更新于：2024-05-01

WNT16

Wnt family member 16

更新于：2024-05-01

基本信息

别名

Protein Wnt-16、Wnt family member 16、WNT16

简介

Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity).

关联

100 项与 WNT16 相关的临床结果

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100 项与 WNT16 相关的转化医学

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0 项与 WNT16 相关的专利（医药）

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246

项与 WNT16 相关的文献（医药）

2024-01-22·Biomedicines

Potential Interaction between WNT16 and Vitamin D on Bone Qualities in Adolescent Idiopathic Scoliosis Patients and Healthy Controls.

Article

作者: Guangpu Kenneth Yang ; Huanxiong Chen ; Ka-Lo Cheng ; Man-Fung Tang ; Yujia Wang ; Lik-Hang Alec Hung ; Chun-Yiu Jack Cheng ; King-Lun Kingston Mak ; Yuk-Wai Wayne Lee

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that is associated with low bone mineral density (BMD). Vitamin D (Vit-D) supplementation has been suggested to improve BMD in AIS, and its outcomes may be related to genetic factors. The present study aimed to (a) investigate the synergistic effect between a low BMD-related gene (wingless-related integration site 16, WNT16) and two important Vit-D pathway genes (Vit-D receptor, VDR, and Vit-D binding protein, VDBP) on serum Vit-D and bone qualities in Chinese AIS patients and healthy adolescents, and (b) to further investigate the effect of ablating Wnt16 on the cortical bone quality and whether diets with different dosages of Vit-D would further influence bone quality during the rapid growth phase in mice in the absence of Wnt16. A total of 519 girls (318 AIS vs. 201 controls) were recruited, and three selected single-nucleotide polymorphisms (SNPs) (WNT16 rs3801387, VDBP rs2282679, and VDR rs2228570) were genotyped. The serum 25(OH)Vit-D level was significantly associated with VDBP rs2282679 alleles (OR = -4.844; 95% CI, -7.521 to -2.167, p < 0.001). Significant multi-locus models were identified by generalized multifactor dimensionality reduction (GMDR) analyses on the serum 25(OH)Vit-D level (p = 0.006) and trabecular area (p = 0.044). In the gene-edited animal study, Wnt16 global knockout (KO) and wildtype (WT) male mice were provided with different Vit-D diets (control chow (1000 IU/Kg) vs. Vit-D-deficient chow (Nil in Vit-D) vs. high-dose Vit-D chow (20,000 IU/Kg)) from 4 weeks to 10 weeks old. Wnt16 global KO mice had significantly lower serum 25(OH)Vit-D levels and higher liver Vdbp mRNA expression levels than WT mice. In addition, Wnt16 global KO mice showed a decrease in bone density, cortical thickness and cortical area compared with WT mice. Interestingly, high-dose Vit-D chow led to lower bone density, cortical thickness, and cortical area in WT mice, which were less obvious in Wnt16 global KO mice. In conclusion, WNT16 may regulate the serum 25(OH)Vit-D level and bone qualities, which might be associated with VDBP expression. Further investigations with a larger sample size and wider spectrum of scoliosis severity are required to validate our findings regarding the interaction between WNT16 and Vit-D status in patients with AIS.

2023-12-20·Endocrinology

Wnt16 Promotes Vascular Smooth Muscle Contractile Phenotype and Function via Taz(Wwtr1) Activation in Male LDLR-/- Mice.

Article

作者: Abraham Behrmann ; Dalian Zhong ; Li Li ; Shangkui Xie ; Megan Mead ; Parastoo Sabaeifard ; Mohammad Goodarzi ; Andrew Lemoff ; Julia Kozlitina ; Dwight A Towler

Wnt16 is expressed in bone and arteries, and maintains bone mass in mice and humans, but its role in cardiovascular physiology is unknown. We show that Wnt16 protein accumulates in murine and human vascular smooth muscle (VSM). WNT16 genotypes that convey risk for bone frailty also convey risk for cardiovascular events in Dallas Heart Study. Murine Wnt16 deficiency, which causes postnatal bone loss, also reduced systolic blood pressure. Electron microscopy demonstrated abnormal VSM mitochondrial morphology in Wnt16-null mice, with reductions in mitochondrial respiration. Following angiotensin-II (AngII) infusion, thoracic ascending aorta (TAA) dilatation was greater in Wnt16-/- vs. Wnt16+/+ mice (LDLR-/- background). Acta2 deficiency has been shown to impair contractile phenotype and worsen TAA aneurysm with concomitant reductions in blood pressure. Wnt16 deficiency reduced expression of Acta2, SM22, and other contractile genes, and reduced VSM contraction induced by TGFβ. Acta2 and SM22 proteins were reduced in Wnt16-/- VSM as was Ankrd1, a prototypic contractile target of Yap1 and Taz activation via TEAD-directed transcription. Wnt16-/- VSM exhibited reduced nuclear Taz and Yap1 protein accumulation. SiRNA targeting Wnt16 or Taz, but not Yap1, phenocopied Wnt16 deficiency, and Taz siRNA inhibited contractile gene upregulation by Wnt16. Wnt16 incubation stimulated mitochondrial respiration and contraction (reversed by verteporfin, a Yap/Taz inhibitor). SiRNA targeting Taz inhibitors Ccm2 and Lats1/2 mimicked Wnt16 treatment. Wnt16 stimulated Taz binding to Acta2 chromatin and H3K4me3 methylation.. TEAD cognates in the Acta2 promoter conveyed transcriptional responses to Wnt16 and Taz. Wnt16 regulates cardiovascular physiology and VSM contractile phenotype, mediated via Taz signaling.

