Wnt/β-catenin signaling is a critical regulator of skeletal physiology. However, previous studies have mainly focused on its roles in osteoblasts, while its specific function in osteoclasts is unknown. This is a clinically important question because neutralizing antibodies against Wnt antagonists are promising new drugs for bone diseases. Here, we show that in osteoclastogenesis, β-catenin is induced during the macrophage colony-stimulating factor (M-CSF)-mediated quiescence-to-proliferation switch but suppressed during the RANKL-mediated proliferation-to-differentiation switch. Genetically, β-catenin deletion blocks osteoclast precursor proliferation, while β-catenin constitutive activation sustains proliferation but prevents osteoclast differentiation, both causing osteopetrosis. In contrast, β-catenin heterozygosity enhances osteoclast differentiation, causing osteoporosis. Biochemically, Wnt activation attenuates whereas Wnt inhibition stimulates osteoclastogenesis. Mechanistically, β-catenin activation increases GATA2/Evi1 expression but abolishes RANKL-induced c-Jun phosphorylation. Therefore, β-catenin exerts a pivotal biphasic and dosage-dependent regulation of osteoclastogenesis. Importantly, these findings suggest that Wnt activation is a more effective treatment for skeletal fragility than previously recognized that confers dual anabolic and anti-catabolic benefits.
Hedgehog (Hh) and Bone Morphogenetic Proteins (BMPs) pattern the developing wing by functioning as short- and long-range morphogens, respectively. Here, we show that a previously unknown Hh-dependent mechanism fine-tunes the activity of BMPs. Through genome-wide expression profiling of the wing imaginal discs, we identify as a novel target gene of the Hh signaling pathway.
Prussian blue nanoparticles (PBN) exhibit selective fluorescence quenching behavior with heavy metal ions; in addition, they possess characteristic oxidant properties both for liquid-liquid and liquid-solid interface catalysis. Here, we propose to study the detection and efficient removal of toxic arsenic(III) species by materializing these dual functions of PBN. A sophisticated PBN-sensitized fluorometric switching system for dosage-dependent detection of As along with PBN-integrated SiO platforms as a column adsorbent for biphasic oxidation and elimination of As have been developed.
Rapamycins are immunosuppressant and anti-cancer drugs that inhibit the kinase mTOR. Clinically, they often cause bone pain, bone necrosis, and high bone turnover, yet the mechanisms are unclear. Here we show that mTORC1 activity is high in osteoclast precursors but downregulated upon RANKL treatment.
Wnt/β-catenin signaling is a critical regulator of skeletal physiology. However, previous studies have mainly focused on its roles in osteoblasts, while its specific function in osteoclasts is unknown. This is a clinically important question because neutralizing antibodies against Wnt antagonists are promising new drugs for bone diseases.
Effects of hCG, ovariectomy and estradiol replacement on brain, plasma and/or ovarian vasotocin in vivo, and estradiol, progesterone, 17alpha, 20beta-hydroxy-4-pregnen-3-one and hCG on ovarian vasotocin in vitro were investigated in the catfish. A 100IU/fish of hCG induced ovulation and elicited both periovulatory and post-ovulatory changes in vasotocin concentrations with a significant increase up to 8h in the brain and up to 16h in both plasma and ovary. After stripping the fish at 16h, the peptide concentration decreased significantly with time, up to 4 days.
