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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/28235973/endothelin-signaling-regulates-mineralization-and-posttranscriptionally-regulates-sost-in-tmob-cells-via-mir-126-3p
#1
Michael G Johnson, Kathryn Konicke, Jasmin Kristianto, Anne Gustavson, Rachel Garbo, Xiaohu Wang, Baozhi Yuan, Robert D Blank
Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST)...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28222387/baicalein-enhances-the-osteogenic-differentiation-of-human-periodontal-ligament-cells-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#2
Li-Jiao Chen, Bi-Bo Hu, Xin-Lian Shi, Man-Man Ren, Wen-Bin Yu, Sheng-Dan Cen, Rong-Dang Hu, Hui Deng
OBJECTIVE: Periodontium regeneration is one of the most important processes for periodontitis therapy. Human periodontal ligament cells (hPDLCs) play a vital role in the repair and regeneration of periodontal tissues. Our study aimed to investigated the mechanisms underlying the promotion of hPLDCs osteogenic differentiation by baicalein. DESIGN: hPDLCs were obtained from periodontal ligament (PDL) tissues by primary culture. The MTT assay was used to determine the growth curves of hPDLCs treated with different concentrations of baicalein (1...
February 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28219919/dickkopf-3-ablation-attenuates-the-development-of-atherosclerosis-in-apoe-deficient-mice
#3
Wen-Lin Cheng, Yang Yang, Xiao-Jing Zhang, Junhong Guo, Jun Gong, Fu-Han Gong, Zhi-Gang She, Zan Huang, Hao Xia, Hongliang Li
BACKGROUND: Dickkopf-3 (DKK3) is a negative regulator of the Wnt/β-catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis. METHODS AND RESULTS: Immunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice...
February 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28185033/stimulation-of-osteogenic-differentiation-by-saikosaponin-a-in-bone-marrow-stromal-cells-via-wnt-%C3%AE-catenin-pathway
#4
Weiqi Huang, Xiaoling Zheng, Xiaodong Yang, Shicai Fan
Saikosaponin-A (SA), a class of native compound with numerous biological activities, may exert protective effect against postmenopausal bone loss. However, it remains unknown whether SA regulates the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In this study, BMSCs were treated with various concentrations of SA to stimulate osteogenic differentiation over a 14-day period. Additionally, a canonical ovariectomized (OVX) mouse model was used to evaluate the effect of 3-month SA treatment in preventing postmenopausal osteoporosis...
February 9, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28174758/interferon-alpha-promotes-th1-response-and-epithelial-apoptosis-via-inflammasome-activation-in-human-intestinal-mucosa
#5
Anne Jarry, Florent Malard, Chantal Bou-Hanna, Guillaume Meurette, Mohamad Mohty, Jean-François Mosnier, Christian L Laboisse, Céline Bossard
BACKGOUND & AIMS: Several lines of investigation suggest that interferon (IFN) alpha can alter human intestinal mucosa homeostasis. These include the endogenous production of IFN alpha in celiac disease or inflammatory bowel diseases, as well as the occurrence of intestinal side effects of exogenous IFN alpha used as a therapeutic tool. Here, we present an ex vivo translational approach to investigate the effects of IFN alpha on the human normal intestinal mucosa, as well as its underlying mechanisms...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28173817/pigment-epithelium-derived-factor-alleviates-endothelial-injury-by-inhibiting-wnt-%C3%AE-catenin-pathway
#6
Shouyuan Ma, Shutong Yao, Hua Tian, Peng Jiao, Nana Yang, Ping Zhu, Shucun Qin
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) can induce endothelial injury and plays a vital role in the procession and development of atherosclerosis. Little is known regarding whether Wnt/β-catenin pathway is involved in ox-LDL-induced endothelial injury or whether it further promotes atherosclerosis via increased oxidative stress. This study aimed to investigate the role of Wnt/β-catenin pathway in ox-LDL-induced vascular endothelial injury and determine whether pigment epithelium-derived factor (PEDF) could alleviate ox-LDL-induced endothelial injury by inhibiting Wnt/β-catenin pathway...
February 7, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28163317/embelin-attenuates-adipogenesis-and-lipogenesis-through-activating-canonical-wnt-signaling-and-inhibits-high-fat-diet-induced-obesity
#7
Y Gao, J Li, X Xu, S Wang, Y Yang, J Zhou, L Zhang, F Zheng, X Li, B Wang
BACKGROUND: Recent studies suggest that Embelin, a natural plant extract might have the potential to prevent body weight gain in rats. However, the mechanisms involved remain to be elucidated. METHODS: Effects of Embelin on adipocyte differentiation and lipogenesis were studied in murine ST2 stromal cells and C3H10T1/2 mesenchymal cells. The mechanisms through which Embelin regulates adipogenic differentiation and lipogenesis were explored. The in vivo anti-obesity effects of Embelin in high-fat diet (HFD)-induced obesity mice and possible transcriptional impact were investigated...
