Direct inhibition of Indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocyte cultures

Experimental Cell Research 265 巻 1 号 64-72 頁 2001-04-15 発行
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タイトル ( eng )
Direct inhibition of Indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocyte cultures
作成者
Yoshida Eri
Tsutsumi Shinichi
Kuruta Yoshihiro
Kato Yukio
収録物名
Experimental Cell Research
265
1
開始ページ 64
終了ページ 72
抄録
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.
著者キーワード
PTH
PTHrP
RA
Ihh
chondrocyte
growth plate
言語
英語
資源タイプ 学術雑誌論文
出版者
Elsevier
発行日 2001-04-15
権利情報
Copyright (c) 2001 Academic Press.
出版タイプ Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 0014-4827
[DOI] 10.1006/excr.2001.5161
[PMID] 11281644
[NCID] AA00641011
[DOI] http://dx.doi.org/10.1006/excr.2001.5161