Osteoadherin is upregulated by mature osteoblasts and enhances their in vitro differentiation and mineralization
Osteoadherin is upregulated by mature osteoblasts and enhances their in vitro differentiation and mineralization
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DOI：
10.1007/s00223-008-9138-1
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Wendel, Mikael
中科院分区：
文献类型：
--
作者：
Rehn, Anders P.;Cerny, Radim;Wendel, Mikael
在分化过程中，成骨细胞在几种生长因子、细胞因子和细胞外基质（ECM）蛋白的影响下通过严格控制的检查点进行定向。矿化的组织特异性ECM成分骨粘附素（OSAD）属于富含亮氨酸的小重复蛋白家族的蛋白聚糖。蛋白聚糖通过所连接的糖胺聚糖链或通过经由核心蛋白质序列的直接蛋白质-蛋白质相互作用来调节细胞行为。富含亮氨酸的重复序列已被证明与细胞表面受体如表皮生长因子受体直接相互作用，阻断其结合其配体的能力。在本研究中，我们研究了OSAD对MC 3 T3 EI成骨细胞的行为和成熟的影响。通过用编码小鼠OSAD cDNA或针对小鼠OSAD的小发夹RNA的质粒稳定转染来产生OSAD过表达和抑制克隆。OSAD的过表达导致成骨细胞分化特征的增加，例如碱性磷酸酶（ALP）活性增加和体外矿化增加，以及增殖和迁移减少。骨唾液蛋白（BSP）水平不变，而骨钙素（OC）和骨甘氨酸（OGN）的上调。相反，抑制OSAD表达导致细胞增殖和迁移增加。BSP和OC不受影响，而OGN下调。ALP活性降低，但没有观察到体外矿化的变化。我们的结论是，OSAD过表达促进体外成骨细胞的分化和成熟。
During the process of differentiation, osteoblasts commit through strictly controlled checkpoints under the influence of several growth factors, cytokines, and extracellular matrix (ECM) proteins. The mineralized tissue-specific ECM component osteoadherin (OSAD) belongs to the small leucine-rich repeat protein family of proteoglycans. Proteoglycans modulate cellular behavior either through the attached glycosaminoglycan chains or by direct protein-protein interactions via the core protein sequences. Leucine-rich repeats have been shown to directly interact with cell-surface receptors such as epidermal growth factor receptor, blocking its ability to bind its ligand. In the present study, we investigated the influence of OSAD on the behavior and maturation of MC3T3EI osteoblasts. OSAD overexpression and repression clones were created by stably transfecting with plasmids coding for either mouse OSAD cDNA or small-hairpin RNA, targeted against mouse OSAD. Overexpression of OSAD resulted in an increase of osteoblast differentiation features, such as increased alkaline phosphatase (ALP) activity and increased in vitro mineralization, as well as reduced proliferation and migration. Bone sialoprotein (BSP) levels were unchanged, while upregulation of osteocalcin (OC) and osteoglycin (OGN) was observed. Conversely, repression of OSAD expression resulted in increased cell proliferation and migration. BSP and OC were unaffected, while OGN was downregulated. ALP activity was reduced, though no change in in vitro mineralization was observed. We conclude that OSAD overexpression enhanced the differentiation and maturation of osteoblasts in vitro.