DKK-1, human
- Known as:
- DKK-1, H. sapiens
- Catalog number:
- P705-500
- Product Quantity:
- 500 ug
- Category:
- -
- Supplier:
- 101 Bio.
- Gene target:
- DKK-1 human
Related genes to: DKK-1, human
- Gene:
- DKK1 NIH gene
- Name:
- dickkopf WNT signaling pathway inhibitor 1
- Previous symbol:
- -
- Synonyms:
- SK, DKK-1
- Chromosome:
- 10q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-01
- Date modifiied:
- 2018-06-28
Related products to: DKK-1, human
Related articles to: DKK-1, human
- ARHGEF3 (also known as XPLN) is a Rho guanine nucleotide exchange factor that activates RhoA/B. Variants in the ARHGEF3 gene are associated with hip and spine BMD and fracture risk, suggesting ARHGEF3 may play key role in maintaining bone mass. However, the extent to which ARHGEF3 facilitates the anabolic and catabolic effects of RhoA are unclear alongside the down-stream impact on bone mass. We report using knockout mice that ARHGEF3 deletion leads to significant gains in cortical area and moment of inertia, driven by increased periosteal bone formation. Increased periosteal bone formation was attributed to osteocytes' down-regulation of sclerostin and Dkk1 combined with increased Wnt3a and Wnt5a expression. In contrast, endocortical bone formation was reduced in KO mice and attributed to deficits in mineralization despite gains in osteoblast viability and alkaline phosphatase activity. ARHGEF3 deletion also suppressed bone resorption despite no direct effect on osteoclastogenesis. Instead, the decrease in osteoclast numbers and bone resorption in the absence of ARHGEF3 is attributed to decreased M-CSF levels among osteoblasts and osteoblast precursors. Collectively, our findings demonstrate that ARHGEF3 deletion has pro-anabolic and anti-catabolic effects that increase bone mass and may offer a novel target for preventing bone loss in an aging population. - Source: PubMed
Publication date: 2026/06/11
Chougule AmitZhang ChunbinDenbow JordanVinokurov NickolasGardinier Joseph - Annexin A6 (AnxA6) is a predominantly intracellular calcium-dependent membrane-binding multifunctional protein that is also detected extracellularly and in small extracellular vesicles (exosomes). We previously demonstrated that lapatinib resistance in triple-negative breast cancer (TNBC) cells is associated with AnxA6 upregulation and accumulation of cholesterol in late endosomes. Here, we investigated the fate of AnxA6 and cholesterol in lapatinib-resistant (LAP-R) cells and whether extracellular AnxA6 influences TNBC cell survival. We demonstrate that reduced expression of AnxA6 in LAP-R cells decreased the secretion of MCP-1/CCL2, CCL8/IL-8, DKK1, TSP-1, and OPN by antibody arrays. The secretion of exosomes was also markedly reduced in AnxA6-depleted LAP-R cells, while AnxA6 upregulation stimulated the release of MCP-1 and exosomes. Compared to the respective controls, exosome-associated AnxA6, Rab7, and cholesterol levels were increased in exosomes isolated from AnxA6-expressing LAP-R cells. Mechanistically, we demonstrated by co-immunoprecipitation, GST pulldown, and proximity ligation assays that AnxA6 interacts with SNAP23, a component of the membrane fusion machinery. Finally, blocking extracellular AnxA6 with neutralizing antibodies reduced the viability of AnxA6-low TNBC cells but had little effect on AnxA6-high cells. These findings suggest that extracellular AnxA6 is critical for the survival of highly proliferative AnxA6-low basal-like breast cancer cells and that AnxA6 influences TNBC progression by facilitating the secretion of pro-inflammatory cytokines and cholesterol-enriched exosomes. - Source: PubMed
Publication date: 2026/05/31
Sakwe Nobelle IKorolkova Olga YVuong Ngoc BEdwards Alayjha DBlack Perrin JBall Destiny DMcIntosh Antonisha RThomas Portia LWhalen Melvin Diva SBeasley Heather KHinton Antentor OOchieng JosiahSakwe Amos M - This study aimed to evaluate periosteum-derived mesenchymal stem cells (P-MSCs) cultured under simulated microgravity (SMG) conditions. P-MSCs were induced toward osteogenic differentiation and then exposed to SMG for up to 48 h. As a control, P-MSCs were maintained under identical conditions but without SMG exposure. Cell viability, osteogenesis-related analytes, and gene expression were analyzed at 3, 24 and 48 h. Cell viability under SMG was lower after 3 h but was significantly higher after 24 h, with no difference at 48 h. There was a higher expression of pathways associated with inflammation at 3 h, which was attenuated by 24 h and neutralized at 48 h. P-MSCs under SMG demonstrated three characteristics in at least one timepoint, which supports a pro-osteogenic signaling response: (1) higher osteoprotegerin levels; (2) lower DKK1 and TNF levels; (3) upregulation of genes related to osteogenesis. Our data suggest that P-MSCs exhibit enhanced pro-osteogenic regulatory modulation in SMG. - Source: PubMed
