Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.We acknowledge funding from an EPSRC Platform grant which supported McMurray and a Wellcome Trust project grant which supported Wann and McMurray. Wann is now supported on an ARUK project grant. Thompson was funded by a BBSRC PhD studentshi

Strontium substituted bioactive glasses for tissue engineered scaffolds: the importance of octacalcium phosphate

Porous bioactive glasses are attractive for use as bone scaffolds. There is increasing interest in strontium containing bone grafts, since strontium ions are known to up-regulate osteoblasts and down regulate osteoclasts. This paper investigates the influence of partial to full substitution of strontium for calcium on the dissolution and phase formation of a multicomponent high phosphate content bioactive glass. The glasses were synthesised by a high temperature melt quench route and ground to a powder of <38 microns. The dissolution of this powder and its ability to form apatite like phases after immersion in Tris buffer (pH 7.4) and simulated body fluid (SBF) was followed by inductively coupled plasma optical emission spectroscopy (ICP), Fourier transform infra red spectroscopy (FTIR), X-ray powder diffraction (XRD) and (31)P solid state nuclear magnetic resonance spectroscopy up to 42 days of immersion. ICP indicated that all three glasses dissolved at approximately the same rate. The all calcium (SP-0Sr-35Ca) glass showed evidence of apatite like phase formation in both Tris buffer and SBF, as demonstrated after 3 days by FTIR and XRD analysis of the precipitate that formed during the acellular dissolution bioactivity studies. The strontium substituted SP-17Sr-17Ca glass showed no clear evidence of apatite like phase formation in Tris, but evidence of an apatite like phase was observed after 7 days incubation in SBF. The SP-35Sr-0Ca glass formed a new crystalline phase termed “X Phase” in Tris buffer which FTIR indicated was a form of crystalline orthophosphate. The SP-35Sr-0Ca glass appeared to support apatite like phase formation in SBF by 28 days incubation. The results indicate that strontium substitution for calcium in high phosphate content bioactive glasses can retard apatite like phase formation. It is proposed that apatite formation with high phosphate bioactive glasses occurs via an octacalcium phosphate (OCP) precursor phase that subsequently transforms to apatite. The equivalent octa-strontium phosphate does not exist and consequently in the absence of calcium, apatite formation does not occur. The amount of strontium that can be substituted for calcium in OCP probably determines the amount of strontium in the final apatite phase and the speed with which it forms

Minimally invasive total knee replacement : techniques and results

In this review, we outlined the definition of minimally invasive surgery (MIS) in total knee replacement (TKR) and described the different surgical approaches reported in the literature. Afterwards we went through the most recent studies assessing MIS TKR. Next, we searched for potential limitations of MIS knee replacement and tried to answer the following questions: Are there selective criteria and specific patient selection for MIS knee surgery? If there are, then what are they? After all, a discussion and conclusion completed this article. There is certainly room for MIS or at least less invasive surgery (LIS) for appropriate selected patients. Nonetheless, there are differences between approaches. Mini medial parapatellar is easy to master, quick to perform and potentially extendable, whereas mini subvastus and mini midvastus are trickier and require more caution related to risk of hematoma and VMO nerve damage. Current evidence on the safety and efficacy of mini-incision surgery for TKR does not appear fully adequate for the procedure to be used without special arrangements for consent and for audit or continuing research. There is an argument that a sudden jump from standard TKR to MIS TKR, especially without computer assistance such as navigation, patient specific instrumentation (PSI) or robotic, may breach a surgeon's duty of care toward patients because it exposes patients to unnecessary risks. As a final point, more evidence is required on the long-term safety and efficacy of this procedure which will give objective shed light on real benefits of MIS TKR