Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation
Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation
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DOI：
10.1359/jbmr.1998.13.4.633
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发表时间：
1998-04-01
影响因子：
6.2
通讯作者：
Civitelli, R
中科院分区：
文献类型：
--
作者：
Cheng, SL;Lecanda, F;Civitelli, R
直接的细胞间相互作用是组织发育和分化的基础，我们研究了体外分化过程中人成骨细胞中钙粘蛋白的表达和功能，利用逆转录聚合酶链反应和mRNA杂交，我们发现人小梁骨成骨细胞（HOB）、骨祖细胞骨髓基质细胞（BMC）和成骨肉瘤 SaOS-2 和 MG-63 系表达钙粘蛋白-II (C11) 和 N-钙粘蛋白 (N-cad) 的 mRNA。 HOB和BMC也表达低水平的钙粘蛋白4（C4）mRNA，C11是人成骨细胞中最丰富的钙粘蛋白，其表达不受BMC或HOB的骨形态发生蛋白2（BMP-2）处理的影响，同样，N-cad mRNA在BMP-2孵育期间没有变化，相反，C4蛋白在转化后检测不到。 细胞系，通过正常细胞的 BMP-2 处理下调，C11 和 C4 都定位于 HOB 和 BMC 中细胞与细胞接触的位点，与 β-连环蛋白共定位，并且与钙粘蛋白对应的条带通过 β-连环蛋白抗体共免疫沉淀，结果表明功能性钙粘蛋白，含有人 N-cad 的 HAV 基序的十肽 部分抑制 Ca2+ 依赖性细胞间粘附，并完全阻止 BMP-2 诱导的 BMC 碱性磷酸酶活性刺激，因此，人成骨细胞及其祖细胞表达多种钙粘蛋白，钙粘蛋白介导的细胞间粘附对于正常人成骨细胞分化至关重要。
Direct cell-cell interactions are fundamental for tissue development and differentiation, We have studied the expression and function of cadherins in human osteoblasts during in vitro differentiation, Using reverse transcription-polymerase chain reaction and mRNA hybridization, we found that human trabecular bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the osteogenic sarcoma lines, SaOS-2 and MG-63, expressed mRNA for cadherin-ll (C11) and N-cadherin (N-cad). HOBs and BMCs also expressed low levels of cadherin-4 (C4) mRNA, C11 was the most abundant cadherin protein present in human osteoblasts, and its expression was unaffected by bone morphogenetic protein-2 (BMP-2) treatment of either BMCs or HOBs, Likewise, N-cad mRNA did not change during BMP-2 incubation, Conversely, C4 protein, undetectable in transformed cell lines, was down-regulated by BMP-2 treatment of normal cells, Both C11 and C4 were localized to sites of cell-cell contact in both HOBs and BMCs, colocalized with beta-catenin, and bands corresponding to cadherins were coimmunoprecipitated by a beta-catenin antibody, findings indicative of functional cadherins, A decapeptide containing the HAV motif of human N-cad partially inhibited Ca2+-dependent cell-cell adhesion and completely prevented BMP-2-induced stimulation of alkaline phosphatase activity by BMCs, Thus, human osteoblasts and their progenitor cells express a repertoire of multiple cadherins, Cadherin-mediated cell-to-cell adhesion is critical for normal human osteoblast differentiation.