DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion of osteoclast precursors during osteoclast (OC) development. DC-STAMP−/− mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function but the absence of known DC-STAMP ligand has hindered examination of downstream signaling pathways. To address this problem, we engineered a light-activatable DC-STAMP chimeric molecule in which light exposure mimics ligand engagement that can be traced by downstream Ca2+ signaling. Deletion of the cytoplasmic ITIM resulted in a significant elevation in the amplitude and duration of intracellular Ca2+ flux. We also found that decreased NFATc1 expression in DC-STAMP−/− cells was restored by DC-STAMP over-expression. Multiple biological phenotypes including cell-cell fusion, bone erosion, cell mobility, DC-STAMP cell surface distribution, and NFATc1 nuclear translocation were altered by deletion of the ITIM and adjacent amino acids. In contrast, mutations on each of tyrosine residues in the ITIM showed no effect on DC-STAMP function. Collectively, our results suggest that ITIM on DC-STAMP is a functional motif that regulates osteoclast differentiation through the NFATc1 / Ca2+ axis.

Background: Urology authors are required to evaluate research achievements (RAs) in the field of bladder cancer (BC). However, no such bibliometric indices were appropriately applied to quantify the contributions to BC in research. In this study, we examined 3 questions: whether RAs in China are higher than those in the United States, how the Sankey-based temporal bar graph (STBG) may be applied to the analysis of the trend of article citations in the BC field, and what subthemes were reflected in China’s and the United States’ proportional counts in BC articles. Methods: Using the PubMed search engine to download data, we conducted citation analyses of BC articles authored by urology scholars since 2012. A total of 9885 articles were collected and analyzed using the relative citations ratios (RCRs) and the STBG. The 3 research goals were verified using the RCRs, the STBG, and medical subject headings (MesH terms). The choropleth map and the forest plot were used to 1 highlight the geographical distributions of publications and RCRs for countries/regions and 2 compare the differences in themes (denoted by major MeSH terms on proportional counts using social network analysis to cluster topics) between China and the United States. Results: There was a significant rise over the years in RCRs within the 9885 BC articles. We found that the RCRs in China were substantially higher than those in the United States since 2017, the STBG successfully explored the RCR trend of BC articles and was easier and simpler than the traditional line charts, area plots, and TBGs, and the subtheme of genetics in China has a significantly higher proportion of articles than the United States. The most productive and influential countries/regions (denoted by RCRs) were {Japan, Germany, and Italy} and {Japan, Germany, New York}, respectively, when the US states and provinces/metropolitan cities/areas in China were separately compared to other countries/regions. Conclusions: With an overall increase in publications and RCRs on BC articles, research contributions assessed by the RCRs and visualized by the STBGs are suggested for use in future bibliographical studies.

No abstract