AJP - Endocrinology and Metabolism, Vol 270, Issue 6 E937-E945, Copyright © 1996 by American Physiological Society
Osteocytic expression of mRNA for c-fos and IGF-I: an immediate early gene response to an osteogenic stimulus
J. M. Lean, A. G. Mackay, J. W. Chow and T. J. Chambers
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
We analyzed the expression, during the osteogenic response of bone to
mechanical stimulation, of insulin-like growth factor I (IGF-I), a growth
factor implicated in bone formation, and c-fos, a protooncogene in which
disordered regulation specifically affects bone. Both genes were strongly
expressed in osteocytes of mechanically stimulated but not control bones
within 30 min of the osteogenic stimulus. IGF-I mRNA expression increased
up to 6 h, was restricted to osteocytes, and was strongly suppressed by
indomethacin. Although early IGF-I mRNA expression was resistant to
cycloheximide, there was a degree of suppression after 6 h, raising the
possibility that IGF-I expression might be prolonged by autocrine
mechanisms. c-fos mRNA was increased both in osteocytes and on bone
surfaces. At both sites, c-fos expression was transient, prolonged by
cycloheximide, and was strongly stimulated even in the presence of
indomethacin. Thus osteocytes respond to mechanical stimulation with
immediate prolonged expression of IGF-I and immediate transient expression
of c-fos, implicating osteocytes in the osteogenic response to mechanical
stimulation. Moreover, the different spatial distribution and indomethacin
sensitivity of c-fos and IGF-I gene expression suggest that at least two
signaling pathways are activated in osteocytes during this process.
