The role of prostaglandins and nitric oxide in the response of bone to mechanical forces.

We have developed an experimental model whereby bone is exposed to a brief episode of mechanical stimulation, which is followed by bone formation. The earliest response is in osteocytes, which express c-fos and insulin-like growth factor (IGF-1) within 30-60min. Thirty-six to 72h after loading bone matrix gene expression occurs on bone surfaces. The osteogenic response can be suppressed by a single dose of nitric oxide synthase (NOS) or prostaglandin (PG) synthase inhibitors, if these are administered just before mechanical stimulation: similar doses after stimulation have no effect. There is a later phase of indomethacin-sensitivity associated with COX-2 expression in bone at 6h. Thus, mechanically induced osteogenesis involves early expression of c-fos and IGF-1 by osteocytes, which are believed to be the strain-sensitive cells in bone. Both NOS and PG synthase, either in parallel or in sequence, are crucial to the initial transduction of the mechanical stimulus into an osteogenic response.