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.
Department of Histopathology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK.
T J
TJ
Chambers
S
S
Fox
C J
CJ
Jagger
J M
JM
Lean
J W
JW
Chow
D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D010003:Osteoarthritis / Q000209:etiology / Q000503:physiopathology; D010812:Physical Stimulation; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D013314:Stress, Mechanical
D011453:Prostaglandins; D009569:Nitric Oxide