Regulatory mechanism of the type XI collagen expression in osteoblasts

XI型胶原是由α 1（XI）、α 2（XI）和α 3（XI）三条遗传上不同的α链组成的异源三聚体，对胶原原纤维的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，但在骨组织或成骨细胞中也有大量表达的报道。虽然α 2型胶原基因（COL11A2）的转录机制已经在成软骨细胞中得到了很好的记录，但成骨细胞尚未得到研究。在本研究中，我们发现，在Sp1家族转录因子Sp1、Sp3和Sp7/Osterix的控制下，人类骨肉瘤衍生细胞系Saos-2细胞和正常人类成骨细胞原代培养物通过Sp1近端启动子的三个功能性结合位点表达COL11A2 mRNA （JBMR 2006）。此外，我们分析了MG63细胞，一种人骨肉瘤衍生的成骨细胞系，发现Sp7/Osterix专门增强了MG63细胞中COL11A2启动子的活性。Sp1和Sp3表达模式普遍存在，调控着广泛的细胞功能。相反，Sp7/Osterix表现为骨组织特异性表达，对成骨细胞分化和骨形成至关重要。在这里，我们证明了COL11A2的转录受到Sp1家族成员Sp1、Sp3和Sp7/Osterix在各种成骨细胞中的不同贡献的调节。综上所述，Sp1家族成员激活COL11A2似乎在各种成骨细胞中都很常见。Sp1家族成员在不同细胞中的不同作用的原因还有待阐明。

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.