Publication date: 2026/05/28
Canal RaulMartinez Elizabeth FFoster Jamie SBombaldi de Souza Fernanda CarlaBombaldi de Souza Renata FrancielleMorales Marcelo MarcosPontes Marcos Cesarda Rocha Daniel NHolliday Lexie SYu FahongSilva Anderson TadeuFanganiello Roberto DFerreira José Ricardo MPelegrine André A - Type 1 diabetes is associated with increased fracture risk, yet the respective contributions of insulin deficiency and replacement to skeletal fragility remain poorly understood. Using insulin-deficient male Akita mice, we characterized skeletal alterations and assessed the effects of early insulin therapy. Untreated male Akita mice displayed severe hyperglycemia, impaired growth, low bone formation, and marked trabecular and cortical deficits, resulting in reduced whole-bone structural mechanical properties. Insulin therapy initiated at early diabetes onset normalized glycemia, restored bone formation, and fully recovered cortical material properties. However, cortical porosity remained elevated, cortical geometry was not fully restored, and whole-bone structural mechanical properties did not improve. Gene expression profiling showed downregulation of osteoblast, osteocyte, mechanosensing, and Wnt-related genes in male Akita mice. Notably, Sp7 (Osterix) and Ostn (Osteocrin), key regulators of osteocyte dendrite formation, were downregulated in male Akita mice, suggesting disrupted osteocyte network development. Insulin upregulated osteogenic and Wnt signaling targets but incompletely restored mechanosensing pathways. Importantly, expression of the Wnt inhibitors Sost (Sclerostin) and Dkk1 (Dickkopf-1) remained elevated despite insulin treatment, potentially maintaining an inhibitory environment that limits the anabolic response to mechanical loading. These findings show that early insulin therapy improves bone health in type 1 diabetes, including turnover, trabecular structure, and cortical tissue material properties, but fails to fully rescue cortical integrity and whole-bone structural mechanical properties. This incomplete recovery likely reflects persistent defects in osteocyte function and mechanosensing in insulin-deficient bone and highlights potential therapeutic targets beyond glycemic control to reduce fracture risk in type 1 diabetes. - Source: PubMed
Publication date: 2026/06/10
Toillon IndiraBadoud IsabelleFerrari SergeGerbaix Maude - Two hundred Holstein dairy cows (milk yield of 34.5 ± 0.6 kg/d, 3.1 ± 1.2 lactations) were enrolled to investigate the role of WNTs signaling network in early pregnancy loss. The ISG15 mRNA abundance of uterine luminal cells obtained via brushing on day 16 after service was used to determine initial pregnancy status, with confirmation via ultrasound on days 32 and 60. The mRNA abundance of cells obtained from uterine brushing for WNT2, WNT5A, WNT7A, WNT11, frizzled receptors (FZD), dickkopf proteins (DKK1), Kremen and LDL receptor related protein (LRP 5/6), lymphoid enhancer-binding factor 1 (LEF1) and transcription factor 7 (TCF) was determined at day16 after insemination. Relative mRNA abundance of DKK1 (1.98-fold), WNT5A (2.67-fold), WNT7A (1.83-fold) and WNT11 (2.16-fold) genes in pregnant cows were significantly greater than in cows with early embryonic mortality (P < 0.05). In contrast, relative mRNA abundance of WNT2 (3.35-fold) and FZD6 (5.50-fold) genes were significantly greater in pregnant-embryo loss cows compared to pregnant cows on day 16 (P < 0.05). The relative mRNA abundance of LRP5, LRP6, LEF1, FZD3, FZD5, FZD8 and TCF genes were not affected by pregnancy status although their variances were lower; however, there was a negative correlation among ISG15 and these genes. In conclusion, differences in mRNA abundance of WNT signaling genes in uterine brushing samples are associated with pregnancy status in lactating dairy cows and may contribute to minimizing early bovine pregnancy losses. - Source: PubMed
Publication date: 2026/06/04
Dirandeh EAnsari-Pirsaraei ZThatcher W W