Nanotopographical Induction of Osteogenesis through Adhesion, Bone Morphogenic Protein Cosignaling, and Regulation of MicroRNAs

Abstract

It is emerging that nanotopographical information can be used to induce osteogenesis from mesenchymal stromal cells from the bone marrow, and it is hoped that this nanoscale bioactivity can be utilized to engineer next generation implants. However, the osteogenic mechanism of surfaces is currently poorly understood. In this report, we investigate mechanism and implicate bone morphogenic protein (BMP) in up-regulation of RUNX2 and show that RUNX2 and its regulatory miRNAs are BMP sensitive. Our data demonstrate that osteogenic nanotopography promotes colocalization of integrins and BMP2 receptors in order to enhance osteogenic activity and that vitronectin is important in this interface. This provides insight that topographical regulation of adhesion can have effects on signaling cascades outside of cytoskeletal signaling and that adhesions can have roles in augmenting BMP signaling.

Coordinated regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by endogenous bone morphogenetic proteins

“…The ultimate outcome may also be influenced by surface nanotopography [44], the response of other cell types around the implant to BMP2, and prove to be context-dependent. Moreover, a number of mechanisms may be responsible for an apparent BMP2 enhancement when MSCs are cultured on microtextured Ti, including the expression of microRNAs that influence BMP2 pathways [45–47]. The extent to which blocking extracellular BMP2 inhibitors can enhance osteogenesis in the context of microtextured Ti remains to be tested in vivo .…”

Analysis of Osteoblast Differentiation on Polymer Thin Films Embedded with Carbon Nanotubes

“…Expression of the β integrin subunits, β 1 and β 3 , was upregulated for both the 10% and 50% CNT/PCU surfaces (Fig 3I). According to the previous studies, role of integrin genes on the subsequent osteoblast differentiation [23–28] was discussed. In this study, up-regulation of specific integrin genes on CNT/PCU surfaces (at 4 hrs) may trigger later osteoblast differentiation through activating integrin-mediated signaling pathways.…”

Binding of integrin α1 to bone morphogenetic protein receptor IA suggests a novel role of integrin α1β1 in bone morphogenetic protein 2 signalling

“…BMPR IA, which phosphorylates Smad in the BMP signalling pathway, was suggested to form a complex with different integrins (Lai et al, 2005;Yang et al, 2014). Thus, we proposed that a functional relationship existed between these two signaling pathways.…”

“…Yang et al (2014) showed that nano-topography promotes co-localisation of integrin β5 and BMP2 receptors; therefore, research into how co-localisation of integrin and BMPR is regulated will be important for gaining a deeper understanding of the role played by the complex. Moreover, clarification of the regulation and downstream effects of the interaction between BMPR IA and integrin α1 may also uncover novel mechanisms by which these proteins could be targeted for therapeutic benefits.…”

“…Lai et al (2005) found that certain integrins, including αvβ1, αvβ3, αvβ5, αvβ8, co-localized with BMPRs in human U-2 OS osteosarcoma cells. Yang et al (2014) demonstrated that integrin β5 co-localized with BMPR IA in human bone marrow mesenchymal stem cells (hBMMSCs). Having taken the previously reported results regarding certain integrins and BMPRs into consideration, we ask whether α1 subunit can co-localise and interact with BMPR IA via the A-domain.…”