WNT5B drives osteosarcoma stemness, chemoresistance and metastasis.

Background: Treatment for osteosarcoma, a paediatric bone cancer with no therapeutic advances in over three decades, is limited by a lack of targeted therapies. Osteosarcoma frequently metastasises to the lungs, and only 20% of patients survive 5 years after the diagnosis of metastatic disease. We found that WNT5B is the most abundant WNT expressed in osteosarcoma tumours and its expression correlates with metastasis, histologic subtype and reduced survival.

Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a significant pregnancy complication linked to perinatal complications and an elevated risk of future metabolic disorders for both mothers and their children. GDM is diagnosed when women without prior diabetes develop chronic hyperglycemia due to β-cell dysfunction during gestation. Global research focuses on the association between GDM and single nucleotide polymorphisms (SNPs) and aims to enhance our understanding of GDM's pathogenesis, predict its risk, and guide patient management.

Regulation and Function of FOXC1 in Osteoblasts.

Estrogens, which bind to estrogen receptor alpha (ERα), are important for proper bone mineral density. When women go through menopause, estrogen levels decrease, and there is a decrease in bone quality, along with an increased risk for fractures. We previously identified an enhancer near as the most significantly enriched binding site for estrogen receptor alpha (ERα) in osteoblasts.

GATA4 and estrogen receptor alpha bind at SNPs rs9921222 and rs10794639 to regulate AXIN1 expression in osteoblasts.

Osteoporosis is a serious public health problem that affects 200 million people worldwide. Genome-wide association studies have revealed the association between several single nucleotide polymorphisms (SNPs) near WNT/β-catenin signaling genes and bone mineral density (BMD). The activation of β-catenin by WNT ligands is required for osteoblast differentiation.

Estrogen receptor alpha and NFATc1 bind to a bone mineral density-associated SNP to repress WNT5B in osteoblasts.

Genetic factors and estrogen deficiency contribute to the development of osteoporosis. The single-nucleotide polymorphism (SNP) rs2887571 is predicted from genome-wide association studies (GWASs) to associate with osteoporosis but has had an unknown mechanism. Analysis of osteoblasts from 110 different individuals who underwent joint replacement revealed that the genotype of rs2887571 correlates with WNT5B expression.

WNT5B in cellular signaling pathways.

The Wnt signaling ligand WNT5B is implicated in various developmental pathways, both in normal and pathological physiology. Most of the research on WNT5B has been associated with expression analysis and disease states, leaving the signaling pathways underexplored. Here, we review the current understandings of WNT5B's regulation of signal transduction, from receptors to downstream mediators and transcription factors.

Corrigendum: WNT5B in Physiology and Disease.

[This corrects the article DOI: 10.3389/fcell.2021.

WNT5B in Physiology and Disease.

WNT5B, a member of the WNT family of proteins that is closely related to WNT5A, is required for cell migration, cell proliferation, or cell differentiation in many cell types. WNT5B signals through the non-canonical β-catenin-independent signaling pathway and often functions as an antagonist of canonical WNT signaling. Although WNT5B has a high amino acid identity with WNT5A and is often assumed to have similar activities, WNT5B often exhibits unique expression patterns and functions.

GATA4 regulates mesenchymal stem cells via direct transcriptional regulation of the WNT signalosome.

GATA4 is a transcription factor that regulates osteoblast differentiation. However, GATA4 is expressed at a higher level in mesenchymal stem cells (MSCs) than in osteoblasts. Therefore, the role of GATA4 in limb bud mesenchyme differentiation was investigated in mice by knocking out Gata4 using Cre-recombinase controlled by the Prx1 promoter (herein called Gata4 Prx-cKO mice).

Anti-osteoporotic effects of Pueraria candollei var. mirifica on bone mineral density and histomorphometry in estrogen-deficient rats.

Although it has been clearly shown that Pueraria mirifica and its phytoestrogens can mimic estrogen in preventing bone loss, as osteoporosis is an asymptomatic disease, the therapeutic effects of P. mirifica should be acknowledged. In this study, 6-month-old female rats were ovariectomized, kept for 4 weeks to induce bone loss, divided into five groups, and treated with P.