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. Analysis of our ChIP-sequencing data revealed that SNP rs2887571 overlaps with an estrogen receptor alpha (ERα) binding site. Here we show that 17ß-estradiol (E2) suppresses WNT5B expression and further demonstrate the mechanism of ERα binding at the enhancer containing rs2887571 to suppress WNT5B expression differentially in each genotype. ERα interacts with NFATc1, which is predicted to bind directly at rs2887571. CRISPR-Cas9 and ChIP-qPCR experiments confirm differential regulation of WNT5B between each allele. Homozygous GG has a higher binding affinity for ERα than homozygous AA and results in greater suppression of WNT5B expression. Functionally, WNT5B represses alkaline phosphatase expression and activity, decreasing osteoblast differentiation and mineralization. Furthermore, WNT5B increases interleukin-6 expression and suppresses E2-induced expression of alkaline phosphatase during osteoblast differentiation. We show that WNT5B suppresses the differentiation of osteoblasts via receptor tyrosine kinase-like orphan receptor 1/2 (ROR1/2), which activates DVL2/3/RAC1/CDC42/JNK/SIN3A signaling and inhibits ß-catenin activity. Together, our data provide mechanistic insight into how ERα and NFATc1 regulate the non-coding SNP rs2887571, as well as the function of WNT5B on osteoblasts, which could provide alternative therapeutic targets for osteoporosis.

Promoting Surface Reconstruction of Low-Cost Stainless Steel Catalyst for Efficient Oxygen Evolution Reaction.

The development of cost-effective transition metal catalysts for oxygen evolution reaction (OER) is critical for the production of hydrogen fuel from water splitting. Low-cost and efficient stainless steel-based catalysts are expected to replace the scarce platinum group metals for large-scale energy applications. Here in this work, we report the conversion of commonly available inexpensive and easily accessible 434-L stainless steel (SS) into highly active and stable electrodes by corrosion and sulfuration strategies. The Nix Fe1-x S layer as a pre-catalyst and S-doped Nix Fe oxyhydroxides in situ formed on the catalyst surface are the true active species for OER. The optimized 434-L stainless steel-based electrocatalyst exhibits a low overpotential of 298 mV at 10 mA cm-2 in 1.0 M KOH with a small OER kinetics (the Tafel slope of 54.8 mV dec-1 ) and good stability. This work reveals the 434-L alloy stainless steel with Fe and Cr as the main elements can be used as qualified OER catalysts by surface modification, along with a new mentality to solve the energy and resource waste problems.

Constructing Hierarchical Porous MoO2 @Mo2 N@C Composite via a Confined Pyrolysis Synthetic Strategy Towards Lithium-Ion Battery Anodes.

Molybdenum dioxide (MoO2 ) demonstrates a big potential toward lithium-ion storage due to its high theoretical capacity. The sluggish reaction kinetics and large volume change during cycling process, however, unavoidably lead to inferior electrochemical performance, thus failing to satisfy the requirements of practical applications. Herein, we developed a molybdenum-based oxyacid salt confined pyrolysis strategy to achieve a novel hierarchical porous MoO2 @Mo2 N@C composite. A two-step successive annealing process was proposed to obtain a hybrid phase of MoO2 and Mo2 N, which was used to further improve the electrochemical performance of MoO2 -based anode. We demonstrate that the well-dispersed MoO2 nanoparticles can ensure ample active sites exposure to the electrolyte, while conductive Mo2 N quantum dots afford pseudo-capacitive response, which conduces to the migration of ions and electrons. Additionally, the interior voids could provide buffer spaces to surmount the effect of volume change, thereby avoiding the fracture of MoO2 nanoparticles. Benefiting from the aforesaid synergies, the as-obtained MoO2 @Mo2 N@C electrode demonstrates a striking initial discharge capacity (1760.0 mAh g-1 at 0.1 A g-1 ) and decent long-term cycling stability (652.5 mAh g-1 at 1.0 A g-1 ). This work provides a new way for the construction of advanced anode materials for lithium-ion batteries.

