelial cells (58 -60) and osteoblasts (61,62) in response to fluid shear stress. These observations raise the possibility that vascular integrins on tumor endothelial cells may contribute to sustain COX-2 expression in response to increased shear stress due to the pathological architecture of tumor vessels (63) or to increased levels of circulating soluble ECM protein fragment observed in cancer conditions (64,65).…”

Release of nitric oxide, but not prostaglandin E2, by bone cells depends on fluid flow frequency

“…[6][7][8][9][10][11] These results have been found in osteoblastic cell lines, and in primary bone cells from several species including humans. 8,[12][13][14][15][16][17][18][19] Specifically, the production of nitric oxide (NO) and prostaglandins (PG) is stimulated in bone cells in response to fluid flow. 8,[20][21][22][23] Osteocytes are more responsive than osteoblasts, whereas periostial fibroblasts show almost no response.…”

GRK2 desensitizes flow-induced responses in osteoblasts

“…In an earlier study, we demonstrated the role of oscillatory flow in the induction of cytosol Ca 2+ release from the ER, and enhancement of mRNA expression of osteopontin (You et al, 2001). Other researchers also showed that flow stimulation on bone cells enhances cyclooxygenase-2 (COX-2) expression, causes activation of the ERK pathway, and leads to ATP release (Wadhwa et al, 2002;Genetos et al, 2007;Okumura et al, 2008). However, long-term constant mechanical loading does not increase the response of bone cells continuously.…”