Keratocan is expressed by osteoblasts and can modulate osteogenic differentiation.
Keratocan is expressed by osteoblasts and can modulate osteogenic differentiation.
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DOI：
10.3109/03008207.2010.546536
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发表时间：
2011-10
影响因子：
2.9
通讯作者：
Kalajzic I
中科院分区：
文献类型：
--
作者：
Igwe JC;Gao Q;Kizivat T;Kao WW;Kalajzic I
角质蛋白聚糖是属于富含亮氨酸的小蛋白聚糖家族的细胞外基质蛋白，该家族还包括光蛋白聚糖、双糖蛋白聚糖、核心蛋白聚糖、mimecan和纤调蛋白。已知该家族的成员在调节细胞过程如骨祖细胞谱系分化的增殖和调节中起作用。本研究的目的是评估角蛋白聚糖在骨祖细胞谱系中的表达模式，并评估其在调节成骨细胞成熟和功能中的作用。来自成骨细胞谱系内不同成熟阶段的细胞的基因表达分析的结果表明，成骨细胞差异表达角蛋白聚糖，而骨细胞几乎不表达或不表达角蛋白聚糖。在原代成骨细胞培养期间，在第14天观察到高的角膜蛋白聚糖mRNA表达，而在第7天和第21天检测到较低的表达。为了评估角膜蛋白聚糖对骨祖细胞分化的影响，我们评估了来自角膜蛋白聚糖缺陷小鼠的原代颅骨细胞培养物。来自keratocan null（kera−/−）小鼠的颅骨成骨细胞培养物的矿化低于野生型成骨细胞培养物。此外，对来源于kera−/−颅骨细胞培养物的RNA的分析显示，成熟成骨细胞分化标志物减少，即，骨涎蛋白（BSP）和骨钙素（OC）。此外，我们还评估了角蛋白聚糖缺陷小鼠的骨形成。组织形态计量学分析表明，纯合子敲除小鼠的骨形成率和矿物质沉积率显着降低。综上所述，我们的结果证明了成骨细胞系细胞表达角蛋白聚糖及其调节成骨细胞功能的能力。
Keratocan is an extracellular matrix protein that belongs to the small leucine-rich proteoglycan family which also includes the lumican, biglycan, decorin, mimecan and fibromodulin. Members of this family are known to play a role in regulating cellular processes such as proliferation and modulation of osteoprogenitor lineage differentiation. The aims of this study were to evaluate the expression pattern of the keratocan within the osteoprogenitor lineage and assess its role in regulating osteoblast maturation and function. Results from gene expression analyses of cells at different maturation stages within the osteoblast lineage indicate that keratocan is differentially expressed by osteoblasts and shows little or no expression by osteocytes. During primary osteoblast cultures, high keratocan mRNA expression was observed on day 14, while lower expression was detected at days 7 and 21. To assess the effects of keratocan on osteoprogenitor cell differentiation, we evaluated primary calvarial cell cultures from keratocan deficient mice. The mineralization of calvarial osteoblast cultures derived from keratocan null (kera−/−) mice was lower than in wild type osteoblast cultures. Furthermore, analysis of RNA derived from kera−/− calvarial cell cultures showed a reduction in the mature osteoblast differentiation markers, i.e., bone sialoprotein (BSP) and osteocalcin (OC). In addition, we have evaluated the bone formation in keratocan deficient mice. Histomorphometric analysis indicated that homozygous knockout mice have a significantly decreased rates of bone formation rate and mineral apposition. Taken together our results demonstrate the expression of keratocan by osteoblast lineage cells and its ability to modulate osteoblast function.