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/ß-catenin signaling genes and bone mineral density (BMD). The activation of ß-catenin by WNT ligands is required for osteoblast differentiation. SNP rs9921222 is an intronic variant of AXIN1 (a scaffold protein in the destruction complex that regulates ß-catenin signaling) that correlates with BMD. However, the biological mechanism of SNP rs9921222 has never been reported. Here, we show that the genotype of SNP rs9921222 correlates with the expression of AXIN1 in human osteoblasts. RNA and genomic DNA were analyzed from primary osteoblasts from 111 different individuals. Homozygous TT at rs9921222 correlates with a higher expression of AXIN1 than homozygous CC. Regional association analysis showed that rs9921222 is in high linkage disequilibrium (LD) with SNP rs10794639. In silico transcription factor analysis predicted that rs9921222 is within a GATA4 motif and rs10794639 is adjacent to an estrogen receptor alpha (ERα) motif. Mechanistically, GATA4 and ERα bind at SNPs rs9921222 and rs10794639 as detected by ChIP-qPCR. Luciferase assays demonstrate that rs9921222 is the causal SNP to alter ERα and GATA4 binding. GATA4 promoted the expression, and in contrast, ERα suppressed the expression of AXIN1 via the histone deacetylase complex member SIN3A. Functionally, the level of AXIN1 negatively correlates with the level of transcriptionally active ß-catenin. In summary, we have discovered a molecular mechanism of the SNP rs9921222 to regulate AXIN1 through GATA4 and ERα binding in human osteoblasts.

Material Nanoarchitectonics of Functional Polymers and Inorganic Nanomaterials for Smart Supercapacitors.

Smart supercapacitors are a promising energy storage solution due to their high power density, long cycle life, and low-maintenance requirements. Functional polymers (FPs) and inorganic nanomaterials are used in smart supercapacitors because of the favorable mechanical properties (flexibility and stretchability) of FPs and the energy storage properties of inorganic materials. The complementary properties of these materials facilitate commercial applications of smart supercapacitors in flexible smart wearables, displays, and self-generation, as well as energy storage. Here, an overview of strategies for the development of suitable materials for smart supercapacitors is presented, based on recent literature reports. A range of synthetic techniques are discussed and it is concluded that a combination of organic and inorganic hybrid materials is the best option for realizing smart supercapacitors. This perspective facilitates new strategies for the synthesis of hybrid materials, and the development of material technologies for smart energy storage applications.

Enhanced Hydrogen Evolution Reaction over Co Nanoparticles Embedded N-Doped Carbon Nanotubes Electrocatalyst with Zn as an Accelerant.

The rational design for transition metals-based carbon nano-materials as efficient electrocatalysts still remains a crucial challenge for economical electrochemical hydrogen production. Carbon nanotubes (CNTs) as attractive electrocatalysts are typically activated by non-metal dopant to promote catalytic performance. Metals doping or metal/non-metal co-doping of CNTs, however, are rarely explored. Herein, this work rationally designs bimetal oxide templates of ZnCo2 O4 for heterogeneously doping Zn and N into Co nanoparticles embedded carbon nanotubes (Co@Zn-N-CNTs). During the formation of CNTs, Zn atoms volatilize from ZnCo2 O4 and in situ dope into the carbon skeleton. In particular, owing to the low electronegativity of Zn, the electrons aptly transfer from Zn to carbon atoms, which generate a high electron density for the carbon layers and offer more preponderant catalytic sites for hydrogen reduction. The Co@Zn-N-CNTs catalyst exhibits enhanced hydrogen evolution reaction activity in 0.5 m H2 SO4 electrolyte, with a low onset potential of -20 mV versus RHE at 1 mA cm-2 , an overpotential of 67 mV at 10 mA cm-2 , a small Tafel slope of 52.1 mV dec-1 , and persistent long-term stability. This study provides brand-new insights into the utilization of Zn as electronic regulator and activity promoter toward the design of high-efficiency electrocatalysts.

Novel WS2 /Fe0.95 S1.05 Hierarchical Nanosphere as a Highly Efficient Electrocatalyst for Hydrogen Evolution Reaction.

