Chen Xiao-Dong, Bian Xiaopeng, Teslovich Tanya M, Stephan Dietrich A, Young Marian F
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Bone. 2005 Aug;37(2):192-203. doi: 10.1016/j.bone.2005.04.006.
Biglycan (bgn) is a small leucine-rich proteoglycan (SLPR) that is enriched in the extracellular matrix of skeletal tissues. Bgn-deficient mice develop age-related osteopenia with a phenotype that resembles osteoporosis. In order to identify sets of genes that play a key role in the skeletal abnormality, we determined the global gene expression patterns in bgn-deficient (bgn-KO) pre-osteoblasts using oligonucleotide microarray technology. Calvarial cells were harvested from newborn mice and cultured in the presence or absence of BMP-4 for 7 days. The total RNA was purified, labeled and hybridized to Affymetrix chips (U74A), and analyzed with a software program called GeneSpring. Our data suggested that biglycan regulates the activity of osteoblastic progenitors through sets of genes associated with cell cycle, cell growth, and differentiation. The biological outcome from the altered expression of these genes could cause a defect in the quantity and quality of osteoblastic progenitors, which could contribute to the development of age-related osteopenia in bgn-KO mice. Moreover, the data from this approach also revealed that biglycan deficiency affected the genes that control inflammation, immune response, and growth of tumor cells. These are new and unexpected findings that lead to the formation of new paradigms for biglycan function. Based on these findings, we propose that the reduction of this small proteoglycan with aging may increase the risk of infection and autoimmune diseases, impair wound healing, and cause higher incidences of malignancy. This study provides a broad and deep foundation for understanding SLRP function at a more complex level.
双糖链蛋白聚糖（bgn）是一种富含亮氨酸的小分子蛋白聚糖（SLPR），在骨骼组织的细胞外基质中含量丰富。bgn基因缺陷小鼠会出现与年龄相关的骨质减少，其表型类似于骨质疏松症。为了确定在骨骼异常中起关键作用的基因集，我们使用寡核苷酸微阵列技术测定了bgn基因缺陷（bgn-KO）前成骨细胞中的全局基因表达模式。从新生小鼠中收集颅骨细胞，在有或无骨形态发生蛋白-4（BMP-4）的情况下培养7天。纯化总RNA，进行标记并与Affymetrix芯片（U74A）杂交，然后用名为GeneSpring的软件程序进行分析。我们的数据表明，双糖链蛋白聚糖通过与细胞周期、细胞生长和分化相关的基因集来调节成骨祖细胞的活性。这些基因表达改变所产生的生物学结果可能导致成骨祖细胞数量和质量出现缺陷，这可能促成bgn-KO小鼠中与年龄相关的骨质减少的发展。此外，该方法的数据还显示，双糖链蛋白聚糖缺乏会影响控制炎症、免疫反应和肿瘤细胞生长的基因。这些都是新的意外发现，为双糖链蛋白聚糖的功能形成了新的范例。基于这些发现我们提出，随着年龄增长这种小分子蛋白聚糖的减少可能会增加感染和自身免疫性疾病的风险，损害伤口愈合，并导致更高的恶性肿瘤发生率。这项研究为在更复杂层面理解SLRP的功能提供了广泛而深入的基础。