2023-11-17·bioRxiv : the preprint server for biology

A framework for defining mesenchymal cell types associated with murine periosteal and endosteal bone.

作者: Intawat Nookaew ; Jinhu Xiong ; Melda Onal ; Cecile Bustamante-Gomez ; Visanu Wanchai ; Qiang Fu ; Ha-Neui Kim ; Maria Almeida ; Charles A O'Brien

Single-cell RNA sequencing has led to numerous novel designations for mesenchymal cell types associated with bone. Consequently, there are now multiple designations for what appear to be the same cell type. In addition, existing datasets contain relatively small numbers of mature osteoblasts and osteocytes and there has been no comparison of periosteal bone cells to those at the endosteum and trabecular bone. The main goals of this study were to increase the amount of single cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types associated with murine bone. To do this, we created an atlas of murine bone-associated cells by harmonizing published datasets with in-house data from cells targeted by Osx1-Cre and Dmp1-Cre driver strains. Cells from periosteal bone were analyzed separately from those isolated from the endosteum and trabecular bone. Over 100,000 mesenchymal cells were mapped to reveal 11 major clusters designated fibro-1, fibro-2, chondrocytes, articular chondrocytes, tenocytes, adipo-CAR, osteo-CAR, pre-osteoblasts, osteoblasts, osteocytes, and osteo-X, the latter defined in part by Postn expression. Osteo-X, osteo-CAR, and pre-osteoblasts were closely associated with osteoblasts at the trabecular bone surface. Wnt16 was expressed in multiple cell types from the periosteum but not in any cells from endocortical or cancellous bone. Fibro-2 cells, which express markers of skeletal stem cells, localized to the periosteum but not trabecular bone in adult mice. Suppressing bone remodeling eliminated osteoblasts and altered gene expression in pre-osteoblasts but did not change the abundance or location of osteo-X or osteo-CAR cells. These results provide a framework for identifying bone cell types in murine single cell RNA sequencing datasets and suggest that osteoblast progenitors reside near the surface of remodeling bone.

Author Summary:

The skeleton of vertebrate animals is produced by bone forming cells known as osteoblasts. New osteoblasts are continually produced throughout life to maintain the skeleton. However, the identity of the cells from which new osteoblasts are derived is not clear. Single cell RNA sequencing provides a gene expression profile of individual cells and allows them to be grouped into clusters of cells with similar profiles. In many cases, distinct clusters represent distinct cell types. Recent single cell RNA sequencing studies of mouse bones by several different laboratories have identified many novel cell types, some of which may be osteoblast progenitors. In many cases, different laboratories have created different names for what appear to be the same cell type. To help clarify this situation, we performed single cell RNA sequencing studies and combined our results with those from several published studies to create a harmonized map of the cell types associated with mouse bones. We also identified gene signatures for each cell type that can be used to improve the consistency of cell type designation in future single cell RNA sequencing studies of mouse bone.