Fe0.95 S1.05 with high reactivity and stability was incorporated into WS2 nanosheets via a one-step solvothermal method for the first time. The resulted hybrid catalyst has much higher catalytic activity than WS2 and Fe0.95 S1.05 alone, and the optimal WS2 /Fe0.95 S1.05 hybrid catalyst was found by adjusting the feed ratio. The addition of Fe0.95 S1.05 was proven to be able to enhance the hydrogen evolution reaction (HER) activity of WS2 , and vice versa. At the same time, it was found that the catalytic effect of the hybrid catalyst was the best when the feed ratio was W : Fe=2 : 1. In other words, we confirmed that there is a synergistic effect between W- and Fe-based sulfide hybrid catalysts, and validated that the reason for the improved HER performance is the strong interaction between the two in the middle sulfur. WS2 /Fe0.95 S1.05 -2 hybrid catalyst leads to enhanced HER activity, which shows a low overpotential of ∼0.172 V at 10 mA cm-2 , low Tafel slope of ∼53.47 mV/decade. This study supplies innovative synthesis of a highly active WS2 /Fe0.95 S1.05 hybrid catalyst for HER.

Interleukin-1 and Interleukin-6 Polymorphisms Might Influence Predisposition to Hemorrhagic Cerebral Vascular Diseases: A Meta-Analysis.

BACKGROUND: Interleukin-1 (IL-1) and IL-6 polymorphisms might influence predisposition to hemorrhagic cerebral vascular diseases, but the results of already published studies regarding relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases were still controversial and ambiguous. OBJECTIVES: The authors designed this meta-analysis to more precisely estimate the relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases by pooling the results of already published related studies. METHODS: The authors searched PubMed, EMBASE, Web of Science, and CNKI for already published studies. Eighteen already published studies were pooled analyzed in this meta-analysis. RESULTS: The pooled meta-analyses' results showed that distributions of IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms among patients and controls differed significantly. Moreover, distribution of the IL-6 rs1800795 polymorphism among patients and controls from Asians also differed significantly. Further analyses showed similar findings for IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms in aneurysmal subarachnoid hemorrhage (aSAH) subgroup. CONCLUSIONS: This meta-analysis suggested that IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms might influence susceptibility to hemorrhagic cerebral vascular diseases, especially for aSAH. Moreover, IL-6 rs1800795 might influence susceptibility to hemorrhagic cerebral vascular diseases in Asians.

Hierarchical Tubular Architecture Constructed by Vertically Aligned CoS2 -MoS2 Nanosheets for Hydrogen Evolution Electrocatalysis.

Developing efficient electrocatalysts for the hydrogen evolution reaction (HER) is crucial for establishing a sustainable and environmentally friendly energy system, but it is still a challenging issue. Herein, hierarchical tubular-structured CoS2 -MoS2 /C as efficient electrocatalysts are fabricated through a unique metal-organic framework (MOF) mediated self-sacrificial templating. Core-shell structured MoO3 @ZIF-67 nanorods are used both as a precursor and a sacrificial template to form the one-dimensional tubular heterostructure where vertically aligned two-dimensional CoS2 -MoS2 nanosheets are formed on the MOF-derived carbon tube. Trace amounts of noble metals (Pd, Rh, and Ru) are successfully introduced to enhance the electrocatalytic property of the CoS2 -MoS2 /C nanocomposites. The as-synthesized hierarchical tubular heterostructures exhibit excellent HER catalytic performance owing to the merits of the hierarchical hollow architecture with abundantly exposed edges and the uniformly dispersed active sites. Impressively, the optimal Pd-CoS2 -MoS2 /C-600 catalyst delivers a current density of 10 mA cm-2 at a low overpotential of 144 mV and a small Tafel slope of 59.9 mV/dec in 0.5 m H2 SO4 . Overall, this MOF-mediated strategy can be extended to the rational design and synthesis of other hollow heterogeneous catalysts for scalable hydrogen generation.

Practical MOF Nanoarchitectonics: New Strategies for Enhancing the Processability of MOFs for Practical Applications.

Over the past decades, the development of porous materials has directly or indirectly affected industrial production methods. Metal-organic frameworks (MOFs) as an emerging class of porous materials exhibit some unique advantages, including controllable composition, a large surface area, high porosity, and so on. These attractive characteristics of MOFs have led to their potential applications in energy storage and conversion devices, drug delivery, adsorption and storage, sensors, and other areas. However, powdered MOFs have limited practical applications owing to poor processability, safety hazards from dust formation, and poor recyclability. In addition, the inherent micro/mesoporosities of MOFs also reduce the accessibility and diffusion kinetics for large molecules. To improve their processability for practical applications, MOFs are often deposited as MOF layers or films (i.e., MOF-coated composites) on supporting materials or are formed into 3D structured composites, such as aerogels and hydrogels. In this article, we review recent researches on these MOF composites, including their synthetic methods and potential applications in energy storage devices, heavy metal ion adsorption, and water purification. Finally, the future outlook and challenges associated with the large-scale fabrication of MOF-based composites for practical applications are discussed.

