Functional analysis of the novel target gene of bone volume-regulating transcription factor Schnurri-3.

骨质疏松症是成人骨形成和吸收不平衡的结果。虽然Schnurri 3（Shn3）负调节成年小鼠的骨体积，但其潜在的分子机制尚未完全了解。我们通过基因芯片的方法寻找Shn3基因敲低对成骨细胞中基因表达水平的影响，发现Alg 2是由Shn3诱导的。Alg2与成骨细胞分化主调节因子Runx2发生物理相互作用，干扰其核定位，导致其转录活性受到抑制。在软骨细胞中，Alg2诱导Creb3l2，这是一个重要的生理性内质网应激在软骨形成过程中的关键基因，以支持软骨细胞的成熟。我们的研究结果揭示了一种新的可能性，即甘露糖基转移酶基因在骨和软骨细胞的基因转录和表达中起着至关重要的作用。

Osteoporosis is a result of unbalanced bone formation and resorption in adult bone. Although Schnurri 3 (Shn3) negatively regulates bone volume in adult mice, the underlying molecular mechanism are not fully understood. We searched for genes which expression level were affected by knockdown of Shn3 in osteoblasts by microarray approach, and found that Alg2 was induced by Shn3. Alg2 physically interacted with the osteoblast differentiation master regulator Runx2 to interfere its nuclear localization, which resulted in its suppressed transcriptional activity. In chondrocytes, Alg2 induced Creb3l2, which is a crucial gene in the important physiological endoplasmic reticulum stress during chondrogenesis, to support chondrocyte maturation. Our findings revealed a novel possibility that mannosyltransferase genes play crucial roles in gene transcription and expression in cells of bone and cartilage.