study of the function of a homeobox gene family Msx in osteochondrogenesis

同源盒基因家族Msx在骨软骨形成中的功能研究

• 批准号: 11670746
• 负责人: UCHIYAMA Makoto
• 金额: $ 2.5万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670746/
• 关键词: osteoblast; Msx1; Msx2; BMP; Sox9; 軟骨細胞; BMP-2

To clarify the function of homeobox genes Msx1 and Msx2 in osteoblast and chondrocyte differentiation, we analyzed the bone formation of Msx2-deficient and Msx1, Msx2- double deficient mice. Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina. Msx2-deficient mice also have defects in endochondral ossification. Post-natal deficits in expression of marker genes for bone and catilage differentiation indicate that Msx2 is required for both osteogenesis and chondrogenesis. We also established and characterized Msx1-/-, Msx2-/-, Msx1-/- ; Msx2+/-, Msx1+/- ; Msx2-/-, and Msx1-/- ; Msx2-/- cell lines from both mutant calvaria and body wall. Osteoblastic maturation stimulated by recombinant human BMP-2 was reduced in these mutant cell lines.

为了阐明同源异型盒基因Msx 1和Msx 2在成骨细胞和软骨细胞分化中的功能，我们分析了Msx 2缺陷和Msx 1，Msx 2双缺陷小鼠的骨形成。msx 2基因缺陷小鼠存在颅骨骨化和颅骨孔持续存在的缺陷。这种表型是由于颅骨形态发生过程中成骨前沿的骨祖细胞增殖缺陷所致，与顶骨孔中人类MSX 2单倍不足相关的表型非常相似。msx 2缺陷小鼠也有软骨内骨化缺陷。骨和软骨分化标记基因表达的出生后缺陷表明，Msx 2是骨生成和软骨生成所必需的。我们还建立并表征了Msx 1-/-、Msx 2-/-、Msx 1-/-、Msx 2 +/-、Msx 1 +/-、Msx 2-/-和Msx 1-/-、Msx 2-/-细胞系。在这些突变细胞系中，重组人BMP-2刺激的成骨细胞成熟减少。

项目成果

Satokata I,Ma L, et al.: "Msx-2 deficiecy in mice causes pleiotrophic defects in bone growth and ectodermal organ formation."Nature Genetics. 24. 391-395 (2000)

Satokata I、Ma L 等人：“小鼠中的 Msx-2 缺陷会导致骨骼生长和外胚层器官形成的多效性缺陷。”《自然遗传学》。

Satokata I et al.: "Msx-2 deficiency in mice causes pleiotrophic defects in bone growth and ectodermal organ formation"Nature Genetics. (印刷中). (2000)

Satokata I 等人：“小鼠的 Msx-2 缺陷导致骨骼生长和外胚层器官形成的多效缺陷”（Nature Genetics）（2000 年出版）。

Satokata I: "Msx-2 deficiecy in mice causes pleiotrophic defects in bone growth and ectodermal organ formation."Nature Genetics. 24. 391-395 (2000)

Satokata I：“小鼠中的 Msx-2 缺陷会导致骨骼生长和外胚层器官形成的多效性缺陷。”《自然遗传学》。

Satokata I, Ma L, Oshima H, Bei M, Woo I, Nishizawa K, Maeda T, Takano Y, Uchiyama M, Heaney S, Peters H, Tang Z, Maxon R, Maas R.: "Msx-2 deficiecy in mice causes pleiotrophic defects in bone growth and ectodermal organ formation."Nature Genetics. 24. 39

Satokata I、Ma L、Oshima H、Bei M、Woo I、Nishizawa K、Maeda T、Takano Y、Uchiyama M、Heaney S、Peters H、Tang Z、Maxon R、Maas R.：“小鼠中的 Msx-2 缺陷