Biglycan: A novel modulator of osteoblast differentiation

描述（由申请人提供）：生物矿化是一个复杂的过程，由细胞、生长因子和一些关键的细胞外基质分子协调，阐明控制功能矿化基质形成和维持的因素对于理解矿化组织紊乱的原因至关重要。近年来的研究表明，biglycan （BGN）作为富含小亮氨酸的基质蛋白聚糖的一员，通过调节成骨细胞的分化，在骨形成/基质矿化中发挥作用。然而，其机制尚不清楚。本探索性研究旨在寻找BGN在成骨细胞分化和随后的基质矿化中的新调节作用。待验证的假设是BGN通过与骨形态发生蛋白-2的特异性相互作用促进成骨细胞分化/基质矿化。为了验证这一假设，将追求以下具体目标：(1)确定BGN与BMP-2的结合特异性；(2)研究BGN对bmp -2介导的成骨细胞分化的影响；(3)利用表达低水平BGN的成骨细胞MC3T3-E1细胞衍生克隆，确定BGN和BMP-2对成骨细胞分化和基质矿化的影响。从这项研究中获得的数据可能为基质调节成骨细胞分化和矿化组织形成的新途径提供见解。

DESCRIPTION (provided by applicant): Biomineralization is a complex process orchestrated by cells, growth factors and a number of key extracellular matrix molecules, and the elucidation of factors that control the formation and maintenance of the functional mineralized matrix is critical in understanding the cause of mineralized tissue disorders. Recent studies have indicated that biglycan (BGN), a member of small leucine rich matrix proteoglycans, plays a role in bone formation/matrix mineralization by modulating osteoblast differentiation. However, the mechanisms are not well understood. This exploratory research is intended to seek a novel modulatory role of BGN in osteoblast differentiation and subsequent matrix mineralization. The hypothesis to be tested is that BGN promotes osteoblast differentiation/matrix mineralization by through its specific interaction with bone morphogenetic protein (BMP)-2. To test this hypothesis the following specific aims will be pursued: (1) to determine the binding specificity of BGN to BMP-2; (2) to investigate the effects of BGN on BMP-2-mediated osteoblastic cell differentiation; and (3) to determine the effects of BGN and BMP-2 on osteoblastic cell differentiation and matrix mineralization using osteoblastic MC3T3-E1 cell-derived clones expressing lower levels of BGN. The data obtained from this study may provide insights into a novel pathway of matrix-modulated osteoblast differentiation and mineralized tissue formation.