Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways

摘要: This study sought to assess the role of several signaling pathways in fluid flow shear stress-induced proliferation and differentiation normal human osteoblasts. We evaluated effects an effective dose selective inhibitors extracellular signal-regulated kinases (ERK) pathway (PD98059 U0126), nitric oxide synthase (N(omega)-nitro-L-arginine methyl ester), cyclo-oxygenase (indomethacin), or Gi/o (pertussis toxin [PTX]) on flow-mediated effects. A 30-min steady stress at 20 dynes/cm(2) increased significantly [(3)H]thymidine incorporation (an indicator proliferation), alkaline phosphatase activity index osteoblast differentiation), phosphorylation ERK, expression integrin beta1. PD98059, U0126, N(omega)-nitro-L-arginine ester completely blocked increases ERK phosphorylation, incorporation, phosphatase, but without effect beta1 expression, indicating that are essential for osteoblasts each involves activation not upregulation. Indomethacin upregulation activation, suggesting (i.e., prostacyclin and/or prostaglandin E(2)) mediates ERK-independent manner. In contrast, PTX flow-induced increase had no incorporation. only did inhibit also enhanced stimulatory activity, a PTX-sensitive may have inhibitory differentiation. summary, this shows, first time, signal transduction mechanism is complex multiple ERK-dependent independent pathways, provides circumstantial evidence there be has completing with unknown