Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation.
We recently developed an experimental model whereby a single 10-min episode of mechanical stimulation induces bone formation in the eighth caudal vertebra of 13-wk-old rats. We used this model to relate the kinetics of the bone-forming response, as measured by administration of fluorescent markers, to an in situ hybridization analysis of changes in mRNA for two matrix proteins (type I collagen and osteocalcin) and a growth factor implicated in the regulation of bone formation [insulin-like growth factor I (IGF-I). We found that increased fluorochrome labeling was accompanied by an increase in the proportion of trabecular bone surfaces on which transcripts for collagen type I and osteocalcin were detectable, from < 3 to 25% 72 h after loading. IGF-I expression on trabecular surfaces showed a slightly earlier increase. We also noted intense hybridization for IGF-I in osteocytes in the diaphyseal cortex and in metaphyseal trabeculae. This was observed only in loaded bones, within 6 h of loading, and became undetectable in trabecular osteocytes 48 h and cortical osteocytes 120 h after loading. This is the first identification of a specific mRNA species in osteocytes after mechanical stimulation. Its production before the increase in transcription of matrix protein mRNA, and before the transcription of IGF-I mRNA in bone surface cells, represents persuasive evidence for a role for osteocytes, and for IGF-I, in the osteogenic response of bone to mechanical stimulation.
Lean
J M
JM
Department Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Jagger
C J
CJ
Chambers
T J
TJ
Chow
J W
JW
D000818:Animals; D003094:Collagen / Q000235:genetics; D005260:Female; D005456:Fluorescent Dyes; D015870:Gene Expression; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015675:Osteocalcin / Q000235:genetics; D010011:Osteocytes / Q000378:metabolism*; D010012:Osteogenesis; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005456:Fluorescent Dyes; D012333:RNA, Messenger; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D003094:Collagen