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

为了阐明同源盒基因Msx1和Msx2在成骨细胞和软骨细胞分化中的作用，我们分析了Msx2缺陷和Msx1， Msx2-双缺陷小鼠的骨形成。msx2缺陷小鼠颅骨骨化和颅骨孔持续存在缺陷。这种表型是由颅骨形态发生过程中成骨前沿的骨祖细胞增殖缺陷引起的，与人类顶骨孔MSX2单倍性不全非常相似。msx2缺陷小鼠在软骨内成骨方面也存在缺陷。出生后骨和软骨分化标记基因的表达缺陷表明，Msx2在成骨和软骨形成中都是必需的。我们还建立并表征了Msx1-/-， Msx2-/-, Msx1-/-；Msx2+/-, Msx1+/-；Msx2-/-和Msx1-/-；Msx2-/-细胞系均来自突变体颅骨和体壁。重组人BMP-2刺激的成骨细胞成熟在这些突变细胞系中减少。

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.