Osteocytic expression of mRNA for c-fos and IGF-I: an immediate early gene response to an osteogenic stimulus.
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.
Lean
J M
JM
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Mackay
A G
AG
Chow
J W
JW
Chambers
T J
TJ
D000818:Animals; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early; D017403:In Situ Hybridization; D007213:Indomethacin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D010011:Osteocytes / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013131:Spine / Q000502:physiology; D013314:Stress, Mechanical
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D007213:Indomethacin