项与 WNT16 相关的新闻（医药）

2024-01-08

·GlobeNewswire-Health Care

Altamira Therapeutics to Present at 3rd Annual mRNA-Based Therapeutics Summit

HAMILTON, BERMUDA , Jan. 08, 2024 (GLOBE NEWSWIRE) -- Altamira Therapeutics to Present at 3rd Annual mRNA-Based Therapeutics Summit Altamira’s two flagship programs, AM-401 and AM-411, designed for KRAS-driven cancer and rheumatoid arthritis, serve to demonstrate the technology’s capability to enhance therapeutic efficacy HAMILTON, BERMUDA Jan. 8, 2023 (GLOBE NEWSWIRE) -- Altamira Therapeutics Ltd. ("Altamira" or the "Company") (Nasdaq: CYTO), a company providing nanoparticle-based technology for efficient RNA delivery to extrahepatic targets, announced today that it will be presenting at the 3rd Annual mRNA-Based Therapeutics Summit, being held January 23-25 at the JW Marriott Hotel, Berlin. Covadonga Pañeda, Ph.D., the Company's Chief Operating Officer, will give a presentation at the conference titled, "Delivery of therapeutic RNA in inflammation and cancer using peptide-based nanoparticles”. In addition, she will participate in the panel discussion on “Tissue specific targeting of mRNA to increase therapeutic efficacy.” "There is a strong and growing interest in the use of mRNA for highly targeted treatment of a broad range of human diseases, based on the unique ability of mRNA to promote expression of specific proteins,” Dr. Pañeda commented. “However, even the most powerful mRNA therapeutic is useless if it is not delivered safely and effectively into target cells, which has remained one of the key challenges for non-hepatic targets to date. Thanks to our SemaPhore platform we are able to deliver therapeutic mRNA, in an efficient and safe manner, to tissues harboring a tumor or suffering from acute or chronic inflammation, restricting the therapeutic effect of the drug to the site where it is needed." SemaPhore™, Altamira’s peptide-based delivery platform for mRNA, has been successfully tested so far in vivo in models of osteoarthritis (WNT16, DNMT3B), atherosclerosis (p27Kip1), aortic aneurysm (SOD2), and tumor microenvironment (ZBTB46). About Altamira Therapeutics Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a 49% stake (with additional economic rights) in its commercial-stage legacy asset Bentrio®, an OTC nasal spray for allergic rhinitis. Further, the Company is in the process of partnering / divesting its inner ear legacy assets (AM-125 nasal spray for vertigo; post Phase 2; Keyzilen® and Sonsuvi® for tinnitus and hearing loss; Phase 3). Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com Forward-Looking Statements This press release may contain statements that constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Altamira’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as "may", "might", "will", "should", "expects", "plans", "anticipates", "believes", "estimates", "predicts", "projects", "potential", "outlook" or "continue", or the negative of these terms or other comparable terminology. Forward-looking statements are based on management's current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the success of strategic transactions, including licensing or partnering, with respect to Altamira’s legacy assets, Altamira’s need for and ability to raise substantial additional funding to continue the development of its product candidates, the clinical utility of Altamira’s product candidates, the timing or likelihood of regulatory filings and approvals, Altamira’s intellectual property position and Altamira’s financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Altamira’s capital structure, including future securities offerings. These risks and uncertainties also include, but are not limited to, those described under the caption "Risk Factors" in Altamira’s Annual Report on Form 20-F for the year ended December 31, 2022, and in Altamira’s other filings with the Securities Exchange Commission (“SEC”), which are available free of charge on the SEC’s website at: www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Altamira or to persons acting on behalf of Altamira are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Altamira does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law.

