Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gαs/PKA and the Gαq/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gαq/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gαq/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gαq/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gαq/11 KO mice had similar bone morphology compared to WT, while CKD Gαq/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gαq/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gαq/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gαq/11/PKC KO further aggravates mineral bone disease.

A series of four multimodal ligands incorporating one porphyrin moiety and one or more dota‐like macrocycles all‐in‐one in the same molecular architecture have been synthesized and full characterized. The corresponding gadolinium(III) complexes were also synthesized and heterometallic complexes incorporating both gadolinium(III) and copper(II) ions were prepared as potential MRI/PET multimodal contrast agents. One ligand (L4) includes an amine moiety that can be activated for easy conversion into an isothiocyanate group for further anchoring to a biological vector. Preliminary relaxivity, cytotoxicity, and MRI studies showed that the complexes developed in this work are very promising medical‐imaging agents for the enhancement of contrast in bimodal MRI techniques.

Objective While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast‐like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicerd/d). Methods The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription–polymerase chain reaction (qRT‐PCR). MicroRNA macroarray profiling was monitored by qRT‐PCR. Cytokines were quantified by enzyme‐linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme‐linked immunosorbent assay. Results We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin‐6 secretion upon stimulation. Experimental serum‐transfer arthritis in Dicerd/d mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicerd/d mice exhibited increased resistance to apoptotic stimuli. Conclusion The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.

In this work, we intended to assess the reliability of guided endodontic technique to remove a bonded fibre-post when there are artefacts in the conebeam computed tomography (CBCT) images caused by composite dental materials. We mounted natural posterior teeth on ten simulated models. Forty fibre-post and composite-core restorations were inserted in the teeth. We merged a pre-operative CBCT and optical surface scan on the Blueskyplan TM software to digitally design and subsequently 3D-printed the guides. Two operators initiated endodontic access into the fibre-post restorations using the template to guide the drill. Post-operative CBCT was taken and merged onto the pre-operative plan to measure the deviations at the coronal and apical segments. The mean deviation between the planned and actual drill paths were, respectively, of 0.39 AE 0.14 mm coronally and 0.40 AE 0.19 mm apically. Microguided endodontics is a predictable and accurate method to remove fibre-post restorations efficiently.

For limited oral and maxillofacial volume imaging (diameter < 50 mm), the polyvalent small FOV CBCT (2D and three-dimensional imaging) system used in this study could reach performances similar to those of the large FOV CBCT.