Osteoporosis pseudoglioma syndrome (OPPG) is a rare genetic disease that produces debilitating effects in the skeleton. OPPG is caused by mutations in LRP5, a WNT co-receptor that mediates osteoblast activity. WNT signaling through LRP5, and also through the closely related receptor LRP6, is inhibited by the protein sclerostin (SOST). It is unclear whether OPPG patients might benefit from the anabolic action of sclerostin neutralization therapy (an approach currently being pursued in clinical trials for postmenopausal osteoporosis) in light of their LRP5 deficiency and consequent osteoblast impairment. To assess whether loss of sclerostin is anabolic in OPPG, we measured bone properties in a mouse model of OPPG (Lrp5−/−), a mouse model of sclerosteosis (Sost−/−), and in mice with both genes knocked out (Lrp5−/−;Sost−/−). Lrp5−/−;Sost−/− mice have larger, denser, and stronger bones than do Lrp5−/− mice, indicating that SOST deficiency can improve bone properties via pathways that do not require LRP5. Next, we determined whether the anabolic effects of sclerostin depletion in Lrp5−/− mice are retained in adult mice by treating 17-week-old Lrp5−/− mice with a sclerostin antibody for 3 weeks. Lrp5+/+ and Lrp5−/− mice each exhibited osteoanabolic responses to antibody therapy, as indicated by increased bone mineral density, content, and formation rates. Collectively, our data show that inhibiting sclerostin can improve bone mass whether LRP5 is present or not. In the absence of LRP5, the anabolic effects of SOST depletion can occur via other receptors (such as LRP4/6). Regardless of the mechanism, our results suggest that humans with OPPG might benefit from sclerostin neutralization therapies.
Nanoporous iron (hydr)oxide electrodes are evaluated as phosphate sensors using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The intensity of the reduction peak current (I cp ) of the ferrihydrite working electrode is tied to phosphate concentration at low pH; however, a hematite electrode combined with the use of EIS provided reliable sensing data at multiple pH values. Nanoporous hematite working electrodes produced an impedance phase component (q) that shifts with increasing phosphate, and, at chosen frequencies, q values were fitted for the range 1 nM to 0.1 mM phosphate at pH 4 and pH 7 in 5 mM NaClO 4 .
Nanoporous hematite (α-Fe2O3) coated electrodes were applied for the investigation of the electrochemical effects of pH on adsorption of the phosphate ion to iron oxide in concentrations commonly found in natural waters. The hematite electrode was tested with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods in NaClO4 solution and in 10−8 – 10−4 M phosphate over the pH range 6.00 – 8.75. In cyclic voltammograms, the current features attributed to specific adsorption of H+ or OH− were accentuated by phosphate addition. Impedance studies indicated that hematite behaved like a blocking electrode with deviations to blocking behavior occurring at higher pH and with increased phosphate. Resultant spectra were modeled with an analog electric circuit with a resistor in series with three parallel lines consisting of resistive, capacitive, and constant phase elements (CPEs) highlighting processes over sections of the applied EIS frequency range. This analysis of the phosphate-hematite system may assist with the production of an electrochemical sensor for phosphate at environmentally relevant pH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.