Metal-Organic Frameworks and Their Derived Materials: Emerging Catalysts for a Sulfate Radicals-Based Advanced Oxidation Process in Water Purification.

With the ever-growing environmental issues, sulfate radical (SO4•- )-based advanced oxidation processes (SR-AOPs) have been attracting widespread attention due to their high selectivity and oxidative potential in water purification. Among various methods generating SO4•- , employing heterogeneous catalysts for activation of peroxymonosulfate or persulfate has been demonstrated as an effective strategy. Therefore, the future advances of SR-AOPs depend on the development of adequate catalysts with high activity and stability. Metal-organic frameworks (MOFs) with large surface area, ultrahigh porosity, and diversity of material design have been extensively used in heterogeneous catalysts, and more recently, enormous effort has been made to utilize MOFs-based materials for SR-AOPs applications. In this work, the state-of-the-art research on pristine MOFs, MOFs composites, and their derivatives, such as oxides, metal/carbon hybrids, and carbon materials for SR-AOPs, is summarized. The mechanisms, including radical and nonradical pathways, are also detailed in the discussion. This work will hopefully promote the future development of MOFs-based materials toward SR-AOPs applications.

Electrochemical Deposition: An Advanced Approach for Templated Synthesis of Nanoporous Metal Architectures.

Well-constructed porous materials take an essential role in a wide range of applications, including energy conversion and storage systems, electrocatalysis, photocatalysis, and sensing. Although the tailored design of various nanoarchitectures has made substantial progress, simpler preparation methods are compelled to meet large-scale production requirements. Recently, advanced electrochemical deposition techniques have had a significant impact in terms of precise control upon the nanoporous architecture (i.e., pore size, surface area, pore structure, etc.), enabling access to a wide range of compositions. In this Account, we showcase the uniqueness of electrochemical deposition techniques, detail their implementation toward the synthesis of novel nanoporous metals, and finally outline the future research directions. Nanoporous metallic structures are attractive in that they can provide high surface area and large pore volume, easing mass transport of reactants and providing high accessibility to catalytically active metal surface. The great merit of the electrochemical deposition approach does not only lie in its versatility, being applicable to a wide range of compositions, but also in the nanoscale precision it affords when it comes to crystal growth control, which cannot be easily achieved by other bottom-up or top-down approaches. In this Account, we describe the significant progress made in the field of nanoporous metal designed through electrochemical deposition approaches using hard templates (i.e., porous silica, 3D templates of polymer and silica colloids) and soft templates (i.e., lyotropic liquid crystals, polymeric micelles). In addition, we will point out how it accounts for precise control over the crystal growth and describe the unique physical and chemical properties emerging from these novel materials. Up to date, our group has reported the synthesis of several nanoporous metals and alloys (e.g., Cu, Ru, Rh, Pd, Pt, Au, and their corresponding alloys) under various conditions through electrochemical deposition, while investigating their various potential applications. The orientation of the channel structure, the composition, and the nanoporosity can be easily controlled by selecting the appropriate surfactants or block copolymers. The inherent properties of the final product, such as framework crystallinity, catalytic activity, and resistance to oxidation, are depending on both the composition and pore structure, which in turn require suitable electrochemical conditions. This Account is divided into three main sections: (i) a history of electrochemical deposition using hard and soft templates, (ii) a description of the important mechanisms involved in the preparation of nanoporous materials, and (iii) a conclusion and future perspectives. We believe that this Account will promote a deeper understanding of the synthesis of nanoporous metals using electrochemical deposition methods, thus enabling new pathways to control nanoporous architectures and optimize their performance toward promising applications such as catalysis, energy storage, sensors, and so forth.

Development of Sulfonic-Acid-Functionalized Mesoporous Materials: Synthesis and Catalytic Applications.

Sulfonic acid based mesostructures (SAMs) have been developed in recent years and have important catalytic applications. The primary applications of these materials are in various organic synthesis reactions, such as multicomponent reactions, carbon-carbon bond couplings, protection reactions, and Fries and Beckman rearrangements. This review aims to provide an overview of the recent developments in the field of SAMs with a particular emphasis on the reaction scope and advantages of heterogeneous solid acid catalysts.