February 6, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28154134/cdon-deficiency-causes-cardiac-remodeling-through-hyperactivation-of-wnt-%C3%AE-catenin-signaling
#8
Myong-Ho Jeong, Hyun-Ji Kim, Jung-Hoon Pyun, Kyu-Sil Choi, Dong I Lee, Soroosh Solhjoo, Brian O'Rourke, Gordon F Tomaselli, Dong Seop Jeong, Hana Cho, Jong-Sun Kang
On pathological stress, Wnt signaling is reactivated and induces genes associated with cardiac remodeling and fibrosis. We have previously shown that a cell surface receptor Cdon (cell-adhesion associated, oncogene regulated) suppresses Wnt signaling to promote neuronal differentiation however its role in heart is unknown. Here, we demonstrate a critical role of Cdon in cardiac function and remodeling. Cdon is expressed and predominantly localized at intercalated disk in both mouse and human hearts. Cdon-deficient mice develop cardiac dysfunction including reduced ejection fraction and ECG abnormalities...
February 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28153008/correlation-of-blood-bone-turnover-biomarkers-and-wnt-signaling-antagonists-with-as-dish-opll-and-oyl
#9
Chi-Chien Niu, Song-Shu Lin, Li-Jen Yuan, Lih-Huei Chen, Chuen-Yung Yang, An-Ni Chung, Meng-Ling Lu, Tsung-Ting Tsai, Po-Liang Lai, Wen-Jer Chen
BACKGROUND: Wnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL)...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#10
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28130569/histone-demethylase-utx-counteracts-glucocorticoid-deregulation-of-osteogenesis-by-modulating-histone-dependent-and-independent-pathways
#11
Feng-Sheng Wang, Wei-Shiung Lian, Mel S Lee, Wen-Tsan Weng, Ying-Hsien Huang, Yu-Shan Chen, Yi-Chih Sun, Shing-Long Wu, Pei-Chin Chuang, Jih-Yang Ko
: Excess glucocorticoid administration impairs osteogenic activities, which raises the risk of osteoporotic disorders. Epigenetic methylation of DNA and histone regulates the lineage commitment of progenitor cells. This study was undertaken to delineate the actions of histone lysine demethylase 6a (UTX) with regard to the glucocorticoid impediment of osteogenic differentiation. Osteogenic progenitor cells responded to supraphysiological glucocorticoid by elevating CpG dinucleotide methylation proximal to transcription start sites within Runx2 and osterix promoters and Wnt inhibitor Dickkopf-1 (Dkk1) expression concomitant with low UTX expression...
January 27, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28130402/connective-tissue-growth-factor-domain-4-amplifies-fibrotic-kidney-disease-through-activation-of-ldl-receptor-related-protein-6
#12
Bryce G Johnson, Shuyu Ren, Gamze Karaca, Ivan G Gomez, Cécile Fligny, Benjamin Smith, Ayla Ergun, George Locke, Benbo Gao, Sebastian Hayes, Scott MacDonnell, Jeremy S Duffield
Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction...
January 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28128299/lps-induced-inflammatory-response-is-suppressed-by-wnt-inhibitors-dickkopf-1-and-lgk974
#13
Jaewoong Jang, Yoonju Jung, Youngeun Kim, Eek-Hoon Jho, Yoosik Yoon
In this study, LPS-induced inflammatory responses in BEAS-2B human bronchial epithelial cells and human umbilical vein endothelial cell (HUVEC)s were found to be prevented by Dickkopf-1 (DKK-1), a secreted Wnt antagonist, and LGK974, a small molecular inhibitor of the Wnt secretion. LPS-induced IκB degradation and NF-κB nuclear translocation as well as the expressions of pro-inflammatory genes including IL-6, IL-8, TNF- α, IL-1β, MCP-1, MMP-9, COX-2 and iNOS, were all suppressed by DKK-1 and LGK974 in a dose-dependent manner...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28119179/the-chronic-kidney-disease-mineral-bone-disorder-ckd-mbd-advances-in-pathophysiology
#14
REVIEW
Keith A Hruska, Toshifumi Sugatani, Olga Agapova, Yifu Fang
The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical...
