Osterix/Sp7 regulates mesenchymal stem cell mediated endochondral ossification
Osterix/Sp7 regulates mesenchymal stem cell mediated endochondral ossification
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DOI：
10.1002/jcp.21176
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发表时间：
2008-01-01
影响因子：
5.6
通讯作者：
Drissi, Hicham
中科院分区：
文献类型：
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作者：
Kaback, Lee A.;Soung, Do Y.;Drissi, Hicham
我们研究了锌指蛋白OSX在小鼠软骨内成骨过程中的表达和调控。在研究OSX在胚胎发生过程中的时空调控时，我们发现OSX在整个发育过程中都存在，但它的表达仅限于未成熟的软骨/骨祖细胞和成熟的成骨细胞，不包括肥大的软骨细胞。使用骨折模型，我们显示OSX蛋白在骨膜间充质祖细胞和骨折骨痂中嵌入的未成熟软骨细胞和成骨细胞中的表达模式一致。相比之下，肥大的软骨细胞、血管和纤维组织中没有OSX的表达。此外，使用从骨折愈合过程中分离的骨痂RNA，我们观察到OSX转录与Runx2相似，并在软骨和骨骼表型标记上存在差异重叠。此外，在肢芽来源的MLB 13MYC Clone 17细胞中，我们发现PTHrP抑制软骨细胞的成熟，而它增强了这些软骨/骨祖细胞中OSX的mRNA水平。OSX功能的得失实验表明，OSX对软骨形成和软骨细胞成熟有抑制作用，但对成骨细胞成熟有促进作用。总之，我们的发现首次证明了OSX抑制软骨细胞分化的分子机制，并进一步表明该转录因子在骨修复过程中介导软骨内成骨的作用。
We investigated the expression and regulation of the zinc finger protein Osterix (Osx) during endochondral ossification in mice. In studies to determine the temporal and spatial regulation of Osx mRNA and protein during embryogenesis we found it to be present throughout development, but its expression is restricted to the immature chondro/osteoprogenitor cells and mature osteoblasts, excluding hypertrophic chondrocytes. Using a fracture model, we show a consistent pattern of Osx protein expression in mesenchymal progenitor cells in the periosteum and immature chondrocytes and osteoblasts embedded in the fracture callus. In contrast, hypertrophic chondrocytes, vessels and fibrous tissue were devoid of Osx expression. Additionally, using RNA isolated from fracture callus throughout the healing process, we observe that Osx transcripts parallel that of Runx2 and differentially overlap both cartilage and bone phenotypic markers. Furthermore, using limb bud-derived MLB 13MYC Clone 17 cells, we show that PTHrP inhibited chondrocyte maturation while it enhanced mRNA levels of Osx in these chondro/osteoprogenitor cells. Gain and loss of function of Osx function experiments with these cells demonstrated that Osx serves as an inhibitor of chondrogenesis and chondrocyte maturation, while it promotes osteoblast maturation. Together, our findings provide the first demonstration of the molecular mechanisms underlying Osx inhibition of chondrocyte differentiation, and further suggest a role for this transcription factor in mediating endochondral ossification during bone repair.