Significant Effect of Pore Sizes on Energy Storage in Nanoporous Carbon Supercapacitors.

Mesoporous carbon can be synthesized with good control of surface area, pore-size distribution, and porous architecture. Although the relationship between porosity and supercapacitor performance is well known, there are no thorough reports that compare the performance of numerous types of carbon samples side by side. In this manuscript, we describe the performance of 13 porous carbon samples in supercapacitor devices. We suggest that there is a "critical pore size" at which guest molecules can pass through the pores effectively. In this context, the specific surface area (SSA) and pore-size distribution (PSD) are used to show the point at which the pore size crosses the threshold of critical size. These measurements provide a guide for the development of new kinds of carbon materials for supercapacitor devices.

Ni-Co Binary Hydroxide Nanotubes with Three-Dimensionally Structured Nanoflakes: Synthesis and Application as Cathode Materials for Hybrid Supercapacitors.

Nickel-cobalt binary hydroxide nanotubes were fabricated by a facile synthetic approach by using Cu2 O nanowires as sacrificial templates. The surface morphology of the binary hydroxide nanotubes can be easily controlled by adjusting the molar ratio of Ni to Co. With increasing Co content, the surfaces of the nanotubes tend to form hierarchical nanoflakes. The obtained nanotubes with high specific surface area exhibit typical battery-like electrochemical behavior. Among them, Ni-Co hydroxide nanotubes with Ni:Co=48:52 showed outstanding electrochemical characteristics, with a specific capacity of 209.9 mAh g-1 at 1 Ag-1 and remarkable cycling stability with 84.4 % capacity retention after 10 000 cycles at 20 A g-1 . With the advantages of their unique nanostructure and the synergistic effect of the two elements, the Ni-Co binary hydroxide nanotubes are expected to be effective potential cathode materials for hybrid supercapacitors.

N719- and D149-sensitized 3D hierarchical rutile TiO2 solar cells--a comparative study.

Poor dye loading on rutile TiO2 is one of the chief reasons for lower solar-to-electric conversion efficiency (η) in dye-sensitized solar cells (DSCs), compared to their anatase based counterparts. Previously, we showed that similar light harvesting for both rutile and anatase was realized by using a metal-free organic indoline dye, D149 [Sci. Rep., 2014, 4, 5769]. This was in contrast to the bulk of previous studies, which employed ruthenium based N719, leading to significant differences in light harvesting. To date, there has been no report directly comparing N719 and D149 for rutile based DSCs. In this work, three-dimensional hierarchical rutile TiO2 architecture (HRTA), consisting of one-dimensional nanorods, was successfully prepared via a facile hydrothermal method, and subsequently optimized as effective photoelectrodes for DSCs. Two dyes, N719 and D149, were used as sensitizers of the HRTA-based DSCs, with maximum η of 5.6% and 5.8% achieved, respectively. The higher η of the D149-sensitized DSC is ascribed to its higher extinction co-efficient, allowing a greater amount of light to be harvested with a thinner TiO2 layer. This study suggests that some of the limitations typically observed for rutile TiO2 based DSCs can be overcome through the use of strongly absorbing metal-free organic sensitizers. Furthermore, it reemphasises the importance of viewing DSCs as whole systems, rather than individual components.

Cerium-Doped Nickel Sulfide Nanospheres as Efficient Catalysts for Overall Water Splitting.

The development of non-precious metal electrocatalysts with excellent activity and durability for electrochemical water splitting has always been a goal. Transition metal sulfides are attractive electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). In this article, we designed and constructed efficient catalysts with multiple synergistic interactions and synthesized Ce-NiS2@NF nanosphere using a solvothermal method. Ce-NiS2@NF exhibits excellent HER performance, OER performance, and overall water splitting capability in alkaline electrolytes, demonstrating good stability. The addition of Ce influences the activity of the catalysts, attributed to the synergistic interactions creating more active sites and higher intrinsic activity through the introduction of Ce heteroatoms. Additionally, the self-supported conductive substrate promotes electron transfer, enhancing the intrinsic activity and active site density of the catalyst. This study provides an in-depth investigation into structural design and performance enhancement, offering ideas for designing efficient catalysts for overall water electrolysis. This work provides an in-depth study in terms of structural design performance enhancement and provides ideas for designing efficient alkaline bifunctional catalysts. Valuable insights have been provided in elucidating the intrinsic mechanism of the catalytic activity of cerium-doped nickel sulfide nanospheres, thus providing new guidance in the field of energy conversion technology.

