Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice

Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss

Tracing the evolution and charting the future of geothermal energy research and development

The gamut of geothermal energy research encompasses the studies aimed at harnessing the abundant and inexhaustible thermal energy within the Earth, and it ranges from heat transfer to the activity of thermophilic microorganisms, 3D printing, and additive manufacturing and impacts the NET ZERO endeavour of humanity. In this paper, computational social network analysis has been employed to discover the subfield clusters of geothermal energy research and further trace the key evolutionary routes from the research corpus. The development, limitations, and opportunities of each cluster are examined, and it becomes evident that the focus of research ranges from geothermal evaluation, long-term effects of borehole heat exchangers, shallow systems that employ urbanisation's ground heating, enhanced geothermal systems (EGS) for district heating, combined and hybridised geothermal power generating models, including multi-generation and poly-generation, geothermal fluids, reinjection and their dual nature, environmental effects in geothermal water and mineral scaling, enhanced geothermal systems aiming to increase permeability without causing seismicity, and finally to social acceptability. We address significant questions, such as whether the waste heat is compatible with the idea of green geothermal heat and the elimination of pollutants and find that further R&D and technological advancements are required for this ubiquitous clean energy to get wider acceptance and employment. The future of this energy depends on the rational and scientifically sound exploration and use of the resources, just as in the case of fossil fuels, and thus precludes geothermal energy as a win-all solution to the energy needs of the whole world

Investigations on human dentine as a functionally adaptive material

This thesis details the development of experimental techniques for dental applications, aimed at understanding the "whole field" biomechanical responses underlying dento-osseous structures.Doctor of Philosophy (MPE

Antibiofilm and Immune Response of Engineered Bioactive Nanoparticles for Endodontic Disinfection

The biological aim of root canal treatment is to facilitate periapical tissue healing following endodontic therapy. This study aimed to develop an organotypic infected root canal model to understand the interaction of bacterial biofilm with macrophages and study the therapeutic effect of engineered bioactive chitosan nanoparticles (CSnp) on macrophages. Ex-vivo experiments were conducted in two phases; Phase-1: Enterococcus faecalis biofilms (two and six weeks old) developed in organotypic root canal model were used to characterize residual biofilm after conventional chemical treatment alone and combined with CSnp utilizing Confocal Laser Scanning Microscopy, Scanning Electron Microscopy and colony-forming units from pulverized dentin. Phase-2: The interaction of post-treatment biofilm and RAW macrophages was evaluated regarding pro/anti-inflammatory markers, cell viability and spreading at 24, 48 and 72 h. Compared to conventionally disinfected six-week-old biofilm, CSnp resulted in less viable bacteria (p < 0.01). Scanning electron micrographs demonstrated disruption of the biofilm. CSnp exhibited less residual bacterial load in pulverized dentin (p < 0.001). Macrophage interaction with CSnp-treated biofilm reduced proinflammatory markers (nitric oxide, TNF-α, IL-1β, and IL-6), increased anti-inflammatory marker (TGF-β1) and enhanced cell survival and spreading over time (p < 0.01 at 72 h). Engineered chitosan nanoparticles concurrently inactivated biofilm and altered the inflammatory response of macrophages that would promote healing

PHOTOSENSITISING COMPOSITION AND ITS USES

US20110027384A1Published Applicatio

Bioarchitectural Design of Bioactive Biopolymers: Structure–Function Paradigm for Diabetic Wound Healing

Chronic wounds such as diabetic ulcers are a major complication in diabetes caused by hyperglycemia, prolonged inflammation, high oxidative stress, and bacterial bioburden. Bioactive biopolymers have been found to have a biological response in wound tissue microenvironments and are used for developing advanced tissue engineering strategies to enhance wound healing. These biopolymers possess innate bioactivity and are biodegradable, with favourable mechanical properties. However, their bioactivity is highly dependent on their structural properties, which need to be carefully considered while developing wound healing strategies. Biopolymers such as alginate, chitosan, hyaluronic acid, and collagen have previously been used in wound healing solutions but the modulation of structural/physico-chemical properties for differential bioactivity have not been the prime focus. Factors such as molecular weight, degree of polymerization, amino acid sequences, and hierarchical structures can have a spectrum of immunomodulatory, anti-bacterial, and anti-oxidant properties that could determine the fate of the wound. The current narrative review addresses the structure–function relationship in bioactive biopolymers for promoting healing in chronic wounds with emphasis on diabetic ulcers. This review highlights the need for characterization of the biopolymers under research while designing biomaterials to maximize the inherent bioactive potency for better tissue regeneration outcomes, especially in the context of diabetic ulcers

Fiber optic backscatter spectroscopic sensor to monitor enamel demineralization and remineralization in vitro

In this study, a Fiber Optic Backscatter Spectroscopic Sensor (FOBSS) is used to monitor demineralization and remineralization induced changes in the enamel. A bifurcated fiber optic backscatter probe connected to a visible light source and a high resolution spectrophotometer was used to acquire the backscatter light spectrum from the tooth surface. The experiments were conducted in two parts. In Part 1, experiments were carried out using fiber optic backscatter spectroscopy on (1) sound enamel and dentine sections and (2) sound tooth specimens subjected to demineralization and remineralization. In Part 2, polarization microscopy was conducted to examine the depth of demineralization in tooth specimens. The enamel and dentine specimens from the Part-1 experiments showed distinct backscatter spectra. The spectrum obtained from the enamel-dentine combination and the spectrum generated from the average of the enamel and dentine spectral values were closely similar and showed characteristics of dentine. The experiments in Part 2 showed that demineralization and remineralization processes induced a linear decrease and linear increase in the backscatter light intensity respectively. A negative correlation between the decrease in the backscatter light intensity during demineralization and the depth of demineralization determined using the polarization microscopy was calculated to be p = -0.994. This in vitro experiment highlights the potential benefit of using FOBSS to detect demineralization and remineralization of enamel