このエントリーをはてなブックマークに追加
ID 20100
file
creator
Yoshida, Eri
Tsutsumi, Shinichi
Kuruta, Yoshihiro
Kato, Yukio
subject
PTH
PTHrP
RA
Ihh
chondrocyte
growth plate
abstract
Indian hedgehog (Ihh) is highly expressed in prehypertrophic chondrocytes in vivo and has been proposed to regulate the proliferation and maturation of chondrocytes and bone collar formation in the growth plate. In high-density cultures of rabbit growth-plate chondrocytes, Ihh mRNA was also expressed at the highest level in the prehypertrophic stage. To explore endogenous factors that regulate Ihh expression in chondrocytes, we examined the effects of various growth factors on Ihh mRNA expression in this system. Retinoic acid (RA) and bone morphogenetic protein-2 enhanced Ihh mRNA expression, whereas PTH/PTH-related peptide (PTHrP) markedly suppressed Ihh expression. RA at more than 10-8 M induced the expression of Ihh and Patched 1 (Ptc1) within 3 h, before it increased the type X collagen mRNA level at 6–24 h. Cycloheximide blocked the up-regulation of Ihh by RA, indicating the requirement of de novo protein synthesis for this stimulation. These findings suggest that RA is involved in the up-regulation of Ihh during endochondral bone formation. In contrast to RA, PTH (1–84) at 10-7 M abolished the mRNA expression of Ihh and Ptc1 within 2–4 h, before it suppressed the expression of type X collagen at 12–24 h. The inhibition of Ihh expression by PTH (1–84) did not require de novo protein synthesis. PTH (1–34), PTHrP (1–34), and (Bu)2cAMP also suppressed Ihh expression. On the other hand, Ihh has been reported to induce PTHrP synthesis in the perichondrium. Consequently, the direct inhibitory action of PTH/PTHrP on Ihh appears to be a negative feedback mechanism that prevents excess PTHrP accumulation in cartilage.
journal title
Experimental Cell Research
volume
Volume 265
issue
Issue 1
start page
64
end page
72
date of issued
2001-04-15
publisher
Elsevier
issn
0014-4827
ncid
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2001 Academic Press.
relation url
department
Graduate School of Biomedical Science