It has been known for more than a century that bone tissue adapts to f
unctional stress by changes in structure and mass, However, the mechan
ism by which stress is translated into cellular activities of bone for
mation and resorption is unknown, We studied the response of isolated
osteocytes derived from embryonic chicken calvariae to intermittent hy
drostatic compression as well as pulsating fluid flow, and compared th
eir response to osteoblasts and periosteal fibroblasts. Osteocytes, bu
t not osteoblasts or periosteal fibroblasts, reacted to 1 h pulsating
fluid flow with a sustained release of prostaglandin E(2). Intermitten
t hydrostatic compression stimulated prostaglandin production to a les
ser extent: after 6 and 24 h in osteocytes and after 6 h in osteoblast
s. These data provide evidence that osteocytes are the most mechanosen
sitive cells in bone involved in the transduction of mechanical stress
into a biological response. The results support the hypothesis that s
tress on bone causes fluid flow in the lacunar-canalicular system, whi
ch stimulates the osteocytes to produce factors that regulate bone met
abolism.