January 21, 2017: Bone
https://www.readbyqxmd.com/read/28107808/in-situ-release-of-vegf-enhances-osteogenesis-in-3d-porous-scaffolds-engineered-with-osterix-modified-adipose-derived-stem-cells
#15
Wan-Lin Xu, Hui-Shan Ong, Yun Zhu, Sheng-Wen Liu, Li-Min Liu, Kai-Hua Zhou, Zeng-Qi Xu, Jun Gao, Yan Zhang, Jin-Hai Ye, Wen-Jun Yang
Adipose-derived stem cells (ADSCs) can differentiate into various cell types and thus have great potential for regenerative medicine. Herein, rat ADSCs were isolated; transduced with lentiviruses expressing Osterix (Osx), a transcriptional factor essential for osteogenesis. Osx overexpression up-regulated key osteogenesis-related genes, such as special AT-rich binding protein 2, alkaline phosphatase, osteocalcin and osteopontin, at both the mRNA and protein levels. In addition, mineral nodule formation and alkaline phosphatase activity were enhanced in Osx-overexpressing ADSCs...
January 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28097491/small-interfering-rna-targeting-dickkopf-1-contributes-to-neuroprotection-after-intracerebral-hemorrhage-in-rats
#16
Zhihua Li, Xi Chen, Xiaoyang Zhang, Xiuhua Ren, Xuemei Chen, Jing Cao, Weidong Zang, Xianzhi Liu, Fuyou Guo
Excessive Dickkopf-1 (Dkk-1) plays a vital role in secondary brain injury following ischemic stroke and psychotic disease. However, it is unclear whether an increased expression of Dkk-1 occurred after intracerebral hemorrhage (ICH). The present study examined the potential role of Dkk-1 after ICH. ICH was induced by a single injection of autologous blood into the basal ganglia of rats. Dkk-1 protein levels in brain tissue and serum were detected by enzyme-linked immunosorbent assay after ICH. Rats were treated with small interfering RNA targeting Dkk-1 (siDkk-1) or vehicle following ICH...
January 17, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28054306/circulating-dickkopf-1-and-sclerostin-in-patients-with-paget-s-disease-of-bone
#17
Luca Idolazzi, Angelo Fassio, Gaia Tripi, Vania Braga, Ombretta Viapiana, Giovanni Adami, Maurizio Rossini, Davide Gatti
Paget disease of bone is a chronic metabolic bone disorder characterized by increased bone resorption and new bone formation. The aim of this study is defining the role of inhibitors of canonical Wnt/b-catenin signaling pathway in patients with Paget disease of bone. Scarce and contrasting results have been reported in literature. We studied 40 patients (15 females and 25 males) with radiological and scintigraphic evidence of Paget disease of bone and 40 healthy subjects matched by age and sex. N-propeptide of type I collagen, C-terminal telopeptide of type I collagen, sclerostin, and Dickkopf-related protein 1 (DKK1) were evaluated by blood samples in our laboratory...
January 5, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28039407/cryptosporidium-parvum-infection-attenuates-the-ex%C3%A2-vivo-propagation-of-murine-intestinal-enteroids
#18
Xin-Tian Zhang, Ai-Yu Gong, Yang Wang, Xiqiang Chen, Sheng-Yau S Lim, Courtney E Dolata, Xian-Ming Chen
Cryptosporidium, a ubiquitous coccidian protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces, is an important opportunistic pathogen for immunocompromised individuals and a common cause of diarrhea in young children in the developing countries. One of the pathological hallmarks of intestinal cryptosporidiosis is villous atrophy, which results in a shorter height of intestinal villi. Here, we investigated the effects of Cryptosporidium infection on intestinal epithelial growth, using an ex vivo model of intestinal cryptosporidiosis employing enteroids from mice...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/27959428/expression-pattern-of-dkk3-dickkopf-wnt-signaling-pathway-inhibitor%C3%A2-3-in-the-malignant-progression-of-oral-submucous-fibrosis
#19
Shanghui Zhou, Yun Zhu, Mubarak Mashrah, Xinyu Zhang, Zhijing He, Zhigang Yao, Chunye Zhang, Feng Guo, Yongjie Hu, Chenping Zhang
Oral squamous cell carcinoma (OSCC) is a common malignant neoplasm of the head and neck. Oral submucous fibrosis (OSF) is one of its pre-cancerous lesions; however, the key molecular events in the tumorigenesis of OSF remain elusive. Dickkopf WNT signaling pathway inhibitor 3 (DKK3) is one of the Wnt antagonists, and its downregulation and methylation have been reported in multiple malignancies, while no report of its expression in the carcinogenesis of OSF exists. In the present study, we investigated DKK3 expression at the protein and mRNA levels by immunochemical staining and semi‑quantitative RT-PCR in normal oral, OSF and OSCC tissues...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27864382/molecular-dynamics-of-dkk4-modulates-wnt-action-and-regulates-meibomian-gland-development
#20
Jian Sima, Yulan Piao, Yaohui Chen, David Schlessinger
Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, which is similar to that observed in Eda-ablated Tabby mice...
December 15, 2016: Development
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