Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants
Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants
复制标题
DOI：
10.1002/jbm.10270
复制
发表时间：
2002-11-01
期刊：
影响因子：
--
通讯作者：
Shakibaei, M
中科院分区：
文献类型：
--
作者：
Zreiqat, H;Howlett, CR;Shakibaei, M
细胞与骨科和牙科植入物的粘附性差可能导致植入物失败。细胞粘附到生物材料表面主要是由整合素介导的，整合素充当信号转导和粘附蛋白。由于整合素的功能依赖于二价阳离子，我们研究了镁离子修饰的生物陶瓷基质（Al 2 O3-Mg 2+）对人骨源性细胞（HBDC）粘附，整合素表达和细胞内信号分子活化的影响。采用免疫组化、流式细胞术、细胞粘附、细胞粘附阻断和Western印迹分析。我们的研究结果表明，HBDC对Al 2 O3-Mg 2+的粘附性比在无Mg 2+的Al 2 O3上增加。此外，当纤连蛋白受体α 5 β 1-和β 1-整合素被功能性阻断抗体阻断时，HBDC粘附显著降低。与在天然未修饰的Al 2 O3上生长的HBDC相比，在Mg 2+修饰的生物陶瓷上生长的HBDC表达显著增强的β 1-、α 5 β 1-和α 3 β 1-整合素受体水平。当HBDC在Al 2 O3-Mg 2+上生长时，与天然Al 2 O3相比，细胞内整合素依赖性信号蛋白的酪氨酸磷酸化以及关键信号蛋白Shc亚型（p46，p52，p66），粘着斑激酶和细胞外基质蛋白I型胶原的表达显著增强。我们的结论是，细胞粘附到生物材料表面可能是由α 5 β 1-和β 1-整合素介导的。阳离子促进的细胞粘附依赖于5 β 1-和β 1-整联蛋白相关的信号转导途径，涉及关键信号蛋白Shc，并导致细胞外基质蛋白的基因表达增强。因此，生物陶瓷基质的Mg 2+补充可能是一种有前途的方法，以改善骨科和牙科手术中植入物的整合。(C)2002 Wiley Periodicals，Inc.
Poor cell adhesion to orthopaedic and dental implants may result in implant failure. Cellular adhesion to biomaterial surfaces primarily is mediated by integrins, which act as signal transduction and adhesion proteins. Because integrin function depends on divalent cations, we investigated the effect of magnesium ions modified bioceramic substrata (Al2O3-Mg2+) on human bone-derived cell (HBDC) adhesion, integrin expression, and activation of intracellular signalling molecules. Immunohistochemistry, flow cytometry, cell adhesion, cell adhesion blocking, and Western blotting assays were used. Our findings demonstrated that adhesion of HBDC to Al2O3-Mg2+ was increased compared to on the Mg2+-free Al2O3. Furthermore, HBDC adhesion decreased significantly when the fibronectin receptor alpha5beta1-and beta1-integrins were blocked by functional blocking antibodies. HBDC grown on the Mg2+-modified bioceramic expressed significantly enhanced levels of beta1-, alpha5beta1-, and alpha3beta1-integrins receptors compared to those grown on the native unmodified Al2O3. Tyrosine phosphorylation of intracellular integrin-dependent signalling proteins as well as the expression of key signalling protein Shc isoforms (p46, p52, p66), focal adhesion kinase, and extracellular matrix protein collagen type I were significantly enhanced when HBDC were grown on Al2O3-Mg2+ compared to the native Al2O3. We conclude that cell adhesion to biomaterial surfaces is probably mediated by alpha5beta1- and beta1-integrin. Cation-promoted cell adhesion depends on 5beta1- and beta1-integrins associated signal transduction pathways involving the key signalling protein Shc and results also in enhanced gene expression of extracellular matrix proteins. Therefore, Mg2+ supplementation of bioceramic substrata may be a promising way to improve integration of implants in orthopaedic and dental surgery. (C) 2002 Wiley Periodicals, Inc.