Targeting phosphatidylinositol-3-kinase for inhibiting maxillary bone resorption.

Previous studies have suggested a role of phosphatidylinositol-3-kinase gamma (PI3Kγ) in bone remodeling, but the mechanism remains undefined. Here, we explored the contribution of PI3Kγ in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic-induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3Kγ-deficient mice (PI3Kγ-/- ), mice with loss of PI3Kγ kinase activity (PI3KγKD/KD ) and C57BL/6 mice treated with a PI3Kγ inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3Kγ-/- , PI3KγKD/KD , and C57BL/6 mice treated with AS605240 showed an improvement of bone quality compared to their controls, resulting in reduction of the OTM and RME in all experimental groups. PI3Kγ-/- mice exhibited increased root volume and decreased odontoclasts counts. Consistently, the pharmacological blockade or genetic deletion of PI3K resulted in increased numbers of osteoblasts and reduction in osteoclasts during OTM. There was an augmented expression of Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (Alp), a reduction of interleukin-6 (Il-6), as well as a lack of responsiveness of receptor activator of nuclear factor kappa-Β (Rank) in PI3Kγ-/- and PI3KγKD/KD mice compared to control mice. The maxillary bones of PI3Kγ-/- animals showed reduced p-Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3Kγ-/- mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3Kγ/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.

Effects of manganese incorporation on the morphology, structure and cytotoxicity of spherical bioactive glass nanoparticles.

Bioactive glass nanoparticles (BGNPs) are of great interest in tissue engineering as they possess high dissolution rate and capability of being internalized by cells, releasing their dissolution products with therapeutic benefits intracellularly. A modified Stöber process can be applied to obtain different BGNPs compositions containing therapeutic ions while maintaining controllable particle morphology, monodispersity and reduce agglomeration. Here, BGNPs containing Mn, an ion that has been shown to influence the osteoblast proliferation and bone mineralization, were evaluated. Particles with up to 142.3 ±â€¯10.8 nm and spherical morphology were obtained after MnO incorporation in the SiO2 - CaO system. X-ray photoelectron spectroscopy (XPS) indicated the presence of Mn2+ species and also a reduction in the number of bridging oxygen bonds due to the Ca and Mn. The Ca and Mn network modifier role on the silica network was also confirmed by magic-angle spinning 29Si solid-state nuclear magnetic resonance (MAS NMR). MTT evaluation showed no reduction in the mitochondrial metabolic activity of human mesenchymal stem cells exposed to the glass ionic products. Thus, evaluation showed that Mn could be incorporated into BGNPs by the modified Stöber method while maintaining their spherical morphology and features as a promising strategy for tissue regeneration.

Glycol chitosan/nanohydroxyapatite biocomposites for potential bone tissue engineering and regenerative medicine.

In the last few decades, research on biocomposite nanomaterials has grown exponentially due to the global demand for novel solutions in bone tissue engineering and repair. In the present study, it is reported the design and synthesis of biocomposites based on glycol chitosan (GLY-CHI) matrices incorporated with nano-hydroxyapatite particles (nHA) produced via an eco-friendly chemical colloidal process in water media followed by solvent casting and evaporation methods at room temperature. The structure, morphology, and crystallinity of the components and biocomposites were extensively characterized by light microscopy (LM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), wavelength dispersive X-ray fluorescence spectroscopy (WD-XRF), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray micro-computed tomography analysis (µCT). Furthermore, cytotoxicity and cell viability tests were performed on three cell lines using a 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyl tetrazolium bromide (MTT) assay, an alkaline phosphatase (ALP) activity test, and LIVE/DEAD® assays. The results demonstrated that the GLY-CHI ligand played a major role in the nucleation, growth and colloidal stabilization of calcium phosphate particles at nanoscale dimensions with a narrow distribution and average size of 74±15nm. The FTIR spectroscopy associated with the XRD results indicated that nanosized hydroxyapatite (nHA) was the predominant calcium phosphate phase produced in the colloidal processing route. In addition, the X-ray micro-CT analysis of the nanocomposite membranes showed that nHA particles were homogenously dispersed in the glycol-chitosan polymeric matrix. Moreover, according to the in vitro bioassays, the biocomposites showed an adequate cell viability response and non-cytotoxic behavior toward osteoblastic-like (SAOS) and embryonic cell lines (HEK293T). Finally, the results of osteogenic differentiation tests demonstrated that the nHA/GLY-CHI composites are osteoinductive for human bone marrow mesenchymal stem cells (HBMS), which can be envisioned for prospective use in tissue engineering (e.g., bone, cartilage and periodontal) applications.