临床2期临床3期siRNA寡核苷酸信使RNA

2023-05-29

·生物谷

这个lncRNA突变让她感觉不到疼痛、焦虑和恐惧，背后的机制是什么？

研究团队发现，FAAH-OUT能够调控FAAH的表达，导致FAAH的酶活性水平显著降低。除了导致感觉不到疼痛以外，该研究还确定了其影响伤口愈合和情绪的分子途径，这些途径都受到FAAH-OUT的影响。图中这位名叫乔·卡梅伦（Jo Cameron）的女士，拥有一个不可思议的“超能力”，她的一生中经历过骨折、手术和分娩，但她却感觉不到这些疼痛，甚至完全不需要止痛药，而且，她还不会感觉到焦虑、恐惧和不适。 2013年，乔被诊断出患有严重的髋关节退行性变，一年后她接受了手术，令医生惊讶的是，她在术前和术后都没有感觉到疼痛。此时她才意识到自己的与众不同。近日，伦敦大学学院（UCL）的研究人员在 Brain 期刊发表了题为：Molecular basis of FAAH-OUT-associated human pain insensitivity 的研究论文。该研究揭示了乔·卡梅伦（Jo Cameron）携带的一种 lncRNA FAAH-OUT 的基因突变导致其几乎没有疼痛感、伤口愈合更快，而且不会感到焦虑和恐惧的生物学基础。揭开这种罕见基因突变背后的机制，为开发更有效的止痛药带来了新希望。生活在苏格兰的乔·卡梅伦（Jo Cameron）在一次大手术中被医生注意到没有疼痛感，于是她被推荐给了伦敦大学学院的疼痛遗传学家。经过6年的寻找，发现乔携带了一种lncRNA FAAH-OUT 的罕见突变，是导致她如此与众不同的原因。研究团队发现的乔的基因组中含有FAAH-OUT的区域，实际上是以前被认为没有功能的“垃圾DNA”，转录成为一段长链非编码RNA（lncRNA），而这项研究显示，它可以调控FAAH（脂肪酸酰胺水解酶）的表达，而FAAH是内源性大麻素（endocannabinoid，eCB）系统的一部分，在内源性大麻素的代谢中发挥关键作用，与疼痛、情绪和记忆有关。具体来说，FAAH-OUT lncRNA转录的中断，会导致FAAH启动子内DNMT1依赖性的DNA甲基化。此外，FAAH-OUT还包含一个保守的调控元件FAAH-AMP，它作为FAAH表达的增强子。因此，FAAH-OUT的突变导致了FAAH表达的显著下调。研究团队进一步尝试解析FAAH-OUT在分子水平上是如何工作的，这是能够利用这种独特的生物学原理进行药物开发等应用的第一步。研究团队在细胞水平上进行CRISPR-Cas9基因编辑实验，模拟这种突变对其他基因的影响，进而分析基因的表达，看看哪些基因在与疼痛、情绪和愈合有关的分子途径中是活跃的。研究团队发现，FAAH-OUT能够调控FAAH的表达，导致FAAH的酶活性水平显著降低。除了导致感觉不到疼痛以外，该研究还确定了其影响伤口愈合和情绪的分子途径，这些途径都受到FAAH-OUT的影响。具体来说，研究团队对来自乔的成纤维细胞进行了研究，以探索FAAH-OUT-FAAH信号轴对其他分子通路的影响，结果显示，FAAH-OUT除了抑制FAAH以外，还有其他797个基因被激活，348个基因被抑制。其中包括与伤口愈合相关的WNT信号通路的改变，以及与骨再生相关的WNT16基因活性的增加。其中两个被改变的关键基因是BDNF和ACKR3，前者与情绪调节有关，后者表达一种阿片受体，能够抑制阿片类药物的镇痛和抗焦虑活性。这些基因变化可能导致乔·卡梅伦感觉不到焦虑、恐惧和疼痛。论文通讯作者、伦敦大学学院的 James Cox 教授表示，最初发现乔·卡梅伦独特表现的遗传根源是一个令人兴奋的时刻，而现在这些发现真正开始变得有趣，通过精确地了解分子水平上发生的事情，我们可以开始解析其中涉及的生物学机制，为药物发现开辟了可能性，有朝一日可能对患者产生深远的积极影响。

基因疗法临床研究

2023-05-23

·drugs

Biological Secrets of the Woman Who Can't Feel Pain

WEDNESDAY, May 24, 2023 -- A unique genetic brew has benefitted a Scottish woman who lives virtually pain-free, heals more rapidly and experiences reduced anxiety and fear, researchers from University College London report. Pain geneticists have been studying the woman, Jo Cameron, for a decade. She came to their attention when her doctor noticed that she experienced no pain after major surgeries on her hip and hand. After six years of examination, researchers identified a new gene named FAAH-OUT, which contained genetic mutations that were the cause of Cameron’s unique abilities. However, they still had no idea how exactly these mutations benefitted her, so research continued, leading to this new study . The area of the genome containing FAAH-OUT had previously been assumed to be "junk" DNA without any apparent function. But researchers now say it mediates the expression of FAAH, a gene that is part of the endocannabinoid system and is well-known for its involvement in pain, mood and memory. The team found that FAAH-OUT regulates the expression of FAAH, and that Cameron’s specific mutation causes it to be significantly turned down. As a result, her FAAH enzyme activity levels are reduced. Researchers found another 797 genes that were turned up and 348 genes that were turned down in Cameron. These included the WNT pathway that is associated with wound healing, with increased activity in the WNT16 gene that has been linked to bone regeneration. Two other key altered genes they found were BDNF, which has been linked to mood regulation, and ACKR3, which helps regulate opioid levels. Taken together, these gene changes may contribute to Cameron’s low levels of anxiety, fear and pain, researchers said. “The initial discovery of the genetic root of Jo Cameron’s unique phenotype was a eureka moment and hugely exciting, but these current findings are where things really start to get interesting,” said senior researcher James Cox , a professor with UCL Medicine. “By understanding precisely what is happening at a molecular level, we can start to understand the biology involved and that opens up possibilities for drug discovery that could one day have far-reaching positive impacts for patients,” Cox said in a university news release. Senior researcher Andrei Okorokov of UCL Medicine described the FAAH-OUT gene as just one small corner of a vast continent, which this study has begun to map. “As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation,” he said in the release. “As scientists it is our duty to explore and I think these findings will have important implications for areas of research such as wound healing, depression and more,” Okorokov added. The findings were published May 23 in the journal Brain . Sources University College London, news release, May 23, 2023 Posted May 2023