NEL2 GENE IN BONE FORMATION AND CRANIAL SUTURE CLOSURES
NEL2 基因在骨形成和颅缝闭合中的作用
基本信息
- 批准号:2829902
- 负责人:
- 金额:$ 12.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-09-01 至 2004-08-31
- 项目状态:已结题
- 来源:
- 关键词:3T3 cells SDS polyacrylamide gel electrophoresis bone regeneration clinical research craniosynostosis developmental neurobiology epiphysis gene expression gene mutation genetic disorder human tissue in situ hybridization laboratory rat normal ossification northern blottings organ culture osteoblasts osteogenesis polymerase chain reaction skull western blottings wound healing
项目摘要
The applicant proposes to investigate the function of NEL-2, a novel gene isolated in craniosynostosis (CS), in bone formation and premature suture closure. CS, which affects roughly one of every 3,000 infants, is the premature obliteration of cranial sutures in association with cranial dysmorphism. We have isolated and identified cDNA whose expression is upregulated in the premature suture fusion sites of patients with a prevalent type of CS, non-familial unilateral coronal synostosis (UCS). The nucleotide sequence of the full length cDNA of this gene has approximately 61 percent homology with the chicken nel gene, and thus has been named this cDNA human NEL-2. Both chicken nel and human NEL-2 consist of 6 EGF-like repeats. We demonstrated that the human NEL-2 messages are primarily localized in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins and within the condensing mesenchymal cells of the newly formed bone. Human NEL-2 is specifically expressed in fetal brain but not in fetal lung, kidney or liver. We have also shown that rat NEL-2 is expressed in rat calvarial osteoprogenitor cells and is largely absent in rat tibia and fibroblast cell culture. Mammalian expression vectors expressing rat NEL-2 were constructed and transfected into MC3T3 cell line. An approximate two and a half-fold increase in mineralization was seen as compared to the control. In addition, overexpression of rat NEL-2 induced BMP-2 gene expression. Our data suggest that the NEL-2 gene is preferentially expressed in cranial intramembranous bone and neural tissue, and it may be associated with membranous bone formation. Therefore, we hypothesize that the overexpression of the NEL-2 gene product induces the overproduction of cranial membranous bone. In addition premature cranial suture closure, as seen in craniosynostosis (CS) and non-familial unilateral coronal synostosis (UCS), may be due to the overproduction of cranial membranous bone and the overexpression of NEL-2. To test this hypothesis, we propose the following specific aims: 1) Determining expression of NEL-2 in osteoblasts of non-familial UCS patients and at different stages of bone formation in vitro; 2) Determining the effect of NEL-2 on bone formation in vitro; 3) Determining the effect of NEL-2 on bone formation in human calvaria osteoblastic cells from CS patients; 4) Characterizing the regulation of NEL-2 expression; and 5) investigating the overexpression effect of NEL-2 on the rat cranial suture closure.
申请人建议研究NEL-2的功能,NEL-2是一种在颅突变(CS),骨形成和过早缝合闭合中分离的新基因。 CS会影响每3,000名婴儿中的大约一个,是与颅畸形相关的颅骨缝合线的过早闭塞。 我们已经分离和鉴定出其表达在患有普遍类型的CS,非家庭单侧冠状冠状动脉阴道(UCS)的患者的过早缝合融合位点上调。该基因的全长cDNA的核苷酸序列与鸡NEL基因具有约61%的同源性,因此被命名为该cDNA人NEL-2。 鸡NEL和人NEL-2都由6种EGF样重复组成。 我们证明了人NEL-2消息主要定位在间充质细胞中,成骨细胞在成骨锋,沿寄生的骨缘和新形成的骨的凝结间充质细胞中。 人NEL-2在胎儿大脑中特别表达,但在胎儿肺,肾脏或肝脏中不表达。 我们还表明,大鼠NEL-2在大鼠钙钙骨蛋白酶细胞中表达,并且在大鼠胫骨和成纤维细胞培养中很大程度上不存在。 构建表达大鼠NEL-2的哺乳动物表达向量并转染到MC3T3细胞系中。 与对照相比,观察到矿化的大约两倍半。另外,大鼠NEL-2的过表达诱导BMP-2基因表达。 我们的数据表明,NEL-2基因在颅内骨和神经组织中优先表达,并且可能与膜骨形成有关。 因此,我们假设NEL-2基因产物的过表达诱导了颅骨骨的过度生产。 此外,如在颅突(CS)和非家庭单侧冠状动脉突触(UCS)中所见,可能是由于颅骨骨骨的过度生产以及NEL-2的过表达所致。 为了检验这一假设,我们提出了以下特定目的:1)确定非家庭UCS患者成骨细胞中NEL-2的表达,并在体外的骨形成的不同阶段表达; 2)确定NEL-2对体外骨形成的影响; 3)确定NEL-2对CS患者的人颅骨细胞细胞中骨形成的影响; 4)表征NEL-2表达的调节; 5)研究NEL-2对大鼠颅缝合线闭合的过表达效应。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(12)
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{{ truncateString('KANG TING', 18)}}的其他基金
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- 批准号:
10156930 - 财政年份:2016
- 资助金额:
$ 12.13万 - 项目类别:
NELL-1, A Cbfa1 DOWNSTREAM TARGET, IN BONE FORMATION
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6899379 - 财政年份:2004
- 资助金额:
$ 12.13万 - 项目类别:
NELL-1, A Cbfa1 DOWNSTREAM TARGET, IN BONE FORMATION
NELL-1,Cbfa1 下游靶标,在骨形成中
- 批准号:
7253251 - 财政年份:2004
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$ 12.13万 - 项目类别:
NELL-1, A Cbfa1 DOWNSTREAM TARGET, IN BONE FORMATION
NELL-1,Cbfa1 下游靶标,在骨形成中
- 批准号:
6813346 - 财政年份:2004
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$ 12.13万 - 项目类别:
NELL-1, A Cbfa1 DOWNSTREAM TARGET, IN BONE FORMATION
NELL-1,Cbfa1 下游靶标,在骨形成中
- 批准号:
7071662 - 财政年份:2004
- 资助金额:
$ 12.13万 - 项目类别:
Nell-1, A Cbfa 1 Downstream Target, In Bone Formation
Nell-1,Cbfa 1 下游目标,在骨形成中
- 批准号:
7839166 - 财政年份:2004
- 资助金额:
$ 12.13万 - 项目类别:
NELL-1, A Cbfa1 DOWNSTREAM TARGET, IN BONE FORMATION
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- 批准号:
7456445 - 财政年份:2004
- 资助金额:
$ 12.13万 - 项目类别:
Mechanistic Role of NELL-1 in Premature Suture Closure
NELL-1 在缝线过早闭合中的机制作用
- 批准号:
6485869 - 财政年份:2002
- 资助金额:
$ 12.13万 - 项目类别:
Mechanistic Role of NELL-1 in Premature Suture Closure
NELL-1 在缝线过早闭合中的机制作用
- 批准号:
6651152 - 财政年份:2002
- 资助金额:
$ 12.13万 - 项目类别:
NEL-2 GENE IN BONE FORMATION & CRANIAL SUTURE CLOSURES
NEL-2 基因在骨形成中的作用
- 批准号:
6176897 - 财政年份:1999
- 资助金额:
$ 12.13万 - 项目类别:
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