Constructing WS2/WO3-x heterostructured electrocatalyst enriched with oxygen vacancies for accelerated hydrogen evolution reaction.

H2 produced through hydrogen evolution reaction (HER) is a shining star in the field of clean energy. Significant efforts have been dedicated to develop efficient and stable electrocatalysts to reduce the energy barrier and accelerate the kinetics of Hydrogen evolution reaction (HER) under various environments. Herein, we propose a strategy to accelerate the kinetics of HER under acid and alkaline environments by combining heterostructure engineering with defect engineering. We have successfully synthesized a series of WS2/WO3-x heterostructured catalysts, accompanied with substantial oxygen vacancies using a two-step synthesis method. With the partially sulfurization of WO3-x, the heterojunction interface of WS2 and WO3-x was formed along with the appearance of oxygen vacancies, which can facilitate the migration of electrons. The heterostructured catalyst enriched with oxygen vacancies (defined as WS2/WO3-x-2) demonstrates superior HER performance in acidic and alkaline electrolytes. At a current density of 10 mA cm-2, the WS2/WO3-x-2 heterostructured catalyst manifests an overpotential of 120 mV in the acidic electrolytes and a slightly higher overpotential of 150 mV in an alkaline environment. The overpotentials offer an improvement compared to reported W-based catalysts in terms of HER performance. This work provides guiding significance on the design of heterostructured catalysts with promising performance for HER in acidic and alkaline environments.

Cerium Doping-Induced Enrichment of Ni3S4 Phase for Boosting Oxygen Evolution Reaction.

The development of low-cost transition metal compounds with high-performance for efficient oxygen evolution reaction (OER) is of great significance in promoting the development of electrocatalysis. In this study, a Ce-doped Ni3S4 catalyst (Ce0.2-Ni3S4) was synthesized through a one-step solvothermal method, where the doped rare earth element Ce induced the transformation of NiS to Ni3S4. The Ce0.2-Ni3S4 catalyst exhibited excellent OER performance in 1 M KOH. At a current density of 10 mA cm-2, it showed a low overpotential of 230 mV and a low Tafel slope of 52.39 mV dec-1. Long-term OER tests at the same potential lasted for 24 h without significant loss of current density. This work introduces a novel method of Ce element doping for modifying transition metal sulfides, providing new insights into the effective utilization of rare earth elements in the field of electrochemistry. It creates more chances for the progress of highly efficient catalysts for efficient OER, contributing to the advancement of electrocatalysis.

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. METHODS: Using tumor-spheroids to model cancer stem-like cells, we performed qPCR, immunoblotting, and immunofluorescence to monitor changes in gene and protein expression. Additionally, we measured sphere size, migration and forming efficiency to monitor phenotypic changes. Therefore, we characterised WNT5B's relevance to cancer stem-like cells, metastasis, and chemoresistance and evaluated its potential as a therapeutic target. RESULTS: In osteosarcoma cell lines and patient-derived spheres, WNT5B is enriched in stem cells and induces the expression of the stemness gene SOX2. WNT5B promotes sphere size, sphere-forming efficiency, and cell proliferation, migration, and chemoresistance to methotrexate (but not cisplatin or doxorubicin) in spheres formed from conventional cell lines and patient-derived xenografts. In vivo, WNT5B increased osteosarcoma lung and liver metastasis and inhibited the glycosaminoglycan hyaluronic acid via upregulation of hyaluronidase 1 (HYAL1), leading to changes in the tumour microenvironment. Further, we identified that WNT5B mRNA and protein correlate with the receptor ROR1 in primary tumours. Targeting WNT5B through inhibition of WNT/ROR1 signalling with an antibody to ROR1 reduced stemness properties, including chemoresistance, sphere size and SOX2 expression. CONCLUSIONS: Together, these data define WNT5B's role in driving osteosarcoma cancer stem cell expansion and methotrexate resistance and provide evidence that the WNT5B pathway is a promising candidate for treating osteosarcoma patients. KEY POINTS: WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.