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Regulatory mechanism of the type XI collagen expression in osteoblasts

成骨细胞XI型胶原表达的调控机制

基本信息

批准号：
18591664
负责人：
MATSUI Yoshito
金额：
$ 2.51万
依托单位：
Research Institute, Osaka Medical Center for Maternal and Child Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591664/
关键词：
osteoblast collagen gene regulation molecular biology regenerative medicine

项目摘要

Type XI collagen is a heterotrimer of three genetically distinct alpha chains, alpha 1(XI), alpha 2(XI) and alpha 3(XI), and is crucial for collagen fibril formation and skeletal morphogenesis. Type XI collagen is mostly found in cartilaginous tissues or in chondroblastic cells but its significant expression in osseous tissues or in osteoblastic cells has also been reported. Although transcriptional mechanisms for the alpha 2 type XI collagen gene(COL11A2) have been well documented in chondroblastic cells, osteoblastic cells have not been studied. In this study, we found that Saos-2 cells, a human osteosarcoma derived cell line, and primary cultures of normal human osteoblasts express COL11A2 mRNA under the control of Sp1 family of transcription factors, Sp1, Sp3 and Sp7/Osterix, through three functional Sp1 binding sites in the proximal promoter(JBMR 2006). Furthermore, we analyzed MG63 cells, a human osteosarcoma derived osteoblastic cell line, and found that Sp7/Osterix exclusively enhanced COL11A2 promoter activity in MG63 cells. Sp1 and Sp3 show ubiquitous expression pattern, and regulate a wide range of cellular function. In contrast, Sp7/Osterix shows bone tissue specific expression, and is essential for osteoblast differentiation and bone formation. Here we demonstrated that COL11A2 transcription is regulated by different contribution of the three Sp1 family members, Sp1, Sp3 and Sp7/Osterix, in various osteoblastic cells. In summary, the COL11A2 activation by Sp1 family members seems to be common in various osteoblastic cells. The reason for the different contribution of each Sp1 family member in various cells remains to be elucidated.

XI 型胶原蛋白是三个遗传上不同的 α 链 α 1(XI)、α 2(XI) 和 α 3(XI) 的异三聚体，对于胶原纤维形成和骨骼形态发生至关重要。 XI型胶原主要存在于软骨组织或成软骨细胞中，但也有报道称其在骨组织或成骨细胞中显着表达。尽管 α2 XI 型胶原基因 (COL11A2) 的转录机制已在成软骨细胞中得到充分记录，但尚未对成骨细胞进行研究。在这项研究中，我们发现 Saos-2 细胞（一种人骨肉瘤来源的细胞系）和正常人成骨细胞的原代培养物在转录因子 Sp1 家族 Sp1、Sp3 和 Sp7/Osterix 的控制下，通过近端启动子中的三个功能性 Sp1 结合位点表达 COL11A2 mRNA（JBMR 2006）。此外，我们分析了 MG63 细胞（一种人骨肉瘤来源的成骨细胞系），发现 Sp7/Osterix 专门增强了 MG63 细胞中的 COL11A2 启动子活性。 Sp1 和 Sp3 显示出普遍存在的表达模式，并调节广泛的细胞功能。相比之下，Sp7/Osterix 显示骨组织特异性表达，并且对于成骨细胞分化和骨形成至关重要。在这里，我们证明了在各种成骨细胞中，COL11A2 转录受到三个 Sp1 家族成员 Sp1、Sp3 和 Sp7/Osterix 的不同贡献的调节。总之，Sp1 家族成员对 COL11A2 的激活似乎在各种成骨细胞中很常见。每个 Sp1 家族成员在不同细胞中的不同贡献的原因仍有待阐明。