Genetic regulatory mechanisms in human osteoclasts suggest a role for the STMP1 and DCSTAMP genes in Paget's disease of bone
SCIENTIFIC REPORTS
Authors: Mullin, Benjamin H.; Zhu, Kun; Brown, Suzanne J.; Mullin, Shelby; Tickner, Jennifer; Pavlos, Nathan J.; Dudbridge, Frank; Xu, Jiake; Walsh, John P.; Wilson, Scott G.
Abstract
Paget's disease of bone (PDB) is characterised by focal abnormalities of bone remodelling, with increased osteoclastic resorption the primary feature of the disease. Genetic factors have been shown to play an important role in PDB, and genome-wide association studies (GWAS) have identified 7 genetic loci as associated with PDB at the genome-wide level. Expression quantitative trait locus (eQTL) studies using cell types that are directly relevant to the disease of interest are increasingly being used to identify putative effector genes for GWAS loci. We have recently constructed a unique osteoclast-specific eQTL resource using cells differentiated in vitro from 158 subjects for study of the genetics of bone disease. Considering the major role osteoclasts have in PDB, we used this resource to investigate potential genetic regulatory effects for the 7 PDB genome-wide significant loci on genes located within 500 kb of each locus. After correction for multiple testing, we observed statistically significant associations for rs4294134 with expression of the gene STMP1, and rs2458413 with expression of the genes DPYS and DCSTAMP. The eQTL associations observed for rs4294134 with STMP1, and rs2458413 with DCSTAMP were further supported by eQTL data from other tissue types. The product of the STMP1 gene has not been extensively studied, however the DCSTAMP gene has an established role in osteoclast differentiation and the associations seen between rs2458413 and PDB are likely mediated through regulatory effects on this gene. This study highlights the value of eQTL data in determining which genes are relevant to GWAS loci.
Crystal Structures and Phosphorescent Properties of Group 14 Dipyridinometalloles and Their Copper Complexes
CHEMPLUSCHEM
Authors: Ohshita, Joji; Yamaji, Kosuke; Adachi, Yohei
Abstract
We recently reported dipyridinosilole (DPyS) and dipyridinogermole (DPyG) as pi-conjugated units that show low-temperature phosphorescence. A copper complex of DPG shows solid-state phosphorescence at room temperature. In this work, we prepared diphenyldipyridinostannole (DPySn1). Its optical and electrochemical properties were investigated and compared with those of DPyS1 and DPyG1 with the same phenyl substituents. DPySn1 showed the most red-shifted phosphorescence at 520 nm at 77 K in the solid-state, which is likely due to the intermolecular Sn-pyridine interaction that was confirmed by single-crystal X-ray diffraction. Copper complexes of DPyS1 and DPySn1 were also prepared and it was found that the phosphorescence of these dipyridinometallole-copper complex solids was red-shifted in the order of DPySn1-Cu (617 nm)