Nakamura T, Aikawa T, Iwamoto-Enomoto M, Iwamoto M, Higuchi Y, Pacifici M, Kinto N, Yamaguchi A, Noji S, Kurisu K, Matsuya T
The First Department of Oral and Maxillofacial Surgery, Osaka University Faculty of Dentistry, Suita Osaka, 565, Japan.
Biochem Biophys Res Commun. 1997 Aug 18;237(2):465-9. doi: 10.1006/bbrc.1997.7156.
In this study we asked whether members of the hedgehog gene family are involved in osteogenesis. C3H10T1/2 cells and MC3T3-E1 cells expressed the putative hedgehog receptor patched (Ptc) gene. Medium conditioned by chicken embryo fibroblast cultures expressing either Indian hedgehog or Sonic hedgehog stimulated alkaline phosphatase (APase) activity in cultures of the mouse mesenchymal cell line C3H10T1/2 and the osteoblastic cell line MC3T3-E1. These stimulatory effects were synergistically enhanced by bone morphogenetic protein-2 (BMP-2). Treatment with the amino-terminal portion of recombinant Sonic hedgehog proteins (rShh-N) up-regulated the expression of the Ptc gene within 12 h and increased production of APase in C3H10T1/2. rShh-N and BMP-2 also synergistically stimulated APase activity. rShh-N treatment did not affect the expression levels of Bmp-2, -4, -5, -6 and -7 genes. These findings indicate that hedgehog proteins directly act on osteogenic precursor cells and osteoblasts and stimulate osteogenic differentiation of these cells in co-operation with BMPs.
在本研究中，我们探讨了刺猬基因家族成员是否参与骨生成。C3H10T1/2细胞和MC3T3-E1细胞表达假定的刺猬受体patched（Ptc）基因。由表达印度刺猬或音猬因子的鸡胚成纤维细胞培养物条件化的培养基刺激了小鼠间充质细胞系C3H10T1/2和成骨细胞系MC3T3-E1培养物中的碱性磷酸酶（APase）活性。这些刺激作用被骨形态发生蛋白-2（BMP-2）协同增强。用重组音猬因子蛋白（rShh-N）的氨基末端部分处理在12小时内上调了C3H10T1/2中Ptc基因的表达，并增加了APase的产生。rShh-N和BMP-2也协同刺激了APase活性。rShh-N处理不影响Bmp-2、-4、-5、-6和-7基因的表达水平。这些发现表明，刺猬蛋白直接作用于成骨前体细胞和成骨细胞，并与BMP协同刺激这些细胞的成骨分化。
