Titanium dioxide nanotubes of defined diameter enhance mesenchymal stem cell proliferation via JNK- and ERK-dependent up-regulation of fibroblast growth factor-2 by T lymphocytes

Abstract

Long-term clinical success of a titanium implant not only depends upon osseointegration between implant and bone surface but also on the response of host immune cells. Following implantation of biomaterials, an inflammatory response, including T lymphocyte response, is ostensibly initiated by implant-cell interaction. However, little is known about the responses of T lymphocytes to titanium dioxide nanotubes. The present study aimed to explore the effect of titanium dioxide nanotubes on T lymphocytes in vitro and its biological consequences. The results of the present study showed that titanium dioxide nanotubes with diameter of 30–105 nm were non-cytotoxic to T lymphocytes, and the 105 nm titanium dioxide nanotube surface specifically possessed an ability to activate T lymphocytes, thus increasing DNA synthesis and cell proliferation. In addition, the 105 nm titanium dioxide nanotubes significantly activated the expression of FGF-2 gene and protein in T lymphocytes although smaller nanotubes (i.e. those with diameters of approximately 30 and 70 nm) had little effect on this. The present study investigated the mechanism by which 105 nm nanotubes stimulated FGF-2 expression in T lymphocytes by blocking key MAPK pathways. The inhibitors of JNK1/2/3 and ERK1/2 significantly inhibited 105 nm titanium dioxide nanotubes-induced FGF-2 expression. Corresponding to the increased expression of FGF-2, only the supernatant from T lymphocytes cultured on 105 nm nanotubes stimulated human mesenchymal stem cell proliferation. FGF-2 blocking antibody partially reversed the increased proliferation of human mesenchymal stem cells, supporting the role of T lymphocyte-derived FGF-2 in enhanced human mesenchymal stem cell proliferation. This suggests a significant role of T lymphocyte-titanium dioxide nanotube interaction in the proliferation of human mesenchymal stem cells, which is pivotal to the formation of new bone following implant placement.

Surface modification of titanium manufactured through selective laser melting inhibited osteoclast differentiation through mitogen-activated protein kinase signaling pathway

“…We inferred that the suppression of ERK and JNK phosphorylation in the SLA group may be attributed to other upstream signals related to cell proliferation and survival, such as GRB2 and TRAF2, instead of TRAF6. [74][75][76] It was in agreement with the result that SLA inhibited the cell proliferation. The other signaling pathways merit further study to clarify their underlying mechanisms.…”

Nanostructured Titanium Implant Surface Facilitating Osseointegration from Protein Adsorption to Osteogenesis: The Example of TiO2 NTAs

“…TiO 2 NTAs can activate T lymphocytes and induce the expression of fibroblast growth factor-2 (FGF-2) by blocking key MAPK signaling pathways; however, the optimal nanotube diameter is 105 nm, rather than the optimal diameter of 15 nm for macrophage M2-polarization. 42 , 98 M2-polarization facilitates osseointegration, while T lymphocyte plays a vital role in fibrosis. 99 Therefore, we can deeply investigate the difference in the optimal TiO 2 NTAs diameters of the two cells, and try to increase M2-polarization and decrease T lymphocyte activation, to avoid fibrotic encapsulation forming around the implant and facilitate osseointegration.…”

Qelizat burimore mezenkimale, reagimi ndaj sipërfaqeve implantare drejt osteointegrimit

“…Artikuj ku ёshtё vlerёsuar efekti i modulimit tё sipёrfaqes implante in vivo tek pacientёt, nё total janё 4 artikuj. (65)(66)(67)(68) Në përmbledhje të artikujve të përzgjedhur kundrejt faktit se cila metodë është përdorur për të ndryshuar përmbajtjen sipërfaqësore implantare listojmë:…”