The roles of Wnt signaling modulators Dickkopf-1 (Dkk1) and Dickkopf-2 (Dkk2) and cell maturation state in osteogenesis on microstructured titanium surfaces.
The roles of Wnt signaling modulators Dickkopf-1 (Dkk1) and Dickkopf-2 (Dkk2) and cell maturation state in osteogenesis on microstructured titanium surfaces.
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DOI：
10.1016/j.biomaterials.2009.11.071
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发表时间：
2010-03
期刊：
影响因子：
14
通讯作者：
Schwartz, Zvi
中科院分区：
文献类型：
--
作者：
Olivares-Navarrete, Rene;Hyzy, Sharon;Wieland, Marco;Boyan, Barbara D.;Schwartz, Zvi
成骨细胞在组织培养聚苯乙烯(TCPS)上的分化需要Wnt/β-catenin信号，调节Wnt途径的调节物，如Dickkopf-1(Dkk1)和Dkk2。与TCP相比，微结构钛表面的成骨细胞分化增强；因此，我们假设表面形貌和亲水性影响Dkk1和Dkk2的表达，并且它们在钛表面成骨细胞分化中的作用因细胞成熟状态而异。将人成骨样MG63细胞、正常人成骨细胞(HOBS)、人间充质干细胞(MSCs)以及稳定表达DKK1或DKK2的MG63细胞分别在钛表面(PT[Ra<；0.2μm]、SLA[Ra=4μm]、modSLA[Ha-Sla])上培养6d。Dkk1和Dkk2在SLA和modSLA上的mRNA和蛋白表达均增加，但外源性的rh Dkk1和rh Dkk2对MSCs的影响不同于MG63细胞和HOBS。沉默Dkk1减少了TCPS和PT上的MG63细胞数，但增加了这些底物上的分化。沉默Dkk2降低了SLA和modSLA对成骨细胞分化的刺激作用；Dkk2而不是Dkk1恢复了这些作用。针对Dkk1或Dkk2的抗体专门阻断了由这些蛋白质引起的底物依赖的变化，展示了它们的自分泌作用。这表明Dkk1和典型的Wnt通路在早期分化中起主要作用，Dkk2和Wnt/Ca~(2+)依赖的信号在微结构和亲水性表面的晚期分化中起主要作用。
Osteoblast differentiation on tissue culture polystyrene (TCPS) requires Wnt/beta-catenin signaling, regulating modulators of the Wnt pathway like Dickkopf-1 (Dkk1) and Dkk2. Osteoblast differentiation is increased on microstructured titanium (Ti) surfaces compared to TCPS; therefore, we hypothesized that surface topography and hydrophilicity affect Dkk1 and Dkk2 expression and that their roles in osteoblast differentiation on Ti differs depending on cell maturation state. Human osteoblast-like MG63 cells, normal human osteoblasts (HOBs), and human mesenchymal stem cells (MSCs), as well as MG63 cells stably silenced for Dkk1 or Dkk2 were grown for 6 days on TCPS and Ti surfaces (PT [Ra<0.2 μm], SLA [Ra = 4 μm], modSLA [hydrophilic-SLA]). Dkk1 and Dkk2 mRNA and protein increased on SLA and modSLA for all cell types, but exogenous rhDkk1 and rhDkk2 affected MSCs differently than MG63 cells and HOBs. Silencing Dkk1 reduced MG63 cell number on TCPS and PT, but increased differentiation on these substrates. Silencing Dkk2 reduced stimulatory effects of SLA and modSLA on osteoblast differentiation; Dkk2 but not Dkk1 restored these effects. Antibodies to Dkk1 or Dkk2 specifically blocked substrate-dependent changes caused by the proteins, demonstrating their autocrine action. This indicates major roles for Dkk1 and the canonical Wnt pathway in early-stage differentiation, and for Dkk2 and Wnt/Ca2+-dependent signaling in late-stage differentiation on microstructured and hydrophilic surfaces, during osseointegration.
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影响因子：
4.3
作者：
Cochran, DL;Nummikoski, PV;Buser, D
通讯作者：
Buser, D
影响因子：
4.3
作者：
Cochran, DL;Buser, D;Simpson, JP
通讯作者：
Simpson, JP
DOI：
10.1073/pnas.0805420105
发表时间：
2008-10-14
影响因子：
11.1
作者：
Olivares-Navarrete, R.;Raz, P.;Schwartz, Z.
通讯作者：
Schwartz, Z.
影响因子：
8.2
作者：
Bodine, Peter V. N.;Komm, Barry S.
通讯作者：
Komm, Barry S.
DOI：
10.1002/jbm.10290
发表时间：
2002-11-01
期刊：
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子：
--
作者：
Lohmann, CH;Tandy, EM;Schwartz, Z
通讯作者：
Schwartz, Z