Osteocytic expression of mrna for c-fos and igf-i: an immediate
-early gene response to an osteogenic stimulus.
Lean, Jenny M, Alan G Mackay, Jade Wm Chow, and Timothy J Chambers.
Department of Histopathology, St George's Hospital Medical School,
London SW17 ORE, UK
APStracts 3:0031E, 1996.
We analysed 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 proto
-oncogene whose disordered regulation specifically affects bone. Both
genes were strongly expressed in osteocytes of mechanically
stimulated but not control bones, within 30 mins of the osteogenic
stimulus. IGF-I mRNA expression increased up to 6 hrs, 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 hrs, 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 signalling pathways are activated in
osteocytes during this process.
Received 18 October 1995; accepted in final form 17 January 1996.
APS Manuscript Number E501-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96