Post-graduation Program in Dentistry, School of Health Sciences, UNIGRANRIO, Duque de Caxias, Rio de Janeiro, Brazil.
J Biomed Mater Res A. 2011 May;97(2):193-200. doi: 10.1002/jbm.a.32933. Epub 2011 Mar 10.
Several biomaterials have been widely used in bone regeneration in both orthopedic and oral surgeries. However, it is poorly understood how these biomaterials alter osteoblast phenotype. It prompted us to examine the involvement of signaling proteins during preosteoblast adhesion (attachment), proliferation, and differentiation on natural hydroxyapatite (HA) from bovine bone. Our results indicated that natural HA is able to promote osteoblast adhesion, proliferation, and differentiation. The osteoblast/HA interaction requires phosphorylation of tyrosine residues of focal adhesion kinase, Src, and Paxillin upon integrin activation, which culminates in the control of cofilin phosphorylation (at serine 03) via rac-1 activation. In part, these signaling pathways are responsible for actin-rearrangement, responsible to adapt cell-shape on HA particles. In regarding to osteoblast differentiation, we showed that natural HA favored extracellular matrix remodeling by stimulating matrix metalloproteinase activities and alkaline phosphatase activity. Overall, this study demonstrates that osteoblast response toward bovine bone HA is initially mediated by activation of focal adhesion components, culminating on actin-rearrangement executed by cofilin activation via rac-1. Moreover, bovine bone HA provided an excellent microenvironment for osteoblast activity, since adhesion to differentiation.
几种生物材料已广泛应用于骨科和口腔外科的骨再生中。然而，人们对这些生物材料如何改变成骨细胞表型知之甚少。这促使我们研究在天然牛骨羟磷灰石（HA）上，前成骨细胞黏附（附着）、增殖和分化过程中信号蛋白的参与。我们的结果表明，天然 HA 能够促进成骨细胞的黏附、增殖和分化。成骨细胞/HA 的相互作用需要整合素激活时粘着斑激酶、Src 和桩蛋白酪氨酸残基的磷酸化，最终通过 rac-1 的激活来控制丝切蛋白磷酸化（丝氨酸 03）。在某种程度上，这些信号通路负责肌动蛋白的重排，负责适应 HA 颗粒上的细胞形状。至于成骨细胞分化，我们发现天然 HA 通过刺激基质金属蛋白酶活性和碱性磷酸酶活性来促进细胞外基质的重塑。总的来说，这项研究表明，成骨细胞对牛骨 HA 的反应最初是通过粘着斑成分的激活来介导的，最终通过 rac-1 激活丝切蛋白来执行肌动蛋白的重排。此外，牛骨 HA 为成骨细胞的活性提供了极好的微环境，因为从黏附到分化。
