Noggin inhibits chondrogenic but not osteogenic differentiation in mesodermal stem cell line C1 and skeletal cells.
Noggin inhibits chondrogenic but not osteogenic differentiation in mesodermal stem cell line C1 and skeletal cells.
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DOI：
10.1210/en.2003-0685
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发表时间：
2004-07
期刊：
影响因子：
4.8
通讯作者：
A. Nifuji;O. Kellermann;M. Noda
中科院分区：
文献类型：
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作者：
A. Nifuji;O. Kellermann;M. Noda
成骨细胞和成软骨细胞来源于共同的间充质祖细胞。虽然骨形态发生蛋白诱导间充质分化成成骨和chodrogenic谱系细胞在体外，其抑制剂，头蛋白，表达专门在软骨形成，但不成骨分化的胚胎癌衍生的中胚层细胞系，C1。我们假设Noggin可能以谱系特异性方式调节细胞分化。为了验证这一假设，使用重组腺病毒（Ad/Noggin）在中胚层C1细胞中过表达Noggin，以检查Noggin是否特异性抑制软骨形成分化。通过重组腺病毒感染的头蛋白过表达降低了C1细胞聚集体中Sox 9、patched、Ihh和II型、X型和XI型胶原mRNA的表达水平，所述C1细胞聚集体通过在分化培养基中培养而被诱导分化成软骨细胞谱系。与此相反，Noggin过表达并不影响C1细胞的成骨分化，因为成骨细胞表型标志物如骨钙素和碱性磷酸酶mRNA水平没有改变。我们进一步研究了是否Noggin也差异影响软骨形成和成骨肢体发育中使用长骨器官培养。将Ad/Noggin感染到体外培养在滤膜上或卵内培养在绒毛尿囊膜上的孕15.5 d后的肢体骨骼雏形中，抑制软骨形成的水平，基于阿辛蓝染色进行评估。这些结果表明，头蛋白特异性地阻断中胚层干细胞系C1和骨骼细胞中的软骨分化，而不是成骨分化。
Osteoblasts and chondroblasts are derived from common mesenchymal progenitors. Although bone morphogenetic protein induces mesenchymal differentiation into both osteogenic and chodrogenic lineage cells in vitro, its inhibitor, Noggin, is expressed exclusively during chondrogenic but not osteogenic differentiation in an embryonal carcinoma-derived mesodermal cell line, C1. We hypothesized that Noggin may regulate cell differentiation in a lineage-specific manner. To test this hypothesis, Noggin was overexpressed using recombinant adenovirus (Ad/Noggin) in mesodermal C1 cells to examine whether Noggin specifically inhibits chondrogenic differentiation. Noggin overexpression by recombinant adenovirus infection reduced Sox9, patched, Ihh, and type II, X, and XI collagen mRNA expression levels in C1 cell aggregates that were induced to differentiate into chondrocyte lineage by culturing in differentiation medium. In contrast, Noggin overexpression did not affect osteogenic differentiation in C1 cells because osteoblast phenotypic markers such as osteocalcin and alkaline phosphatase mRNA levels were not altered. We further examined whether Noggin also differentially affects chondrogenesis and osteogenesis in limb development by using organ cultures of long bone. Ad/Noggin infection into 15.5 d post conception limb skeletal rudiments that were cultured on filter membrane in vitro or on the chorioallantoic membranes in ovo inhibited the levels of chondrogenesis, which were evaluated based on alcian blue staining. These results suggest that Noggin specifically blocks chondrogenic differentiation, rather than osteogenic differentiation, in mesodermal stem cell line C1 and skeletal cells.