70 research outputs found

    The IĸB protein BCL3 controls osteogenesis and bone health.

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    OBJECTIVE: IĸB protein B-cell lymphoma 3-encoded protein (BCL3) is a regulator of the NF-κB family of transcription factors. NF-κB signalling fundamentally influences the fate of bone-forming osteoblasts and bone-resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance and osteoarthritic pathology. METHODS: To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6-14) lacking BCL3 (Bcl3-/- ) and WT controls were characterised for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3-/- mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3-7) were assessed. Osteoclast differentiation and function in Bcl3-/- mice (n = 3-5) was assessed. Adult 20-week Bcl3-/- and WT mice bone phenotype, strength and turnover were assessed. A destabilisation of the medial meniscus (DMM) model of osteoarthritic ostephytogenesis was utilised to understand adult bone formation in Bcl3-/- mice (n = 11-13). RESULTS: Evaluation of Bcl3-/- mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength and altered bone turnover. Molecular and cellular characterisation of mesenchymal precursors showed that Bcl3-/- cells display an accelerated osteogenic transcriptional profile that leads to enhanced differentiation into osteoblasts with increased functional activity; which could be reversed with a mimetic peptide. In a model of osteoarthritis-induced osteophytogenesis, Bcl3-/- mice exhibit decreased pathological osteophyte formation (P < 0.05). CONCLUSION: Cumulatively, these findings demonstrate that BCL3 controls developmental mineralisation to enable appropriate bone formation, whilst in a pathological setting it contributes to skeletal pathology

    The IĸB protein BCL3 controls osteogenesis and bone health

    Get PDF
    Objective: IĸB protein B-cell lymphoma 3-encoded protein (BCL3) is a regulator of the NF-κB family of transcription factors. NF-κB signalling fundamentally influences the fate of bone-forming osteoblasts and bone-resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance and osteoarthritic pathology. Methods: To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6-14) lacking BCL3 (Bcl3−/−) and WT controls were characterised for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3−/− mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3-7) were assessed. Osteoclast differentiation and function in Bcl3−/− mice (n = 3-5) was assessed. Adult 20-week Bcl3−/− and WT mice bone phenotype, strength and turnover were assessed. A destabilisation of the medial meniscus (DMM) model of osteoarthritic ostephytogenesis was utilised to understand adult bone formation in Bcl3−/− mice (n = 11-13). Results: Evaluation of Bcl3−/− mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength and altered bone turnover. Molecular and cellular characterisation of mesenchymal precursors showed that Bcl3−/− cells display an accelerated osteogenic transcriptional profile that leads to enhanced differentiation into osteoblasts with increased functional activity; which could be reversed with a mimetic peptide. In a model of osteoarthritis-induced osteophytogenesis, Bcl3−/− mice exhibit decreased pathological osteophyte formation (P &lt; 0.05). Conclusion: Cumulatively, these findings demonstrate that BCL3 controls developmental mineralisation to enable appropriate bone formation, whilst in a pathological setting it contributes to skeletal pathology

    Behaviour of a biocompatible titanium alloy during orthogonal micro-cutting employing green machining techniques

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    The sustainability of a process is the objective of modern industries aiming to reduce waste in production, since consumers require high quality and efficiency with fair price. Thus, a good understanding of the process should be its starting point. The manufacture of dental implants is an example in which waste reduction is important for the reduction of prices due to the demand for great quality and accuracy. This study observed the behaviour of sustainable micro-cutting applied to the Ti-6Al-7Nb titanium alloy, considering the ploughing effect on minimum quantity lubrication (MQL) and high-speed machining (HSM) conditions. When compared with dry condition and low-speed cutting in orthogonal micro-cutting, the use of HSM in dry cutting was more efficient than using MQL. The dry condition presented lower surface roughness, whilst the cooled/lubricated condition presented lower burr formation.publishe
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